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Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari 2019 Chapman University

Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C20 hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(bAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was ...


The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth LeBegue 2019 University of South Carolina

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to ...


The Single Mitochondrion Of The Kinetoplastid Parasite Crithidia Fasciculata Is A Dynamic Network., John DiMaio, Gordon Ruthel, Joshua J. Cannon, Madeline F. Malfara, Megan L. Povelones 2018 The Pennsylvania State University

The Single Mitochondrion Of The Kinetoplastid Parasite Crithidia Fasciculata Is A Dynamic Network., John Dimaio, Gordon Ruthel, Joshua J. Cannon, Madeline F. Malfara, Megan L. Povelones

Department of Bioscience Technologies Faculty Papers

Mitochondria are central organelles in cellular metabolism. Their structure is highly dynamic, allowing them to adapt to different energy requirements, to be partitioned during cell division, and to maintain functionality. Mitochondrial dynamics, including membrane fusion and fission reactions, are well studied in yeast and mammals but it is not known if these processes are conserved throughout eukaryotic evolution. Kinetoplastid parasites are some of the earliest-diverging eukaryotes to retain a mitochondrion. Each cell has only a single mitochondrial organelle, making them an interesting model for the role of dynamics in controlling mitochondrial architecture. We have investigated the mitochondrial division cycle in ...


Gamifying Accelerometer Use Increases Physical Activity Levels Of Sedentary Office Workers, Allene L Gremaud, Lucas J Carr, Jacob E Simmering, Nicholas J Evans, James F Cremer, Alberto M Segre, Linnea A Polgreen, Philip M Polgreen 2018 University of Iowa

Gamifying Accelerometer Use Increases Physical Activity Levels Of Sedentary Office Workers, Allene L Gremaud, Lucas J Carr, Jacob E Simmering, Nicholas J Evans, James F Cremer, Alberto M Segre, Linnea A Polgreen, Philip M Polgreen

Department of Health and Human Physiology Publications

BACKGROUND: Sedentary work is hazardous. Over 80% of all US jobs are predominantly sedentary, placing full-time office workers at increased risk for cardiovascular and metabolic morbidity and mortality. Thus, there is a critical need for effective workplace physical activity interventions. MapTrek is a mobile health platform that gamifies Fitbit use for the purpose of promoting physical activity. The purpose of this study was to test the efficacy of MapTrek for increasing daily steps and moderate-intensity steps over 10 weeks in a sample of sedentary office workers.

METHODS AND RESULTS: Participants included 146 full-time sedentary office workers aged 21 to 65 ...


Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen 2018 University of Nebraska-Lincoln

Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen

Chemical and Biomolecular Engineering -- All Faculty Papers

In this study, heparin-loaded poly-ε-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was ...


Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti 2018 University of Massachusetts Medical School

Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti

GSBS Dissertations and Theses

Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.

We established that cholesterol-conjugated siRNAs passively associate ...


Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related Toxicities, Ashvin Jaiswal 2018 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related Toxicities, Ashvin Jaiswal

UT GSBS Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of ...


Different Methodologies To Characterize And Diagnose Sickle Cell Disease In Both Developed And Developing Nations, Mohammed AlHarbi 2018 Dominican University of California

Different Methodologies To Characterize And Diagnose Sickle Cell Disease In Both Developed And Developing Nations, Mohammed Alharbi

Graduate Master's Theses, Capstones, and Culminating Projects

Sickle cell disease (SCD) is a genetic blood disorder that causes the RBC to become sickle shaped due to a mutation in the β-globin gene encoding the protein hemoglobin. This disease causes reduced oxygen carrying capacity of RBC resulting in painful crisis, hemolytic anemia, and infection susceptibility. SCD affects around 100,000 individuals in USA alone and 14 million people globally. SCD affected individuals have high mortality rates. Early detection and constant monitoring of this disease is essential. The following review focuses on various methodologies that have emerged in the diagnosis of SCD. Also, low cost methods that can be ...


S100b As A Potential Biomarker For Concussion In Male And Female Collegiate Rugby Athletes, Monica L. Ortiz 2018 Humboldt State University

S100b As A Potential Biomarker For Concussion In Male And Female Collegiate Rugby Athletes, Monica L. Ortiz

Theses and projects

Sport related concussions are among the top ten most common sport injuries. Substantial and mounting evidence points to extensive short and long term negative consequences from mismanaged sport related concussions. Consequently, researchers have called for better diagnostic concussion tests that are rapid, reliable, sensitive, specific and objective. The purpose of this research was to determine the ability of salivary S100B to detect concussions, predict concussion symptom resolution time, and correlate with changes in neurocognitive performance over the course of one athletic season. A repeated measures of salivary S100B and neurocognitive performance using the ImPACT test and a concussion symptom questionnaire ...


Carcinogenesis In Prostate Cancer: The Role Of Long Non-Coding Rnas, John Aird, Anne-Marie Baird, Marvin C.J Lim, Ray McDermott, Stephen P. Finn, Steven G. Gray 2018 Department of Histopathology and Morbid Anatomy, School of Medicine, Trinity College Dublin, Ireland

Carcinogenesis In Prostate Cancer: The Role Of Long Non-Coding Rnas, John Aird, Anne-Marie Baird, Marvin C.J Lim, Ray Mcdermott, Stephen P. Finn, Steven G. Gray

Articles

LncRNAs appear to play a considerable role in tumourigenesis through regulating key processes in cancer cells such as proliferative signalling, replicative immortality, invasion and metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. LncRNAs have been reported to play a role in prostate cancer, particularly in regulating the androgen receptor signalling pathway. In this review article, we summarise the role of 34 lncRNAs in prostate cancer with a particular focus on their role in the androgen receptor signalling pathway and the epithelial to mesenchymal transition pathway.


Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong 2018 Old Dominion University

Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong

Bioelectrics Publications

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in ...


Esope-Equivalent Pulsing Protocols For Calcium Electroporation: An In Vitro Optimization Study On 2 Cancer Cell Models, Stefania Romeo, Anna Sannino, Maria Rosaria Scarfi, P. Thomas Vernier, Ruggero Cadossi, Julie Gehl, Olga Zeni 2018 Old Dominion University

Esope-Equivalent Pulsing Protocols For Calcium Electroporation: An In Vitro Optimization Study On 2 Cancer Cell Models, Stefania Romeo, Anna Sannino, Maria Rosaria Scarfi, P. Thomas Vernier, Ruggero Cadossi, Julie Gehl, Olga Zeni

Bioelectrics Publications

Reversible electroporation is used to increase the uptake of chemotherapeutic drugs in local tumor treatment (electrochemotherapy) by applying the pulsing protocol (8 rectangular pulses, 1000 V/cm, 100 µs) standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy multicenter trial. Currently, new electrochemotherapy strategies are under development to extend its applicability to tumors with different histology. Electrical parameters and drug type are critical factors. A possible approach is to test pulse parameters different from European Standard Operating Procedure on Electrochemotherapy but with comparable electroporation yield (European Standard Operating Procedure on Electrochemotherapy-equivalent protocols). Moreover, the use of non-toxic ...


Outer Limits Of Biotechnologies: A Jewish Perspective, John D. Loike, Alan H. Kadish 2018 Touro College

Outer Limits Of Biotechnologies: A Jewish Perspective, John D. Loike, Alan H. Kadish

Office of the President Publications and Research

A great deal of biomedical research focuses on new biotechnologies such as gene editing, stem cell biology and reproductive medicine, which have created a scientific revolution. While the potential medical benefits of this research may be far-reaching, ethical issues related to non-medical applications of these technologies are demanding. We analyze, from a Jewish legal perspective, some of the ethical conundrums that society faces in pushing the outer limits in researching these new biotechnologies.


Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe 2018 Old Dominion University

Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

Bioelectrics Publications

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the ...


Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar 2018 Old Dominion University

Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar

Bioelectrics Publications

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA ...


Role Of Mycobacterium Avium Paratuberculosis (Map) And Tnfsf15 Snps On Tl1a In Cd, Sayf Al-Deen Hassouneh 2018 University of Central Florida

Role Of Mycobacterium Avium Paratuberculosis (Map) And Tnfsf15 Snps On Tl1a In Cd, Sayf Al-Deen Hassouneh

Electronic Theses and Dissertations

Tumor Necrosis Factor-Like Ligand 1a (TL1A) is a cytokine encoded by Tumor Necrosis Factor Super Family 15 gene (TNFSF15) gene mostly in endothelial cells which binds to T-cells and foments the production of pro-inflammatory cytokines including TNF-α, IL-6, IL-1b, IFN- γ and IL-13. TL1A level is elevated in inflammatory diseases including Crohn's Disease (CD). Although Single Nucleotide Polymorphisms (SNPs) in TNFSF15 have been reported in CD, no studies have investigated the effect of these SNPs on TL1A, inflammation, and susceptibility to Mycobacterium avium subspecies paratuberculosis (MAP) infection. MAP is a strong candidate in CD pathogenesis. This study is designed ...


Development Of A Non-Human Primate Model For Staphylococcus Aureus Nasal Carriage, Amanda Lasseter 2018 University of Central Florida

Development Of A Non-Human Primate Model For Staphylococcus Aureus Nasal Carriage, Amanda Lasseter

Electronic Theses and Dissertations

Staphylococcus aureus nasal carriage (SANC) is largely asymptomatic, but presents a risk of autoinfection and dissemination to new immunocompromised hosts. SA disease states range from mild cutaneous infections to life-threatening bacteremia. Historically utilized rodent models do not naturally carry SA in the nose, are insufficient in longitudinal SANC experimentation, and lack immune factors that are vital in human clearance of SA. The nasal passages of non-human primates are similar anatomically and histologically, and reproductive mucosal studies have shown similar immune responses to pathogens and human-relevant microbial profiles. Seventeen captive pigtailed macaques (Macaca nemestrina) were found to naturally carry SA in ...


Functionalizing Titanium Implants With Bioactive Peptides To Increase Osseointegration, Neil Bernard 2018 The University of Akron

Functionalizing Titanium Implants With Bioactive Peptides To Increase Osseointegration, Neil Bernard

Williams Honors College, Honors Research Projects

Orthopedic surgeries have continued to increase, but the material of choice remains constant: titanium. Titanium has become the benchmark implant material due to its durability and non-immunogenic properties. However, while high rates of success are correlated with joint replacement surgery, certain patients with predisposed diseases such as diabetes or arthritis may have increased complications.1 This can be due to lack of osseointegration due to decreased bone formation and mineralization,2 which will lead to increased rates of infection or aseptic loosening of the implant from the bone. 3 Current methods to alleviate these complications include invasive revisional surgeries, which ...


A Scale Space Local Binary Pattern (Sslbp) – Based Feature Extraction Framework To Detect Bones From Knee Mri Scans, Jinyeong Mun 2018 South Dakota State University

A Scale Space Local Binary Pattern (Sslbp) – Based Feature Extraction Framework To Detect Bones From Knee Mri Scans, Jinyeong Mun

Electronic Theses and Dissertations

The medical industry is currently working on a fully autonomous surgical system, which is considered a novel modality to go beyond technical limitations of conventional surgery. In order to apply an autonomous surgical system to knees, one of the primarily responsible areas for supporting the total weight of human body, accurate segmentation of bones from knee Magnetic Resonance Imaging (MRI) scans plays a crucial role. In this paper, we propose employing the Scale Space Local Binary Pattern (SSLBP) feature extraction, a variant of local binary pattern extractions, for detecting bones from knee images. The proposed methods consist of two phases ...


Achieving Totally Local Anticoagulation On Blood Contacting Devices, Rana Gbyli, Anna Mercaldi, Harihara Sundaram, Kagya Amoako 2017 University of New Haven

Achieving Totally Local Anticoagulation On Blood Contacting Devices, Rana Gbyli, Anna Mercaldi, Harihara Sundaram, Kagya Amoako

Mechanical and Industrial Engineering Faculty Publications

The recent years have witnessed an increased activity in biocompatibility research aimed at limiting biomaterial-induced blood coagulation. From 2008 to 2016, a total of $36,946,764.00 USD was awarded in grants to 213 research proposals and as large as 50.4% ($18,627,854.00) of that award monies were distributed to 101 proposals over the fiscal years of FY14 to FY16 alone. However, the complexity in blood responses to biomaterials, variability in blood function between individuals and animal species, and differences in medical device application and test setting all continue to pose difficulties in making a breakthrough ...


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