Lipids Commons^™

Glucagon-Like Peptide-1s Compared To Sulfonylureas In The Treatment Of Adults Diagnosed With Type Ii Diabetes Mellintus In Primary Care, Tracy Kirchner

Physician Assistant Scholarly Project Papers

Type II diabetes mellitus (T2DM) is a prevalent disease in our country. Bullard et al. (2018) report approximately 21 million adults have T2DM in the United States. “The total estimated cost of diagnosed diabetes in 2017 is $327 billion, including $237 billion in direct medical costs and $90 billion in reduced productivity” (Yang et al., 2018). Treatment of T2DM is individualized to each patient based on their co-morbidities, fiscal responsibility, and route of administration options. Sulfonylureas and Glucagon-like Peptide-1s (GLP-1) are two classes of antidiabetic drugs that are available for use as second line treatment options after metformin. This review …

Association Of Lowering Low-Density Lipoprotein Cholesterol With Contemporary Lipid-Lowering Therapies And Risk Of Diabetes Mellitus: A Systematic Review And Meta-Analysis, Victor Okunrintemi

All Publications

No abstract provided.

Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism And Lipid Droplet Formation, Brandon C. Farmer, Jude Kluemper, Lance A. Johnson

Physiology Faculty Publications

Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (APOE) and neurodegeneration. The E4 allele of APOE (E4) is the strongest genetic risk factor for the development of late onset Alzheimer’s disease (AD). Since both E4 carriers and individuals with AD exhibit a state of cerebral lipid dyshomeostasis, we hypothesized that APOE may play a role in regulating LD metabolism. We found that astrocytes expressing E4 accumulate significantly more and smaller LDs compared to E3 astrocytes. Accordingly, expression of perilipin-2, an essential LD protein component, was higher in E4 astrocytes. We then …

The Journey Of Implementing A Pediatric Essential Oil Program, Elizabeth Edmundson, Tiffany Kim

Nurse Presentations

Describes use of essential oil patches for specific indications with pediatric patients greater than 3 years old or greater than 20 kilograms. Lavender, peppermint, mandarin, or spearmint inhalation patches are used.

Glycosaminoglycan Mimetics For The Treatment Of Cancer And Lung Inflammation, Shravan Morla

Theses and Dissertations

Glycosaminoglycans (GAGs) are linear polysaccharides whose disaccharide building blocks consist of an amino sugar and either uronic acid or galactose. They are expressed on virtually all mammalian cells, usually covalently attached to proteins, forming proteoglycans. GAGs are highly negatively charged due to an abundance of sulfate and carboxylic acid groups, and are structurally very diverse, with differences arising from chain length, the type of monomeric units, the linkages between each monomeric unit, the position of sulfate groups, and the degree of sulfation. GAGs are known to interact with a multitude of proteins, impacting diverse physiological and pathological processes. In addition, …

Targeting Lipoprotein Biogenesis: Considerations Towards Antimicrobials, Toufic El Arnaout, Tewfic Soulimane

Articles

Decades have passed without approval of a new antibiotic class. Several companies have recently halted related discovery efforts because of multiple obstacles. One promising route under research is to target the lipoprotein maturation pathway in light of major recent findings and the virulence roles of lipoproteins. To support the future design of selective drugs, considerations and priority-setting are established for the main lipoprotein processing enzymes (Lgt, LspA, and Lnt) based on microbiology, biochemistry, structural biology, chemical design, and pharmacology. Although not all bacterial species will be similarly impacted by drug candidates, several advantages make LspA a top target to pursue …

Diuretic And Natriuretic Activity Of Faah Inhibition In The Renal Medulla: A Proposed Role Of Palmitoylethanolamide And Its Regulation By Renal Medullary Interstitial Cells, Sara Dempsey

Theses and Dissertations

Hypertension is a critical public health issue worldwide, and in the United States, it is the leading cause of heart disease, stroke, and kidney failure, contributing to more than 1,100 deaths per day. It is proposed that the renal medulla combats increased blood pressure by releasing a neutral lipid from the lipid droplets of medullary interstitial cells, termed medullipin, which induces diuresis- natriuresis and vasodepression. The renal medulla is enriched with fatty acid lipid ethanolamides including the endocannabinoid anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), along with their primary hydrolyzing enzyme fatty acid amide hydrolase (FAAH). Our lab is investigating …

Autotaxin-Lpa Signaling Contributes To Obesity-Induced Insulin Resistance In Muscle And Impairs Mitochondrial Metabolism, Kenneth D'Souza, Carine Nzirorera, Andrew M. Cowie, Geena P. Varghese, Purvi Trivedi, Thomas O. Eichmann, Dipsikha Biswas, Mohamed Touaibia, Andrew J. Morris, Vassilis Aidinis, Daniel A. Kane, Thomas Pulinilkunnil, Petra C. Kienesberger

Internal Medicine Faculty Publications

Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX^+/−) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. …

Mass Spectrometry Image Creator (Msic): Ion Mobility / Mass Spectrometry Imaging Workflow In Python, Stephen Creger, Julia Laskin, Daniela Mesa Sanchez

The Summer Undergraduate Research Fellowship (SURF) Symposium

Mass spectrometry (MS) is a powerful characterization technique that enables identification of compounds in complex mixtures. Acquiring mass spectra in a spatially-resolved manner (i.e. over a grid), allows the data to be used to generate images that show the spatial distribution and relative intensities of every compound in a sample. These images can be used to monitor and identify biomarkers, explore the metabolism of compounds within tissues, and much more. However, the limitations of mass spectrometry can result in ambiguous compound identifications. Another characterization tool, ion mobility spectrometry (IM) can be integrated into existing MS routines to address this problem; …

Endocannabinoid Metabolome Of Human Breast Milk, Adriana V. Gaitan Espinoza

LSU Doctoral Dissertations

Human breast milk (HBM) is an extremely complex yet fascinating biofluid tailored to meet an infant’s nutritional requirements for development. Amongst the nutrients present in HBM, the long-chain polyunsaturated fatty acids (LCPUFAs) are of high importance due to the pivotal role they play in infant cognitive and visual development, and growth. In addition, the LCPUFAs are precursors to endocannabinoids (EC) which are endogenous lipid mediators. EC exert metabolic responses including appetite and food intake regulation, and they have been identified to play a role in establishing the suckling response of the newborn that is needed to nurse. Thus, we aimed …

Psychological Well-Being And Restorative Biological Processes: Hdl-C In Older English Adults, Jackie Soo, Laura D. Kubzansky, Ying Chen, Emily S. Zevon, Julia K. Boehm

Psychology Faculty Articles and Research

Rationale

Psychological well-being is associated with better cardiovascular health, but the underlying mechanisms are unclear.

Objective

This study investigates one possible mechanism by examining psychological well-being's prospective association with lipid levels, focusing on high-density lipoprotein cholesterol (HDL-C).

Methods

Participants were 4757 healthy men and women ages ≥50 from the English Longitudinal Study of Ageing with clinical data from three times, three to five years apart. Psychological well-being was assessed at baseline using the Control, Autonomy, Satisfaction, and Pleasure scale; HDL-C, triglycerides, and total cholesterol were assayed from blood samples. Descriptive statistics and linear mixed models were used to examine associations …

Serum Lipidomics Of Bovine Paratuberculosis: Disruption Of Choline-Containing Glycerophospholipids And Sphingolipids, Paul L. Wood, Erdal Erol, Glen F. Hoffsis, Margaret Steinman, Jeroen Debuck

Veterinary Science Faculty Publications

Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2–4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle.

Methods: Serum lipidomics of control and M. avium subspecies paratuberculosis–infected cattle were performed utilizing high-resolution mass spectrometry.

Results: In …

Abcg5 And Abcg8: More Than A Defense Against Xenosterols, Shailendra B. Patel, Gregory A. Graf, Ryan E. Temel

Pharmaceutical Sciences Faculty Publications

The elucidation of the molecular basis of the rare disease, sitosterolemia, has revolutionized our mechanistic understanding of how dietary sterols are excreted and how cholesterol is eliminated from the body. Two proteins, ABCG5 and ABCG8, encoded by the sitosterolemia locus, work as obligate dimers to pump sterols out of hepatocytes and enterocytes. ABCG5/ABCG8 are key in regulating whole-body sterol trafficking, by eliminating sterols via the biliary tree as well as the intestinal tract. Importantly, these transporters keep xenosterols from accumulating in the body. The sitosterolemia locus has been genetically associated with lipid levels and downstream atherosclerotic disease, as well as …

Effects Of Mitochondrial Nadp+-Dependent Isocitrate Dehydrogenase Deficiency On Fructose-Induced Obesity In Mice, Allison Michelle Montalbano, Kaleigh Elizabeth Beane

Human Nutrition and Hospitality Management Undergraduate Honors Theses

Obesity prevalence in the United States continues to increase and is associated with health consequences such as type 2 diabetes, hypertension, atherosclerosis, and hyperlipidemia. Among many contributing factors to obesity, fructose may be one of the major reasons as it disrupts the antioxidant system thereby resulting in an accumulation of reactive oxidative species and leading to obese conditions. The enzyme, isocitrate dehydrogenase 2 (IDH2), reduces nicotinamide adenine dinucleotide phosphate from the TCA Cycle, hence might be implicated with not only energy metabolism but also cellular redox homeostasis. Therefore, the hypothesis was that IDH2 deficiency in mice would exacerbate hepatic lipid …

Increased Liver Tumor Formation In Neutral Sphingomyelinase-2-Deficient Mice, Liansheng Zhong, Ji Na Kong, Michael B. Dinkins, Silvia Leanhart, Zhihui Zhu, Stefka D. Spassieva, Haiyan Qin, Hsuan-Pei Lin, Ahmed Elsherbini, Rebecca Wang, Xue Jiang, Mariana N. Nikolova‑Karakashian, Guanghu Wang, Erhard Bieberich

Physiology Faculty Publications

Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a potential repressor for hepatocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed a marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with more than a 7-fold increase of C₁₆-ceramide, concurrent with upregulation of ceramide synthase 5. The fro/fro liver tumor, …

An Exome-Wide Sequencing Study Of Lipid Response To High-Fat Meal And Fenofibrate In Caucasians From The Goldn Cohort, Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis C. Frazier-Wood, Hemant K. Tiwari, Tushar Dave, Kathleen Ryan, Jose M. Ordovas, Robert J. Straka, Mary F. Feitosa, Paul N. Hopkins, Ingrid Borecki, Michael A. Province, Braxton D. Mitchell, Donna K. Arnett, Degui Zhi

Epidemiology and Environmental Health Faculty Publications

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial …

Bacterial Lps At The Immune Modulating Component In Juzen-Taiho-To, Diego Montenegro

Dissertations, Theses, and Capstone Projects

Juzen-taiho-to (JTT) is an immune-boosting herbal formulation with an ideal balance of safety and efficacy. For example, JTT is clinically used in Japan to stimulate the immunological functions of cancer patients undergoing chemotherapy and radiation. Although the clinical effects of JTT are recognized, the active compounds and mechanism of action are unknown. The studies conducted previously in our laboratory associated several phytosterols and plant glycolipids with the potent immunostimulatory activity of JTT: namely, β-sitosteryl β-D-glucoside (BSSG), glucocerebroside (GluCer), digalactosyldiacylglycerol (DGDG) and monogalactosyldiacylglycerol (MGDG). However, these compounds, when further purified, exhibited little or no immunostimulatory activity. This suggested that the immunostimulatory …

Dynamic Cycling Of T-Snare Acylation Regulates Platelet Exocytosis, Jinchao Zhang, Yunjie Huang, Jing Chen, Haining Zhu, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

Platelets regulate vascular integrity by secreting a host of molecules that promote hemostasis and its sequelae. Given the importance of platelet exocytosis, it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated with platelet membranes and redistributed into cholesterol-dependent lipid rafts when platelets are activated. Using metabolic labeling and hydroxylamine (HA)/HCl treatment, we showed that both contain thioester-linked acyl groups. Mass spectrometry mapping further showed that syntaxin-11 was modified on cysteine 275, 279, 280, 282, 283, and 285, and SNAP-23 was modified on cysteine 79, 80, 83, …

Novel Function Of Ceramide For Regulation Of Mitochondrial Atp Release In Astrocytes, Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B. Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D. Spassieva, Erhard Bieberich

Physiology Faculty Publications

We reported that amyloid β peptide (Aβ₄₂) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ₄₂ induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro-sphingosine …

The Role Of Ceramide In Neutrophil Elastase Induced Inflammation In The Lungs, Sophia Karandashova

Theses and Dissertations

Alterations to sphingolipid metabolism are associated with increased pulmonary inflammation, but the impact of inflammatory mediators, such as neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. NE is a protease associated CF lung disease progression, and can be found in up to micromolar concentrations in patient airways. While sphingolipids have been investigated in the context of CF, the focus has been on loss of cystic fibrosis transmembrane conductance regulator (CFTR) function. Here, we present a novel observation: oropharyngeal aspiration of NE increases airway ceramides in mice. Using a previously characterized mouse model of NE-induced inflammation, we demonstrate that NE …

Naturally Occurring 3rs, 7r, 11r-Phytanic Acid Suppresses In Vitro T-Cell Production Of Interferon-Gamma, Tomonori Nakanishi, Ibuki Motoba, Mayuko Anraku, Ryoji Suzuki, Yuto Yamaguchi, Laurie Erickson, Satoshi Kawahara

Hebrew Theological College Publications and Research

Background: Among the eight stereoisomers of phytanic acid (PA), the 3RS, 7R, 11R-isomer is naturally occurring and is present in foods and the human body. PA is considered to have possible health benefits in the immune system. However, it remains undetermined whether these effects are elicited by the 3RS, 7R, 11R-PA isomer, because previous studies used a commercially available PA whose isomer configuration is unknown. In this study, we synthesized a preparation of 3RS, 7R, 11R-PA, and investigated its in vitro immunomodulatory effects, especially the T-cell production of interferon (IFN)-γ, which is associated with various autoimmune diseases. This study …

The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, Julia Grzymkowski, Christopher J. Ehrhardt, Justin L. Poklis, Michelle R. Peace

Undergraduate Research Posters

There has been an increase in use of Traditional Chinese Medicine (TCM) in the United States because they are less expensive and believed to be more effective with less adverse effects in comparison to traditional pharmaceutics. Therefore, sales have increased in the US, despite articles and case studies demonstrating the dangers, such as injury and death, related to TCM, stemming from improper labelling, toxic contaminants, and, in some cases, the presence of pathogenic bacteria. The aim of this study was to perform a survival experiment to demonstrate the importance of proper herbal brewing technique and to conduct a molecular and …

Pde8 Is Expressed In Human Airway Smooth Muscle And Selectively Regulates Camp Signaling By Β 2 Ar-Ac6, Timothy B. Johnstone, Kaitlyn H. Smith, Cynthia J. Koziol-White, Fengying Li, Austin G. Kazarian, Maia L. Corpuz, Maya Shumyachter, Frederick J. Ehlert, Bianca E. Himes, Reynold A. Pannettieri Jr., Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Two cAMP signaling compartments centering around adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing ß2AR-AC6 and another containing E prostanoid receptors (EPR)-AC2. We hypothesized that different phosphodiesterase (PDE) isozymes selectively regulate cAMP signaling in each compartment. According to RNA-seq data, 18 of 24 PDE genes were expressed in primary HASM cells derived from age- and gender-matched donors with and without asthma. PDE8A was the third most abundant of the cAMP-degrading PDE genes, after PDE4A and PDE1A. Knockdown of PDE8A using shRNA evoked 2-fold greater cAMP responses to 1 DM forskolin in the presence of IBMX. …

Modification Of The Ribosome As Part Of The Adaptive Response To Oxidative Stress In Yeast, Jessica A Zinskie, Daniel Shedlovskiy, Ethan Gardner, Dimitri G Pestov, Natalia Shcherbik

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Living organisms are constantly exposed to a variety of environmental and internal stressors tha tare detrimental to their cellular physiology and viability. One such condition, oxidativestress, is caused by abnormal amounts of Reactive Oxygen Species (ROS) that can lead to damage to proteins, nucleic acids, and lipids. Although the mechanisms to neutralize ROS have been widely studied, the understanding of ROS‐mediated signaling for these mechanisms is rather incomplete and sparse. We have uncovered a previously undescribed phenomenon of yeast ribosomes to respond to elevated levels of ROS through a specific endonucleolytic cleavage of the 25S rRNA in the c‐loop of …

Serum Amyloid A3 Is A High Density Lipoprotein-Associated Acute-Phase Protein, Lisa R. Tannock, Maria C. De Beer, Ailing Ji, Preetha Shridas, Victoria P. Noffsinger, Laura Den Hartigh, Alan Chait, Frederick C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a family of acute-phase reactants. Plasma levels of human SAA1/SAA2 (mouse SAA1.1/2.1) can increase ≥ 1,000-fold during an acute-phase response. Mice, but not humans, express a third relatively understudied SAA isoform, SAA3. We investigated whether mouse SAA3 is an HDL-associated acute-phase SAA. Quantitative RT-PCR with isoform-specific primers indicated that SAA3 and SAA1.1/2.1 are induced similarly in livers (∼2,500-fold vs. ∼6,000-fold, respectively) and fat (∼400-fold vs. ∼100-fold, respectively) of lipopolysaccharide (LPS)-injected mice. In situ hybridization demonstrated that all three SAAs are produced by hepatocytes. All three SAA isoforms were detected in plasma of LPS-injected mice, although …

Prevention Of Renal Apob Retention Is Protective Against Diabetic Nephropathy: Role Of Tgf-Β Inhibition, Patricia G. Wilson, Joel C. Thompson, Meghan S. Yoder, Richard Charnigo, Lisa R. Tannock

Internal Medicine Faculty Publications

Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr^−/− mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect …

Roles Of Gabab, Muscarinic And Nicotinic Receptor Signaling In The Acquisition And Expression Of Fructose And Fat-Conditioned Flavor Preferences And Acquisition Of Quinine-Conditioned Flavor Avoidances In Rats, Francis M. Rotella

Dissertations, Theses, and Capstone Projects

In addition to increased intake of sweet solutions by mammals, learning, particularly classically-conditioned “Pavlovian-like” learning, also plays an important role. An orosensory conditioned flavor preference (CFP) can be elicited by pairing one novel flavor (conditioned stimulus, CS+) with a fructose solution and a second novel flavor (CS-) with a saccharin solution. Rats will prefer the CS+ flavor in a subsequent 2-bottle choice test with both flavors mixed in saccharin. Previous pharmacological analyses revealed that systemic administration of dopamine (DA) D1 and D2 as well as NMDA, but not opioid, receptor antagonists eliminated the acquisition (learning) of fructose-CFP. Further, expression of …

Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre

Electronic Theses and Dissertations

Acute kidney injury (AKI), resulting from cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves cell death pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results indicate that cisplatin-treated mice had increased levels of ceramide and hexosylceramide. Pre-treatment of mice with inhibitors of ceramide synthesis prevented accumulation of ceramide and hexosylceramide in the renal cortex and attenuated cisplatin-induced AKI. To determine the role of ceramide metabolism to hexosylceramides in kidney injury, we treated mice with an inhibitor of glycosphingolipid synthesis. Inhibition of glycosphingolipid synthesis attenuated the accumulation of the hexosylceramide and exacerbated ceramide accumulation in the …

Naturally-Derived Molecular Ensembles In Medicine, Materials Science And Evolutionary Biology: An Interdisciplinary Study, Silvio Panettieri

Dissertations, Theses, and Capstone Projects

The first chapter will introduce the work carried out in collaboration with the Govind laboratory at CCNY. Our quest was set forth to investigate the intimate relationship lying between chronic inflammation and tumor development. For at least the last fifteen years much research has been conducted on this topic; yet, the level of complexity arising from exceedingly interwoven biochemical pathways in mammals has resulted in slow advancements in this field. This is why we resorted to a simple yet powerful immunogenetic model organism, the fruit fly Drosophila melanogaster, in combination with the administration of the most common anti-inflammatory drug, …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …