Pharmacy and Pharmaceutical Sciences Commons^™

Impact Of A Culturally-Grounded And Interprofessional Approach To Managing Latino/Hispanic Patients At Risk For Or Diagnosed With Type 2 Diabetes Mellitus: A Pilot Study, Jahnavi Yalamanchili

University of the Pacific Theses and Dissertations

Background: Despite significant progress in diabetes research, there remain significant health disparities between Hispanic/Latino patients in the United States, particularly those with lower socioeconomic status, compared to non-Hispanic white patients. Previous studies have identified potential reasons behind these disparities, including the need for a multifaceted approach that addresses social determinants of health (SDOH) faced by patients. Social cognitive theory (SCT) stipulates that interventions that promote self-management by improving knowledge, self-efficacy, and problem-solving skills can be successful in improving health outcomes. However, there is a paucity of studies that have evaluated an interprofessional approach to providing culturally relevant care, in particular …

Impact Of Drug-Polymer Interactions On Stability In Simvastatin-Based Amorphous Solid Dispersions, Charina Lampa

University of the Pacific Theses and Dissertations

This study aimed to investigate the drug-polymer interactions between simvastatin (SIM) and three polymers [PVP-VA, HPMC-AS, and Soluplus® (SOL)] in amorphous solid dispersions (ASDs) prepared by hot melt extrusion (HME), and to understand the implications on physical stability. ASDs are of significant interest within the pharmaceutical industry for improving drug bioavailability. However, the amorphous nature of a drug in an ASD presents physical stability challenges. Utilizing novel applications of accessible tools such as ATR-FTIR or DSC aid in understanding the mechanisms of stabilization which are critical to the rational design of ASDs. ASDs were prepared using HME and were characterized …

Comprehensive, Evidence-Based, Consensus Guidelines For Prescription Of Opioids For Chronic Non-Cancer Pain From The American Society Of Interventional Pain Physicians (Asipp)., Laxmaiah Manchikanti, Adam M. Kaye, Nebojsa Nick Knezevic, James Giordano, Megan K. Applewhite, Alexander Bautista, Amol Soin, Susan K. Blank, Mahendra R. Sanapati, Jay Karri, Paul J. Christo, Alaa Abd-Elsayed, Alan D. Kaye, Aaron Calodney, Annu Navani, Christopher G. Gharibo, Michael Harned, Mayank Gupta, Mustafa Broachwala, Nalini Sehgal, Andrew Kaufman, Bradley Wargo, Daneshvari R. Solanki, Eric S. Hsu, Gerard Limerick, Allen Dennis, John R. Swicegood, Konstantin Slavin, Lee Snook, Ramarao Pasupuleti, Radomir Kosanovic, Rafael Justiz, Robert Barkin, Sairam Atluri, Shalini Shah, Vidyasagar Pampati, Standiford Helm Ii, Vahid Grami, Vicki Myckowiak, Vincent Galan, Vijay Singh, Vivek Manocha, Joshua A. Hirsch

School of Pharmacy Faculty Articles

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate …

Neuropharmacology Of Human [Tera2.Cl.Sp12] Stem Cell-Derived Neurons In Ultra-Long-Term Culture For Antiseizure Drug Discovery, Hamed Salmanzadeh, Ankita Poojari, Atefeh Rabiee, Benjamin D. Zeitlin, Robert F. Halliwell

School of Pharmacy Faculty Articles

Modeling the complex and prolonged development of the mammalian central nervous system in vitro remains a profound challenge. Most studies of human stem cell derived neurons are conducted over days to weeks and may or may not include glia. Here we have utilized a single human pluripotent stem cell line, TERA2.cl.SP12 to derive both neurons and glial cells and determined their differentiation and functional maturation over 1 year in culture together with their ability to display epileptiform activity in response to pro-convulsant agents and to detect antiseizure drug actions. Our experiments show that these human stem cells differentiate in vitro …

Moderate-Intensity Exercise Improves Mesenteric Arterial Function In Male Uc Davis Type-2 Diabetes Mellitus (Ucd-T2dm) Rats: A Shift In The Relative Importance Of Endothelium-Derived Relaxing Factors (Edrf), Md Rahatullah Razan, Said Amissi, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric …

Brivaracetam To Treat Partial Onset Seizures In Adults., Dustin Latimer, David Le, Evan P. Falgoust, Patrick Ingraffia, Alaa Abd-Elsayed, Elyse M. Cornett, Rupin Singh, Joohee Choi, Giustino Varrassi, Adam M. Kaye, Alan D. Kaye, Latha Ganti

School of Pharmacy Faculty Articles

PURPOSE OF REVIEW: Seizures are a hyperexcitable, and hypersynchronous imbalance between excitatory and inhibitory factors (E/I imbalance) in neurotransmission, and epilepsy is the recurrent manifestation of seizures within a reasonable time frame and without being attributable to a reversible cause. Brivaracetam is a derivative of the antiepileptic agent, levetiracetam, that is used as adjuvant therapy for focal onset seizures. It was approved by the FDA in 2016 and has shown promising results with minimal adverse effect reactions in clinical trials.

RECENT FINDINGS: Brivaracetam has been used in multiple clinical trials at various dosages in adults that have partial-onset seizures refractory …

Suvorexant, A Novel Dual Orexin Receptor Antagonist, For The Management Of Insomnia., Andrew H. Han, Carolin R. Burroughs, Evan P. Falgoust, Jamal Hasoon, Grace Hunt, Juyeon Kakazu, Tim Lee, Adam M. Kaye, Alan D. Kaye, Latha Ganti

School of Pharmacy Faculty Articles

PURPOSE OF REVIEW: The present investigation is a comprehensive review regarding the use of Suvorexant for insomnia treatment. It covers the background, pathophysiology, and significance of addressing insomnia, the pharmaceutical details of Suvorexant, and its safety, efficacy, and implications in treating insomnia. We further discuss Suvorexant's role in targeting insomnia with other comorbidities.

RECENT FINDINGS: Insomnia refers to poor quality and/or quantity of sleep. While there are many existing treatments such as benzodiazepines, melatonin agonists, TCAs, and atypical antipsychotics used to target various receptors involved in normal induction and maintenance of sleep, Suvorexant is an antagonist that specifically targets orexin …

Review Of Interventional Therapies For Refractory Pediatric Migraine., Jacquelin Peck, Justin Zeien, Megha Patel, Elyse M. Cornett, Amnon A. Berger, Jamal Hasoon, Hisham Kassem, Jai Won Jung, Giovanni F. Ramírez, Paola Fugueroa, Neil R. Singhal, Jaehong Song, Adam M. Kaye, Alan D. Kaye, Sarang S. Koushik, Natalie H. Strand, Latha Ganti

School of Pharmacy Faculty Articles

This is a review of the latest and seminal evidence in pediatric migraine. It covers the etiology and pathophysiology known today, and then will review treatment options, efficacy and safety, quality of data and indications. Though migraine is usually regarded as an infliction in adults, it is not uncommon in the pediatric population and affects up to 8% of children. Children may experience migraine differently than adults, and present not only with headache but also frequent gastrointestinal symptoms. They are frequently shorter in duration than in adults. Traditional migraine treatment in adults is less effective in children. In this population, …

Role Of Cysteine Redox State In Altering The Epithelial-Mesenchymal Transition In Lung Cancer, Md Anisur Rahman

University of the Pacific Theses and Dissertations

Epithelial-mesenchymal transition is a process by which cancer cells increase their capability for metastasis. EMT involves conversion of epithelial cells into a mesenchymal phenotype which makes cancer cells more invasive and motile. Lung cancer has the highest mortality rate among different types of cancers globally. Lung cancer exists in various types, the most prevalent of which is non-small cell lung cancer (NSCLC). Several factors, including oxidative stress, can induce EMT in cancer cells. However, the mechanism of how reactive oxygen species (ROS)-induced changes in cysteine redox state affect EMT remains elusive. Our studies aim to understand this mechanism by inducing …

Investigating Bzip Recognition Of Dna Sequences Through A Knob-Socket Perspective, Aaron Tran

University of the Pacific Theses and Dissertations

To investigate whether higher order packing interactions confer protein-DNA specificity, a modified Knob-Socket (KS) model was used to analyze the interface of bZIP-DNA crystal structures. The KS analysis identified a nine-residue quadripartite recognition core consisting of four contiguous KS pockets P1, P2, N3, and N4 that each pack one of the four DNA half-site bases in the target sequence. Only one base per base pair packs, and these interactions are split across the DNA strands: the first two positive strand positions 1p and 2p pack into P1 and P2 while the last two negative strand positions 3n and 4n pack …

Evaluation Of Human Stem Cell-Derived Neurons In 2d And 3d Cultures For Neurodevelopmental Studies, Epilepsy Disease Modeling And Drug Discovery, Hamed Salmanzadeh-Dozdabi

University of the Pacific Theses and Dissertations

Human stem cells have revolutionized the study of early neural development, offering a powerful tool to investigate the complex processes involved in the formation of the nervous system. In this study, the human pluripotent stem cell line, TERA2.cl.SP12, was utilized to derive neuroglial cells and to determine their differentiation and functional maturation up to one year in culture; this model was then investigated as a new tool for the study of neurodevelopmental toxicity, for seizure modeling and as a screening method for the investigation of new anticonvulsants. Immunocytochemistry experiments determined that non-differentiated cells expressed the stem cell marker Oct-3/4 and, …

Targeting Ribonucleotide Reductase For Breast Cancer Treatment, Nahid Sultana

University of the Pacific Theses and Dissertations

Breast cancer is the second most common type of cancer in the world. Hormone receptor (HR) positive breast cancer (BC) is a prevalent disease accounting for approximately 2 million new cases globally. Almost 70-80% of breast cancer patients are women with a positive score for the estrogen receptor (ER). Triple-negative breast cancer (TNBC) which have a negative score for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) is considered an aggressive histological breast cancer subtype with limited treatment options.Frequently, doxorubicin (DOXO)-based chemotherapy is utilized in this patient population due to the lack of …

Interactions 2022, Thomas J. Long School Of Pharmacy

Interactions

In each issue of Interactions, the School’s annual magazine you will find stories about students, faculty and alumni from each of our disciplines. Learn about the ways our students, faculty and alumni are impacting their communities through health care outreach. Read about their research and how they are contributing to advances in patient care. Meet our Alumni of the Year and get to know our faculty.

Novel Designer Benzodiazepines: Comprehensive Review Of Evolving Clinical And Adverse Effects., Amber N. Edinoff, Catherine A. Nix, Amira S. Odisho, Caroline P. Babin, Alyssa G. Derouen, Salim C. Lutfallah, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4

17Β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation Of Mesenteric Arteries In Ovariectomized Uc Davis Type 2 Diabetes Mellitus Rats In Prediabetic State, Md Rahatullah Razan, Farjana Akther, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhibited a greater vascular dysfunction than males. Thus, the aim of this study was to investigate whether the female sex hormone, estrogen preserves mesenteric arterial vasorelaxation in UCD-T2DM female rats at an early prediabetic state. Age-matched female Sprague Dawley and prediabetic (PD) UCD-T2DM rats were ovariectomized (OVX) and subcutaneously implanted …

Methamphetamine Use: A Narrative Review Of Adverse Effects And Related Toxicities., Amber N. Edinoff, Sarah E. Kaufman, Keionne M. Green, Daniel A. Provenzano, Jesse Lawson, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Methamphetamine has been labeled "America's most dangerous drug" and has received significant public health attention. Stimulant addiction and tolerance are heavily documented in the literature; increasingly larger doses maintain euphoria in short time periods to withstand stimulant tolerance. Stimulant deaths are high in the United States and abroad. Between 2013 and 2019, deaths related to methamphetamine use quadrupled from 3,616 to 16,127. Methamphetamine use increased four-fold from 2015 to 2016. Due to this increase in methamphetamine use and its associated medical complications, the mortality rate associated with methamphetamine use has doubled over the past ten years. Cardiopulmonary symptoms include chest …

Selective Serotonin Reuptake Inhibitors And Associated Bleeding Risks: A Narrative And Clinical Review., Amber N. Edinoff, Keerthiga Raveendran, Marc A. Colon, Bennett H. Thomas, Katie A. Trettin, Grace W. Hunt, Adam M. Kaye, Elyse M. Cornett, Alan David Kaye

School of Pharmacy Faculty Articles

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects …

Viloxazine, A Non-Stimulant Norepinephrine Reuptake Inhibitor, For The Treatment Of Attention Deficit Hyperactivity Disorder: A 3 Year Update., Hannah W. Haddad, Paul B. Hankey, Jimin Ko, Zahaan Eswani, Pravjit Bhatti, Amber N. Edinoff, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Current treatment options for ADHD include pharmacological treatment (stimulants, non-stimulants, anti-depressants, anti-psychotics), psychological treatment (behavioral therapy with or without parent training, cognitive training, neurofeedback), and complementary and alternative therapies (vitamin supplementation, exercise). Central nervous system (CNS) stimulants are the primary pharmacological therapy used in treatment; however, these stimulant drugs carry a high potential for abuse and severe psychological/physical dependence. Viloxazine, a non-stimulant medication without evidence of drug dependence, is a selective norepinephrine reuptake inhibitor that has historically been prescribed as an anti-depressant medication. The extended-release (ER) form …

Buprenorphine And Its Formulations: A Comprehensive Review., Salomon Poliwoda, Nazir Noor, Jack S. Jenkins, Cain W. Stark, Mattie Steib, Jamal Hasoon, Giustino Varrassi, Ivan Urits, Omar Viswanath, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with …

Midazolam Nasal Spray To Treat Intermittent, Stereotypic Episodes Of Frequent Seizure Activity: Pharmacology And Clinical Role, A Comprehensive Review., Elyse M. Cornett, Meskerem A. Nemomsa, Bailey Turbeville, Matthew A. Busby, Jessica S. Kaye, Aaron J. Kaye, Joohee Choi, Giovanni F. Ramírez, Giustino Varrassi, Adam M. Kaye, Alan David Kaye, James Wilson, Latha Ganti

School of Pharmacy Faculty Articles

An intranasal formulation of midazolam, Nayzilam, has been FDA-approved to treat intermittent, stereotypic episodes of frequent seizure activity. Nayzilam is easy to administer and can quickly treat seizures that occur outside of the hospital. The intra-nasal route of administration allows non-medical personal to administer the drug which makes it more accessible and user-friendly in the event of a seizure. Many studies have indicated quick cessation of seizures with Nayzilam compared to rectal diazepam, which has been the standard of care treatment. Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative …

Phenothiazines And Their Evolving Roles In Clinical Practice: A Narrative Review., Amber N. Edinoff, Grace Armistead, Christina A. Rosa, Alexandra Anderson, Ronan Patil, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Phenothiazines, a diverse class of drugs, can be used to treat multiple mental health and physical conditions. Phenothiazines have been used for decades to treat mental illnesses, including schizophrenia, mania in bipolar disorder, and psychosis. Additionally, these drugs offer relief for physical illnesses, including migraines, hiccups, nausea, and vomiting in both adults and children. Further research is needed to prove the efficacy of phenothiazines in treating physical symptoms. Phenothiazines are dopaminergic antagonists that inhibit D2 receptors with varying potency. High potency phenothiazines such as perphenazine are used to treat various psychiatric conditions such as the positive symptoms of schizophrenia, the …

Aduhelm, A Novel Anti-Amyloid Monoclonal Antibody, For The Treatment Of Alzheimer's Disease: A Comprehensive Review., Hannah W. Haddad, Garett W. Malone, Nicholas J. Comardelle, Arielle E. Degueure, Salomon Poliwoda, Rachel J. Kaye, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Alzheimer's disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in …

Rimegepant For The Treatment Of Migraine., Amnon A. Berger, Ariel Winnick, Austin H. Carroll, Alexandra Welschmeyer, Nathan Li, Marc Colon, Antonella Paladini, Giovanni F. Ramírez, Jamal Hasoon, Elyse M. Cornett, Jaehong Song, Giustino Varrassi, Adam M. Kaye, Alan David Kaye, Latha Ganti

School of Pharmacy Faculty Articles

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide …

The Combinatory Effects Of Pediatric Obesity And Ontogeny On Monocarboxylate Transporter Expression In Tissues Of Drug Disposition, Michael Ng

University of the Pacific Theses and Dissertations

Proton-coupled and sodium-dependent monocarboxylate transporters are encoded by the SLC16A and SLC5A gene family of solute carriers, and are responsible for the transport of essential nutrients such as L-lactate, pyruvate, and ketone bodies. Basigin, or CD147, acts as an ancillary protein for MCT1 and MCT4, and is involved in membrane surface expression of transporters. MCT's are also involved in the shuttling of monocarboxylic xenobiotics across cell membranes, including the drugs valproate and gamma hydroxybutyrate. MCT’s are also important for normal mammalian development, particularly during embryogenesis and early neonatal life. Previous studies have shown that ketogenic diets increase MCT expression in …

Clinically Relevant Drug Interactions With Monoamine Oxidase Inhibitors., Amber N. Edinoff, Connor R. Swinford, Amira S. Odisho, Caroline R. Burroughs, Cain W. Stark, Walid A. Raslan, Elyse M. Cornett, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Monoamine oxidase inhibitors (MAOI) are a class of drugs that were originally developed for the treatment of depression but have since been expanded to be used in management of affective and neurological disorders, as well as stroke and aging-related neurocognitive changes. Ranging from irreversible to reversible and selective to non-selective, these drugs target the monoamine oxidase (MAO) enzyme and prevent the oxidative deamination of various monoamines and catecholamines such as serotonin and dopamine, respectively. Tyramine is a potent releaser of norepinephrine (NE) and is found in high concentrations in foods such as aged cheeses and meats. Under normal conditions, NE …

Incorporating Glutamic Acid-Valine-Citrulline Linker In Trifunctional Molecules Targeting Psma Ensures Enhanced Stability, Safety, And Efficacy In Mouse Model Of Prostate Cancer, Toufiq Ul Amin

University of the Pacific Theses and Dissertations

This project describes the development of a new antitumor therapeutic platform that combines the benefits of small-molecule drug conjugates (SMDCs) and antibody drug conjugates (ADCs). Valine-citrulline (VCit) dipeptide linkers are popular cathepsin B cleavable ADC linkers. Due to its instability in mouse serum, translating efficacy data from mouse to human is more difficult. It has been reported that replacing the VCit linker with glutamic acid-valine-citrulline (EVCit) improves ADC stability in mouse serum. The effect of the EVCit linker on the stability of SMDCs has not been reported so far. In a xenograft mouse model of prostate cancer, we found that …

Investigation Of Cdk8 Inhibitor Q-12 Effects On Cdk8 And Cdk8 Substrates In Triple Negative Breast Cancer Cell Line Mda-Mb-468, Shengxi Li

University of the Pacific Theses and Dissertations

Cyclin-dependent kinases (CDKs) and cyclins (Cyclins) are the core molecules in the regulation mechanism of the entire cell cycle. Cell cycle dysregulation is a common feature of human cancers, and inhibitors of cyclin-dependent kinases (CDKs) play a crucial role in cell cycle control and are one of the most promising areas of cancer therapy. We aspired to use our cyclin-dependent kinase 8 (CDK8) inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer (TNBC) and colorectal cancer cell lines …

Optimization Of The Structure Of Ttr Ligands For Half-Life Extension (Tlhe), Guanming Jiang

University of the Pacific Theses and Dissertations

Many potential therapeutic agents face challenges for their clinical development due to short circulation half-life. As a result, prolonging the half-life of therapeutic drugs in circulation while preserving their hydrophilicity and small size will be a key step toward more effective and safe pharmacological molecules. Our lab developed a new approach for enhancing the safety and efficacy of therapeutic agents. By endowing therapeutic agents with a hydrophilic small molecule (a derivative of the clinical candidate, AG10) which reversibly binds to the serum protein transthyretin (TTR), the half-life of the therapeutic agent should be extended by binding to the TTR in …

Expression Of Mouse Full-Length Aryl Hydrocarbon Receptor And Human Aryl Hydrocarbon Receptor Ligand Binding Domain In Pichia Pastoris, Yiyuan Wang

University of the Pacific Theses and Dissertations

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates biological responses to planar aromatic hydrocarbon. AHR activates gene transcription by binding to its corresponding enhancer with its partner-aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, this receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450. AHR exists widely in body tissues and affects bioactivation of carcinogenic compounds, T cell differentiation, fatty acid synthesis, cell proliferation, hematopoietic stem cell differentiation, respiratory reactivity, and insulin sensitivity. Although the precise mechanism illustrating the endogenous AHR function remains unclear, there has been intense interest in exploring AHR as a …

Optimizing The Human Aryl Hydrocarbon Receptor (Hahr) Expression In Pichia Pastoris, Junyu Qian

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a transcription factor which heterodimerizes with the aryl hydrocarbon receptor nuclear translocator (Arnt) to regulate downstream gene transcription. For the purpose of studying the crystal structure of human aryl hydrocarbon receptor (hAHR), it is essential to obtain abundant amount of pure recombinant protein.Basing on the benefits of using P. pastoris system to produce recombinant protein, including appropriate folding, secretion of interest proteins to the external environment of the cell, and easier purification process of protein due to the its limited production of endogenous secretory proteins [1], our lab chose P. pastoris yeast as the …