Lipids Commons^™

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Improvement Of Memory Loss Through Dietary Intervention In The Assisted Living And Rehabilitative Settings, Alexander Swartz, Martin Forsberg

Stratford Campus Research Day

• The ketogenic diet is a popular, controversial diet that fuels the brain through beta-oxidation of fatty acids and production of ketone bodies, the most populous of which is betahydroxybutyrate (BHB).

• The ketogenic diet consists of 70-80% fats, 20-25% protein, and 5-10% carbohydrates.

• Medically, the ketogenic diet is utilized in patients with epilepsy and recommended by some physicians to improve general health through weight loss and insulin sensitivity.

• Key factors of neurodegeneration include glucose hypometabolism, oxidative damage, and neuroinflammation.

• Studies have shown that with ingestion of exogenous ketones alone, or endogenous ketonemia through a ketogenic diet, there is: …

Identification Of Lipid Species: Potential Biomarkers For Early Detection Of Hepatocellular Carcinoma, Kit Yee Leung, Kaylee Freitas

Undergraduate Research Symposium Posters

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is associated with cirrhosis. Poor survival rate of HCC is due to diagnosis of HCC at late stage.

A Quantitative Analysis Of The Efficacy Of Various Essential Oils Against The Sars Cov-2 Virus, Elizabeth Wagstaff, Chandrelyn Kraczek, Jack Brandon Lopez

Annual Research Symposium

A poster presentation and abstract for the Roseman Symposium. The project focuses on testing 3 essential oil blends and two disinfectants containing an essential oil blend against SARS CoV-2 in response to the COVID-19 pandemic. The project procedure involves plaque assays, disinfection, and neutralization techniques.

Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam

Undergraduate Research Posters

Tumors may induce tolerogenesis through signaling dendritic cells to produce tolerogenic molecules, such as indoleamine 2, 3-dioxygenase 1 (IDO1). Tumor-associated immunosuppression is associated with higher mortality in patients. Small interfering RNA (siRNA) has been shown to silence specific target genes in the target cell. The siRNA associated with these genes could support a gene knockdown of these immunosuppressors and reduce mortality. Delivery of these therapeutic nucleic acids is difficult in vivo because siRNA is easily broken down inside the cell and the bloodstream through present nucleases. Use of liposome polymers has been reviewed extensively in literature. YSK12-C4, a lipid nanoparticle …

Comparison Of Free Versus Encapsulated Drugs On 3t3 Differentiation, Simon H. Friedrich, Gabriel Volpe

Undergraduate Research Posters

The scope of this project was to design, synthesize and test targeted nanoparticles containing hydrophobic and hydrophilic drugs that promote browning in adipose tissue. For hydrophilic drugs the use of liposomes and their hydrophilic core is more useful than the PLGA nanoparticles which have hydrophobic cores. The inhibition of the FOXO1 pathway and modulation of autophagy in adipose tissue can promote browning of white adipose tissue, or an energy burning state where excess energy is burned as heat instead of stored in the cell. If successful, these drugs would offer an alternative treatment for obesity where changes to the patient's …

Design And Synthesis Of Α-Anomeric Diacetylene-Containing Glycosides As Photopolymerizable Molecular Gelators, Guijun Wang, Dan Wang, Anji Chen, Ifeanyi S. Okafor, Lalith Palitha Samankumara

Chemistry & Biochemistry Faculty Publications

Glycolipids with diacetylene functional groups are fascinating compounds with many practical uses. Among these, diacetylene-containing gelators are especially important because they can form photopolymerizable gels, which are useful stimuli-responsive materials. Inspired by the unique properties of diacetylene-containing gelators and to understand the structural influences especially the location of the diacetylene functional groups on the self-assembling properties, a series of 15 novel N-acetyl-d-glucosamine derivatives with the diacetylene functional group introduced at the anomeric position were designed and synthesized. The diacetylene function is attached to the sugar through α-glycosylation with the distance from the anomeric oxygen being varied from one, two, …

Sex Differences In The Association Of Sibship Size And Position In Sibship With Lipid Profile During Adolescence: A Cross-Sectional Study, Ali H. Ziyab, Mohammad Almari, Anwar Mohammad, Abdullah Al-Taiar, Wilfried Karmaus

Community & Environmental Health Faculty Publications

Background. Epidemiologic studies have reported associations of sibship size and position of the child in the sibship with multiple health outcomes, including adiposity and diabetes. However, little is known about sibling effects on lipids. Hence, this study sought to evaluate associations of the number of total, older, and younger siblings with lipid profile among adolescents. Methods. In a cross-sectional study among high school students aged 14 to 19 years, lipid levels were measured in capillary blood. Parents reported the number of siblings (total, older, and younger). Geometric means of lipids were calculated, and linear regression was used to estimate the …

Familial Hypercholesterolemia And Treatments, Alexis Steer

Williams Honors College, Honors Research Projects

My project will be a literature review regarding the genetic mutations associated with

familial hypercholesterolemia and the current available treatments.

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Targeting Plasma Membrane Phosphatidylserine Content To Inhibit Oncogenic Kras Function, Walaa E. Kattan

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). We therefore investigated whether reducing PM PtdSer content is sufficient to abrogate KRAS oncogenesis. Oxysterol-related binding proteins ORP5 and ORP8 exchange PtdSer synthesized in the ER for phosphatidylinositol-4-phosphate (PI4P) synthesized in the PM. We show that depletion of ORP5 or ORP8 reduced PM PtdSer levels, resulting in extensive mislocalization of KRAS from the PM. Concordantly, ORP5 or ORP8 depletion …

Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton

MSU Graduate Theses

Diethylene glycol monoethyl ether (DEGEE) is a promising solvent component in topical cream formulations due to its superior solubilizing abilities with certain active pharmaceutical ingredients. One of the goals of this study is to characterize the effects of pH on the physical and chemical stabilities of topical cream formulations containing particularly high concentrations of DEGEE by characterizing a full topical pH profile of 3.5 – 9.0. The second goal is to evaluate the presence, amount, and characteristics of lyotropic liquid crystals (LLCs), molecularly structured in a lamellar phase, in a model cream emulsion utilizing polarized light microscopy (PLM). The presence …

Complexation Of Glycoalkaloid Α- Tomatine With Sterols And Its Potential Application As An Anti-Cancer Drug, Bishal Nepal

Dissertations

Glycoalkaloids (GAs) are secondary metabolites found mostly in higher plant species and some marine invertebrates. They are known to form complexes with 3β-hydroxy sterols such as cholesterol causing membrane disruption. So far the visual evidence showcasing the complexes formed between glycoalkaloids and sterols has been mainly restricted to some earlier studies using Brewster angle microscopy. This study aimed to develop a method for topographic and morphological analysis of sterol-glycoalkaloid complexes. Langmuir-Blodgett (LB) transfer of monolayers comprising of glycoalkaloid tomatine, sterols, and lipids in varying molar ratios onto mica followed by AFM examination was performed. The AFM method used required minimal …

Lipoprotein-Induced Increases In Cholesterol And 7-Ketocholesterol Result In Opposite Molecular-Scale Biophysical Effects On Membrane Structure, Manuela A.A. Ayee, Irena Levitan

Faculty Work Comprehensive List

Under hypercholesterolemic conditions, exposure of cells to lipoproteins results in a subtle membrane increase in the levels of cholesterol and 7-ketocholesterol, as compared to normal conditions. The effect of these physiologically relevant concentration increases on multicomponent bilayer membranes was investigated using coarse-grained molecular dynamics simulations. Significant changes in the structural and dynamic properties of the bilayer membranes resulted from these subtle increases in sterol levels, with both sterol species inducing decreases in the lateral area and inhibiting lateral diffusion to varying extents. Cholesterol and 7-ketocholesterol, however, exhibited opposite effects on lipid packing and orientation. The results from this study indicate …

Crohn’S Disease And Omega 3: Can It Decrease Crp? A Literature Review, Ariana L. Vyvjala

Bachelors of Science in Nursing

The Crohn’s and Colitis foundation of America estimates that 70,000 Americans are diagnosed with inflammatory bowel disease (IBD) each year (2021). Crohn's disease is an inflammatory bowel disease characterized by periods of remission and exacerbation triggered by an increase in stress (Mackner et al., 2020). Patients can experience debilitating abdominal pain, diarrhea, fatigue, blood in the stool, and reduced appetite during an exacerbation period, all of which can lead to life-threatening complications (Mayo Clinic, 2020). In most cases, patients are diagnosed in their late teens or early adulthood years, and are prescribed anti-inflammatory drugs (Mayo Clinic, 2020). As there is …

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah

Seton Hall University Dissertations and Theses (ETDs)

Abstract

The emerging field of RNA nanotechnology has led to rapid advances in the applications of RNA in chemical biology, medicinal chemistry, and biotechnology. At the forefront of its utility is the ability to self-assemble multiple siRNAs into nanostructure formulations capable of targeting selected oncogenes and potentiating the gene therapy of malignant tumors. Self-assembled siRNA integrates multiple siRNAs within a single molecular platform for silencing multiple oncogenic mRNA targets with high precision and efficacy to potentially induce cancer cell apoptosis through the RNA interference (RNAi) pathway. Furthermore, the conjugation of siRNA self-assemblies with bio-active probes results in multi-functional theranostic (therapy+diagnostic) …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

Identification And Characterization Of Butyrate-Producing Species In The Human Gut Microbiome, Grace Maline

Theses/Capstones/Creative Projects

Inflammatory Bowel Diseases (IBD) including ulcerative colitis, indeterminate colitis, and Crohn’s disease are increasingly common conditions that places a high physical and financial burden on individuals and global healthcare systems. Though many treatments exist for these conditions, their unpredictable nature and causation make them difficult to manage across the variety of IBD patients. Additionally, many of these treatments come with undesirable side effects or modes of delivery. Therefore, it is worthwhile to explore the use of Short Chain Fatty Acids (SCFAs) such as butyrate whose affects in the human gut include decreased inflammation and decreased risk of colorectal cancer. As …

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Honors Program Projects

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus, …

Experimental And Computational Observations Of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association., Jasmin Federizon, Conrard Giresse Tetsassi Feugmo, Wei-Chiao Huang, Xuedan He, Kazutoyo Miura, Aida Razi, Joaquin Ortega, Mikko Karttunen, Jonathan F Lovell

Chemistry Publications

Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag); however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid …

Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe

Pharmacotherapy and Outcomes Science Publications

Aims: Platelet rich plasma (PRP) has been used in tissue repair to treat numerous inflammatory pathophysiologies. Recent studies have elucidated that the bioactive lipid fraction of PRP significantly contributes towards the resolution of inflammation. There has been great interest in how therapeutics could modulate the PRP lipidome to formulate a more pro-resolving matrix. Many of the pathways used to produce either pro-resolving or pro-inflammatory lipids are shared between ω-3 and ω-6 polyunsaturated fatty acids (PUFA). Here, we explored the separate and interacting effects acute exogenous ω-3 PUFA supplementation and aspirin had on the lipidome of PRP within 6 hours.

Methods: …

Impact Of Targeting Glycosylated Ceramides On Tumorigenic Properties, And Characterization Of Sphingolipids In Head And Neck Tumors, Katherine E. Hylton

Theses and Dissertations

Sphingolipids play a crucial role in signaling, membrane structure, and migration, making them important molecules in cancer development, metastasis, and drug resistance. While some sphingolipids have been associated with pro-apoptotic or pro-survival behaviors, the role of many sphingolipids in cancer remains poorly defined. Chapter 1 of this study investigated the impact of three enzymes that compose most of the ceramide to Lc3 ceramide pathway – UGCG, GBA, and B3GNT5 – and how their alteration impacts chemoresistance and basal membrane invasion in vitro. It was found that the CΒE-induced inhibition of GBA, which converts glucosylceramide to ceramide, has no effects on …

Interaction Between Genetic Risk Scores For Reduced Pulmonary Function And Smoking, Asthma And Endotoxin, Sinjini Sikdar, Annah B. Wyss, Mi Kyeong Lee, Thanh T. Hoang, Marie Richards, Laura E. Beane Freeman, Christine Parks, Peter S. Thorne, John L. Hankinson, David M. Umbach, Alison Motsinger-Reif, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene–environment interactions, but studies are few.

Methods We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case–control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV₁, …

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Pence-Boyce STEM Student Scholarship

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus …

Assessment Of The Use Of Low Molecular Weight Diblock Copolymers For The Formation Of Stable, Tunable Droplet Interface Bilayers, Joseph Tawfik

Masters Theses

This thesis presents the use of diblock copolymers, poly(butadiene)-b-poly(ethylene oxide) (PB_m PEO_n) and poly(isoprene)-b-poly(ethylene oxide) (PI_mPEO_n), as amphiphilic molecular building blocks for the formation of synthetic polymer bilayer membranes using the droplet interface bilayer (DIB) technique. The DIB technique makes use of the self-assembly of amphiphilic macromolecules along oil-water droplet interfaces that can then be physically connected for the construction of liquid supported macromolecular bilayers at the droplet interface. These bilayer membranes are capable of hosting both naturally occurring and synthetic protein channels. This technique has been used to form synthetic bilayer membranes …

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

In soft matter, thermal energy causes molecules to continuously translate and rotate, even in crowded environments, thereby impacting the spatial organization and function of most molecular assemblies, such as lipid membranes. Directly measuring the orientation and spatial organization of large collections (>3000 molecules μm⁻²) of single molecules with nanoscale resolution remains elusive. In this paper, we utilize SMOLM, single‐molecule orientation localization microscopy, to directly measure the orientation spectra (3D orientation plus “wobble”) of lipophilic probes transiently bound to lipid membranes, revealing that Nile red's (NR) orientation spectra are extremely sensitive to membrane chemical composition. SMOLM images resolve …