Chemicals and Drugs Commons^™

Effects Of Dietary Phytoestrogens On Spermatogenesis And Male Reproductive Tract In Mice, Trenton A. Dalm

Masters Theses

Increases in infertility over the past 50 years are linked to environmental exposures to endocrine disrupting chemicals (EDCs). One type of EDC is phytoestrogens, commonly found in soy-based diets and foods such as cauliflower, tofu, and broccoli. Phytoestrogens may bind estrogen receptors and have positive or negative effects on receptor signaling. The developing male reproductive tract is potentially susceptible to endocrine disruptors leading to changes in adult reproductive function and possibly infertility. We hypothesized that dietary phytoestrogen exposure would have a dose dependent effect with the high diet yielding the lowest sperm count and worst performance compared to the medium …

Probing Conformational Landscapes Of Binding And Allostery In The Sars-Cov-2 Omicron Variant Complexes Using Microsecond Atomistic Simulations And Perturbation-Based Profiling Approaches: Hidden Role Of Omicron Mutations As Modulators Of Allosteric Signaling And Epistatic Relationships, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we systematically examine the conformational dynamics, binding and allosteric communications in the Omicron BA.1, BA.2, BA.3 and BA.4/BA.5 spike protein complexes with the ACE2 host receptor using molecular dynamics simulations and perturbation-based network profiling approaches. Microsecond atomistic simulations provided a detailed characterization of the conformational landscapes and revealed the increased thermodynamic stabilization of the BA.2 variant which can be contrasted with the BA.4/BA.5 variants inducing a significant mobility of the complexes. Using the dynamics-based mutational scanning of spike residues, we identified structural stability and binding affinity hotspots in the Omicron complexes. Perturbation response scanning and network-based mutational …

Effects Of Environmental Pollutants On Liver Disease: Role Of The Gut-Liver Axis., Ngozi Victoria Adiele

Electronic Theses and Dissertations

Polychlorinated biphenyls (PCBs) and polystyrene (PS) microplastics are environmental pollutants associated with various diseases including toxicant associated fatty liver disease (TAFLD). Previously, exposure to Aroclor 1260 (a PCB mixture) has been shown to exacerbate TAFLD, partly through Aroclor 1260 induced gut dysbiosis. Studies has also demonstrated that PS exposure alters gut microbiome composition and induced obesity. However, the effects of Aroclor 1260 on the gut and the effects of PS on the liver are still understudied. Therefore, we hypothesize that environmental pollutants will disrupt the gut-liver axis through changes in gut and its microbiome as well as changes in liver …

Studying The Stability Of Collagen/Heparin Coatings To Be Used In Cell Therapy Applications, Gavin Mussino

Biological Sciences Undergraduate Honors Theses

This honors thesis aims to investigate the reusability and performance of cell coatings for cell therapy applications. Cell therapy, which involves the use of human cells to repair or replace damaged tissues, holds immense potential for medical advancements. However, ensuring the survival and functionality of transplanted cells remains a significant challenge. We focused on studying the effectiveness of coatings applied to cells for improved cell growth and viability. The research project involved the preparation of the coatings using a layer-by-layer method and the subsequent seeding of cells. The coated cells were then subjected to a series of experiments to assess …

Exogenous Exposure To Dihydroxyacetone Mimics High Fructose Induced Oxidative Stress And Mitochondrial Dysfunction, Raj Mehta

Honors Theses

Dihydroxyacetone (DHA) is a three-carbon sugar that is the active ingredient in sunless tanning products and a by-product of electronic cigarette (e-cigarette) combustion. Increased use of sunless tanning products and e-cigarettes has elevated exposures to DHA through inhalation and absorption. Studies have confirmed that DHA is rapidly absorbed into cells and can enter into metabolic pathways following phosphorylation to dihydroxyacetone phosphate (DHAP), a product of fructose metabolism. Recent reports have suggested metabolic imbalance and cellular stress results from DHA exposures. However, the impact of elevated exposure to DHA on human health is currently under-investigated. We propose that exogenous exposures to …

July / August 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the July & August 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

Effect Of Biological Variation In Hba1c And Blood Glucose On The Diagnosis Of Prediabetes, James M. Hempe, Shengping Yang, Daniel S. Hsia

School of Medicine Faculty Publications

Introduction: People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI. Methods: Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self-reported diabetes. HGI was calculated as the difference between a participant's observed HbA1c and a predicted HbA1c where predicted HbA1c = 0.024 FPG + 3.1. Participants were divided into low (HGI < −0.15%), moderate (HGI −0.15% to +0.15%) and high (HGI > +0.15%) HGI subgroups. Results: The prevalence of prediabetes was 42.4% based on …

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …

Assessment Of Personal Care Product Use And Perceptions Of Use In A Sample Of Us Adults Affiliated With A University In The Northeast, Adana A. M. Llanos, Amber Rockson, Kylie Getz, Patricia Greenberg, Eva Portillo, James A. Mcdonald, Dede K. Teteh, Justin Villasenor, Carolina Lozada, Jamirra Franklin, Vaishnavi More, Zorimar Rivera-Núñez, Carolyn W. Kinkade, Emily S. Barrett

Health Sciences and Kinesiology Faculty Articles

Evidence supports unequal burdens of chemical exposures from personal care products (PCPs) among some groups, namely femme-identifying and racial and ethnic minorities. In this study, we implemented an online questionnaire to assess PCP purchasing and usage behaviors and perceptions of use among a sample of US adults recruited at a Northeastern university. We collected PCP use across seven product categories (hair, beauty, skincare, perfumes/colognes, feminine hygiene, oral care, other), and behaviors, attitudes, and perceptions of use and safety across sociodemographic factors to evaluate relationships between sociodemographic factors and the total number of products used within the prior 24–48 h using …

The Structural Characterization And Bioactivity Assessment Of Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Caraway (Carum Carvi) Seeds, Taibah Aldakhil, Saud O. Alshammari, Bushra Siraj, Bishoy El-Aarag, Shamshad Zarina, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the folk medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein–ligand complex interactions through docking studies. We also evaluated nsLTP1 in vitro cytotoxic …

Calcium Carbonate As A Potential Intervention To Prevent Labor Dystocia: Narrative Review Of The Literature, Sabahat Raees, Marie Forgie, Rita Mitchell, Emily Malloy

Journal of Patient-Centered Research and Reviews

Anecdotally, there are attestations from clinicians of calcium carbonate being used successfully for laboring people experiencing labor dystocia. The goal of this narrative review was to provide a synopsis of pertinent literature on calcium use in obstetrics to explore the potential benefit of calcium carbonate as a simple and low-cost intervention for prevention or treatment of labor dystocia. To answer how calcium and carbonate physiologically contribute to myometrium contractility, we conducted a literature search of English-language peer-reviewed articles, with no year limitation, consisting of the keywords “calcium,” “calcium carbonate,” “calcium gluconate,” “pregnancy,” “hemorrhage,” and variations of “smooth muscle contractility” and …

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …

Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …

Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti

School of Graduate Studies Faculty Publications

Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Proteomic Profiling Of Extracellular Vesicles Isolated From Plasma And Peritoneal Exudate In Mice Induced By Crotalus Scutulatus Scutulatus Crude Venom And Its Purified Cysteine-Rich Secretory Protein (Css-Crisp), Armando Reyes, Joseph D. Hatcher, Emelyn Salazar, Jacob Galan, Anton Iliuk, Elda E. Sanchez, Montamas Suntravat

School of Medicine Publications

Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in …

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun

School of Medicine Faculty Publications

Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …

Not A Box Of Nuts And Bolts: Distribution Channels For Specialty Drugs?, Liang Xu, Vidya Mani, Hui Zhao

Research Collection Lee Kong Chian School Of Business

One of the most important trends in the pharmaceutical industry is the rapid growth of specialty drugs. Specialty drugs, mostly bio based, tend to be high risk, high priced, and more regulated than traditional drugs, resulting in unprecedented challenges in distribution. Such challenges lead to the emergence of specialty distributors (SDs), which, compared with traditional wholesalers (WSs), represent a more controlled channel and carry a smaller variety of drugs. Due to the risky nature of specialty drugs, manufacturers must consider the trade-off between access and control in determining whether to use SDs (partially or exclusively). Using a unique dataset assembled …