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Full-Text Articles in Pharmacy and Pharmaceutical Sciences

Transmission Studies And The Composition Of Prokaryotic Communities Associated With Healthy And Diseased Aplysina Cauliformis Sponges Suggest That Aplysina Red Band Syndrome Is A Prokaryotic Polymicrobial Disease, Matteo Monti, Aurora Giorgi, Cole G. Easson, Deborah J. Gochfeld Dec 2021

Transmission Studies And The Composition Of Prokaryotic Communities Associated With Healthy And Diseased Aplysina Cauliformis Sponges Suggest That Aplysina Red Band Syndrome Is A Prokaryotic Polymicrobial Disease, Matteo Monti, Aurora Giorgi, Cole G. Easson, Deborah J. Gochfeld

Faculty and Student Publications

Aplysina cauliformis, the Caribbean purple rope sponge, is commonly affected by Aplysina Red Band Syndrome (ARBS). This transmissible disease manifests as circular lesions with red margins and results in bare spongin fibers. Leptolyngbya spp. appear to be responsible for the characteristic red coloration but transmission studies with a sponge-derived isolate failed to establish disease, leaving the etiology of ARBS unknown. To investigate the cause of ARBS, contact transmission experiments were performed between healthy and diseased sponges separated by filters with varying pore sizes. Transmission occurred when sponges were separated by filters with pore sizes ≥ 2.5 μm, suggesting a prokaryotic …


Mutants Of The White Abcg Transporter In Drosophila Melanogaster Have Deficient Olfactory Learning And Cholesterol Homeostasis, Jennifer L. Myers, Maria Porter, Nicholas Narwold, Krishna Bhat, Brigitte Dauwalder, Gregg Roman Nov 2021

Mutants Of The White Abcg Transporter In Drosophila Melanogaster Have Deficient Olfactory Learning And Cholesterol Homeostasis, Jennifer L. Myers, Maria Porter, Nicholas Narwold, Krishna Bhat, Brigitte Dauwalder, Gregg Roman

Faculty and Student Publications

Drosophila’s white gene encodes an ATP binding cassette G-subfamily (ABCG) half transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is …


Insulin-Like Growth Factor-1 Differentially Modulates Glutamate-Induced Toxicity And Stress In Cells Of The Neurogliovascular Unit, Cellas A. Hayes, Brandon G. Ashmore, Akshaya Vijayasankar, Jessica P. Marshall Nov 2021

Insulin-Like Growth Factor-1 Differentially Modulates Glutamate-Induced Toxicity And Stress In Cells Of The Neurogliovascular Unit, Cellas A. Hayes, Brandon G. Ashmore, Akshaya Vijayasankar, Jessica P. Marshall

Faculty and Student Publications

The age-related reduction in circulating levels of insulin-like growth factor-1 (IGF-1) is associated with increased risk of stroke and neurodegenerative diseases in advanced age. Numerous reports highlight behavioral and physiological deficits in blood-brain barrier function and neurovascular communication when IGF-1 levels are low. Administration of exogenous IGF-1 reduces the extent of tissue damage and sensorimotor deficits in animal models of ischemic stroke, highlighting the critical role of IGF-1 as a regulator of neurovascular health. The beneficial effects of IGF-1 in the nervous system are often attributed to direct actions on neurons; however, glial cells and the cerebrovasculature are also modulated …


Plant Extract Of Limonium Gmelinii Attenuates Oxidative Responses In Neurons, Astrocytes, And Cerebral Endothelial Cells In Vitro And Improves Motor Functions Of Rats After Middle Cerebral Artery Occlusion, Tulendy Nurkenov, Andrey Tsoy, Farkhad Olzhayev, Elvira Abzhanova Nov 2021

Plant Extract Of Limonium Gmelinii Attenuates Oxidative Responses In Neurons, Astrocytes, And Cerebral Endothelial Cells In Vitro And Improves Motor Functions Of Rats After Middle Cerebral Artery Occlusion, Tulendy Nurkenov, Andrey Tsoy, Farkhad Olzhayev, Elvira Abzhanova

Faculty and Student Publications

There are numerous publications demonstrating that plant polyphenols can reduce oxi-dative stress and inflammatory processes in the brain. In the present study we have investigated the neuroprotective effect of plant extract isolated from the roots of L. gmelinii since it contains a rich source of polyphenols and other biologically active compounds. We have applied an oxidative and inflammatory model induced by NMDA, H2O2, and TNF‐α in human primary neurons and astrocytes, and mouse cerebral endothelial cell (CECs) line in vitro. The levels of ROS generation, NADPH oxidase activation, P‐selectin expression, and activity of ERK1/2 were evaluated by quan-titative immunofluorescence analysis, …


Mapping The Impact Of The Covid-19 Pandemic On Pharmacy Graduate Students’ Wellness, Hyllore Imeri, Saumil Jadhav, Marie Barnard, Meagen Rosenthal Nov 2021

Mapping The Impact Of The Covid-19 Pandemic On Pharmacy Graduate Students’ Wellness, Hyllore Imeri, Saumil Jadhav, Marie Barnard, Meagen Rosenthal

Faculty and Student Publications

Background: The COVID-19 pandemic has resulted in significant changes in pharmacy graduate students' (PhGS) lives. While pharmacy graduate programs across the U.S. have reported adjustments due to the pandemic, there is currently no data on the PhGS’ wellness, and the impact on and extent to which offered supports and guidance has met PhGS needs. Objective: This study's objectives were 1) to explore PhGS′ perspectives on their challenges and the impact of these challenges on their wellness, and 2) to identify PhGS′ suggestions for pharmacy graduate programs to improve guidance and support offered during the COVID-19 pandemic. Methods: This study conducted …


Expression Of Mhc Class I Polypeptide-Related Sequence A (Mica) In Colorectal Cancer, Ingrid Espinoza, Sumit Agarwal, Marcelo Sakiyama, Veena Shenoy Oct 2021

Expression Of Mhc Class I Polypeptide-Related Sequence A (Mica) In Colorectal Cancer, Ingrid Espinoza, Sumit Agarwal, Marcelo Sakiyama, Veena Shenoy

Faculty and Student Publications

Background: The major histocompatibility complex class I polypeptide-related sequence A (MICA) is one of the ligands of the natural killer group 2D (NKG2D) activating receptor. MICA stimulates NKG2D, which further triggers activation of natural killer cells and leads to killing of infected target cells. To subvert the biological function of NKG2D, tumor cells utilize an escape strategy by shedding overexpressed MICA. In this study, we determined the levels of MICA in colorectal cancers (CRCs). Additionally, we established correlations between MICA expression and clinical characteristics. Publicly available data and bioinformatics tools were used for validation purposes. Methods: We determined the MICA …


Incident Light And Morphology Determine Coral Productivity Along A Shallow To Mesophotic Depth Gradient, Michael P. Lesser, Marc Slattery, Curtis D. Mobley Oct 2021

Incident Light And Morphology Determine Coral Productivity Along A Shallow To Mesophotic Depth Gradient, Michael P. Lesser, Marc Slattery, Curtis D. Mobley

Faculty and Student Publications

While the effects of irradiance on coral productivity are well known, corals along a shallow to mesophotic depth gradient (10–100 m) experience incident irradiances determined by the optical properties of the water column, coral morphology, and reef topography. Modeling of productivity (i.e., carbon fixation) using empirical data shows that hemispherical colonies photosynthetically fix significantly greater amounts of carbon across all depths, and throughout the day, compared with plating and branching morphologies. In addition, topography (i.e., substrate angle) further influences the rate of productivity of corals but does not change the hierarchy of coral morphologies relative to productivity. The differences in …


Computationally Assisted Lead Optimization Of Novel Potent And Selective Mao-B Inhibitors, Vedanjali Gogineni, Manal A. Nael, Narayan D. Chaurasiya, Khaled M. Elokely Oct 2021

Computationally Assisted Lead Optimization Of Novel Potent And Selective Mao-B Inhibitors, Vedanjali Gogineni, Manal A. Nael, Narayan D. Chaurasiya, Khaled M. Elokely

Faculty and Student Publications

A series of dietary flavonoid acacetin 7-O-methyl ether derivatives were computationally designed aiming to improve the selectivity and potency profiles against monoamine oxidase (MAO) B. The designed compounds were evaluated for their potential to inhibit human MAO-A and-B. Compounds 1c, 2c, 3c, and 4c were the most potent with a Ki of 37 to 68 nM against MAO-B. Compounds 1c–4c displayed more than a thousand-fold selectivity index towards MAO-B compared with MAO-A. Moreover, compounds 1c and 2c showed reversible inhibition of MAO-B. These results provide a basis for further studies on the potential application of these modified flavonoids for the …


Sequentialdynamics Of Stearoyl-Coa Desaturase-1(Scd1)/Ligand Binding And Unbinding Mechanism: A Computational Study, Anna B. Petroff, Rebecca L. Weir, Charles R. Yates, Joseph D. Ng Oct 2021

Sequentialdynamics Of Stearoyl-Coa Desaturase-1(Scd1)/Ligand Binding And Unbinding Mechanism: A Computational Study, Anna B. Petroff, Rebecca L. Weir, Charles R. Yates, Joseph D. Ng

Faculty and Student Publications

Stearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases, including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl- CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as an apoprotein. The modeling of SCD1:fatty acid interactions suggests that: (1) SCD1:CoA moiety interactions open the substrate-binding tunnel, (2) SCD1 stabilizes a substrate conformation …


Preparation And In Vitro/In Vivo Evaluation Of Orally Disintegrating/Modified-Release Praziquantel Tablets, Xuemei Wen, Zhaoyou Deng, Yangfeng Xu, Guoqing Yan Oct 2021

Preparation And In Vitro/In Vivo Evaluation Of Orally Disintegrating/Modified-Release Praziquantel Tablets, Xuemei Wen, Zhaoyou Deng, Yangfeng Xu, Guoqing Yan

Faculty and Student Publications

This study was designed to develop orally disintegrating/sustained-release praziquantel (PZQ) tablets using the hot-melt extrusion (HME) technique and direct compression, and subse-quently evaluate their release in in vitro and in vivo pharmacokinetics. For the extrusion process, hypromellose acetate succinate (HPMCAS)-LG was the carrier of pure PZQ, with a standard screw configuration used at an extrusion temperature of 140◦ C and a screw rotation speed of 100 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FTIR) were performed to characterize the extru-date. Orally disintegrating/sustained-release praziquantel tablets (PZQ ODSRTs) were prepared by direct compression …


Structural And Kinetic Analyses Of Holothurian Sulfated Glycans Suggest Potential Treatment For Sars-Cov-2 Infection, Rohini Dwivedi, Priyanka Samanta, Poonam Sharma, Fuming Zhang Oct 2021

Structural And Kinetic Analyses Of Holothurian Sulfated Glycans Suggest Potential Treatment For Sars-Cov-2 Infection, Rohini Dwivedi, Priyanka Samanta, Poonam Sharma, Fuming Zhang

Faculty and Student Publications

Certain sulfated glycans, including those from marine sources, can show potential effects against SARS-CoV-2. Here, a new fucosylated chondroitin sulfate (FucCS) from the sea cucumber Pentacta pygmaea (PpFucCS) (MW ∼10.60 kDa) was isolated and structurally characterized by NMR. PpFucCS is composed of {→3)-β-GalNAcX-(1→4)-β-GlcA-[(3→1)Y]- (1→}, where X = 4S (80%), 6S (10%) or nonsulfated (10%), Y = α- Fuc2,4S (40%), α-Fuc2,4S-(1→4)-α-Fuc (30%), or α-Fuc4S (30%), and S = SO3-. The anti-SARS-CoV-2 activity of PpFucCS and those of the FucCS and sulfated fucan isolated from Isostichopus badionotus (IbFucCS and IbSF) were compared with that of heparin. IC50 values demonstrated the activity of …


Growth And Feeding In The Sponge Agelas Tubulata From Shallow To Mesophotic Depths On Grand Cayman Island, Keir J. Macartney, Amelia Clayshulte Abraham, Marc Slattery, Michael P. Lesser Sep 2021

Growth And Feeding In The Sponge Agelas Tubulata From Shallow To Mesophotic Depths On Grand Cayman Island, Keir J. Macartney, Amelia Clayshulte Abraham, Marc Slattery, Michael P. Lesser

Faculty and Student Publications

On Caribbean coral reefs, sponges are important members of the benthic community and play multiple roles in ecosystem structure and function. They have an important role in benthic-pelagic coupling, consuming particulate organic matter (POM) and dissolved organic matter (DOM) and in turn providing food in the form of sponge biomass or the release of detritus for a variety of coral reef organisms. Throughout the Caribbean, sponges show consistent increases in their abundance and growth rates as depth increases into the mesophotic zone (30–150 m). This has been hypothesized to be driven by bottom-up forces, particularly the increased supply of nitrogen-rich …


Targeted Downregulation Of Myc Through G-Quadruplex Stabilization By Dnai, Alexandra Maria Psaras, Katarina T. Chang, Taisen Hao, Tracy A. Brooks Sep 2021

Targeted Downregulation Of Myc Through G-Quadruplex Stabilization By Dnai, Alexandra Maria Psaras, Katarina T. Chang, Taisen Hao, Tracy A. Brooks

Faculty and Student Publications

Modulating the expression or function of the enigmatic MYC protein has demonstrated efficacy in an array of cancer types and a marked potential therapeutic index and safety profile. Despite its high therapeutic value, specific and selective inhibitors or downregulating therapeutics have proven difficult to develop. In the current study, we expanded our work on a MYC promoter G-quadruplex (G4) stabilizing DNA clamp to develop an oligonucleotide interfering DNA (DNAi) therapeutic. We explored six DNAi for G4-stabilization through EMSA, DMS footprinting, and thermal stability studies, focusing on the DNAi 5T as the lead therapeutic. 5T, but not its scramble control 5Tscr, …


Tissue-Specific Regulation Of Hnk-1 Biosynthesis By Bisecting Glcnac, Haruka Kawade, Jyoji Morise, Sushil K. Mishra, Shuta Tsujioka Sep 2021

Tissue-Specific Regulation Of Hnk-1 Biosynthesis By Bisecting Glcnac, Haruka Kawade, Jyoji Morise, Sushil K. Mishra, Shuta Tsujioka

Faculty and Student Publications

Human natural killer—1 (HNK-1) is a sulfated glyco-epitope regulating cell adhesion and synaptic functions. HNK-1 and its non-sulfated forms, which are specifically expressed in the brain and the kidney, respectively, are distinctly biosynthesized by two homologous glycosyltransferases: GlcAT-P in the brain and GlcAT-S in the kidney. However, it is largely unclear how the activity of these isozymes is regulated in vivo. We recently found that bisecting GlcNAc, a branching sugar in N-glycan, suppresses both GlcAT-P activity and HNK-1 expression in the brain. Here, we observed that the expression of non-sulfated HNK-1 in the kidney is unexpectedly unaltered in mutant mice …


Adapting Decarbonylation Chemistry For The Development Of Prodrugs Capable Ofin Vivodelivery Of Carbon Monoxide Utilizing Sweeteners As Carrier Molecules, Ladie Kimberly De La Cruz, Xiaoxiao Yang, Anna Menshikh, Maya Brewer Aug 2021

Adapting Decarbonylation Chemistry For The Development Of Prodrugs Capable Ofin Vivodelivery Of Carbon Monoxide Utilizing Sweeteners As Carrier Molecules, Ladie Kimberly De La Cruz, Xiaoxiao Yang, Anna Menshikh, Maya Brewer

Faculty and Student Publications

Carbon monoxide as an endogenous signaling molecule exhibits pharmacological efficacy in various animal models of organ injury. To address the difficulty in using CO gas as a therapeutic agent for widespread applications, we are interested in developing CO prodrugs through bioreversible caging of CO in an organic compound. Specifically, we have explored the decarboxylation-decarbonylation chemistry of 1,2-dicarbonyl compounds. Examination and optimization of factors favorable for maximal CO release under physiological conditions led to organic CO prodrugs using non-calorific sweeteners as leaving groups attached to the 1,2-dicarbonyl core. Attaching a leaving group with appropriate properties promotes the desired hydrolysis-decarboxylation-decarbonylation sequence of …


The Degree Of Polymerization And Sulfation Patterns In Heparan Sulfate Are Critical Determinants Of Cytomegalovirus Entry Into Host Cells, Dipanwita Mitra, Mohammad H. Hasan, John T. Bates, Michael A. Bierdeman Aug 2021

The Degree Of Polymerization And Sulfation Patterns In Heparan Sulfate Are Critical Determinants Of Cytomegalovirus Entry Into Host Cells, Dipanwita Mitra, Mohammad H. Hasan, John T. Bates, Michael A. Bierdeman

Faculty and Student Publications

Several enveloped viruses, including herpesviruses attach to host cells by initially interacting with cell surface heparan sulfate (HS) proteoglycans followed by specific coreceptor engagement which culminates in virus-host membrane fusion and virus entry. Interfering with HS-herpesvirus interactions has long been known to result in significant reduction in virus infectivity indicating that HS play important roles in initiating virus entry. In this study, we provide a series of evidence to prove that specific sulfations as well as the degree of polymerization (dp) of HS govern human cytomegalovirus (CMV) binding and infection. First, purified CMV extracellular virions preferentially bind to sulfated longer …


(E)-2,6,10-Trimethyldodec-8-En-2-Ol: An Undescribed Sesquiterpenoid From Copaiba Oil, Mohammed F. Hawwal, Zulfiqar Ali, Mei Wang, Jianping Zhao Aug 2021

(E)-2,6,10-Trimethyldodec-8-En-2-Ol: An Undescribed Sesquiterpenoid From Copaiba Oil, Mohammed F. Hawwal, Zulfiqar Ali, Mei Wang, Jianping Zhao

Faculty and Student Publications

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography …


Red Algal Sulfated Galactan Binds And Protects Neural Cells From Hiv-1 Gp120 And Tat, Vitor H. Pomin, Fakhri Mahdi, Weihua Jin, Fuming Zhang Aug 2021

Red Algal Sulfated Galactan Binds And Protects Neural Cells From Hiv-1 Gp120 And Tat, Vitor H. Pomin, Fakhri Mahdi, Weihua Jin, Fuming Zhang

Faculty and Student Publications

The potential neuroprotective capacity of four different sulfated glycans: Botryocladia occidentalis-derived sulfated galactan (BoSG) (MW > 100 kDa), Lytechinus variegatus-derived sulfated fucan (LvSF) (MW~90 kDa), high-molecular weight dextran sulfate (DxS) (MW 100 kDa), and unfractionated heparin (UFH) (MW~15 kDa), was assessed in response to the HIV-1 proteins, R5-tropic glycoprotein 120 (gp120) and/or trans-activator of transcription (Tat), using primary murine neurons co-cultured with mixed glia. Compared to control-treated cells in which HIV-1 proteins alone or combined were neurotoxic, BoSG was, among the four tested sulfated glycans, the only one capable of showing significant concentration-dependent neuroprotection against Tat and/or gp120, alone or combined. …


Critical Interactions Between Opioid And Cannabinoid Receptors During Tolerance And Physical Dependence Development To Opioids In The Murine Gastrointestinal Tract: Proof Of Concept, Agata Szymaszkiewicz, Mikołaj Świerczyński, Marcin Talar, Prabhakar Reddy Polepally Aug 2021

Critical Interactions Between Opioid And Cannabinoid Receptors During Tolerance And Physical Dependence Development To Opioids In The Murine Gastrointestinal Tract: Proof Of Concept, Agata Szymaszkiewicz, Mikołaj Świerczyński, Marcin Talar, Prabhakar Reddy Polepally

Faculty and Student Publications

Introduction: Tolerance (TOL) and physical dependence (PD) constitute important limitations of opioid therapy. The aim of our study was to validate research tools to investigate TOL and PD and to characterize the interactions between opioid (OR) and cannabinoid (CB) receptors in these processes in the GI tract. Methods: TOL was assessed through the comparison of morphine ability to inhibit electrically evoked smooth muscles contractility in the mouse ileum that was previously incubated with/without morphine for 1 h. To evaluate the PD, the ileum was incubated with morphine for 10 min, then challenged with naloxone to induce withdrawal response (WR). The …


Phase-Specific And Lifetime Costs Of Multiple Myeloma Among Older Adults In The Us, Kaustuv Bhattacharya, John P. Bentley, Sujith Ramachandran, Yunhee Chang Jul 2021

Phase-Specific And Lifetime Costs Of Multiple Myeloma Among Older Adults In The Us, Kaustuv Bhattacharya, John P. Bentley, Sujith Ramachandran, Yunhee Chang

Faculty and Student Publications

Importance: Health care costs associated with diagnosis and care among older adults with multiple myeloma (MM) are substantial, with cost of care and the factors involved differing across various phases of the disease care continuum, yet little is known about cost of care attributable to MM from a Medicare perspective. Objective: To estimate incremental phase-specific and lifetime costs and cost drivers among older adults with MM enrolled in fee-for-service Medicare. Design, Setting, and Participants: A retrospective cohort study was conducted using population-based registry data from the 2007-2015 Surveillance, Epidemiology, and End Results database linked with 2006-2016 Medicare administrative claims data. …


Identification Of Human Kinin-Forming Enzyme Inhibitors From Medicinal Herbs, Hassan Madkhali, Amer Tarawneh, Zulfiqar Ali, Hoang V. Le Jul 2021

Identification Of Human Kinin-Forming Enzyme Inhibitors From Medicinal Herbs, Hassan Madkhali, Amer Tarawneh, Zulfiqar Ali, Hoang V. Le

Faculty and Student Publications

The goal of this study was to assess the pharmacological effects of black tea (Camellia sinensis var. assamica) water extract on human kinin-forming enzymes in vitro. Tea is a highly consumed beverage in the world. Factor XII (FXII, Hageman factor)-independent-and-dependent activation of prekallikrein to kallikrein leads to the liberation of bradykinin (BK) from high-molecular-weight kininogen (HK). The excessive BK production causes vascular endothelial and nonvascular smooth muscle cell permeability, leading to angioedema. The prevalence of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema appears to be through BK. Both histamine and BK are potent inflammatory mediators. However, the treatments for histamine-mediated angioedema are …


Structure–Activity Relationships Of The Antimalarial Agent Artemisinin 10. Synthesis And Antimalarial Activity Of Enantiomers Of Rac-5Β-Hydroxy-D-Secoartemisinin And Analogs: Implications Regarding The Mechanism Of Action, Mohamed Jahan, Francisco Leon, Frank R. Fronczek, Khaled M. Elokely Jul 2021

Structure–Activity Relationships Of The Antimalarial Agent Artemisinin 10. Synthesis And Antimalarial Activity Of Enantiomers Of Rac-5Β-Hydroxy-D-Secoartemisinin And Analogs: Implications Regarding The Mechanism Of Action, Mohamed Jahan, Francisco Leon, Frank R. Fronczek, Khaled M. Elokely

Faculty and Student Publications

An efficient synthesis of rac-6-desmethyl-5β–hydroxy-D-secoartemisinin 2, a tricyclic analog of R-(+)-artemisinin 1, was accomplished and the racemate was resolved into the (+)-2b and (−)-2a enantiomers via their Mosher Ester diastereomers. Antimalarial activity resided with only the artemisinin-like enantiomer R-(−)-2a. Several new compounds 9–16, 19a, 19b, 22 and 29 were synthesized from rac-2 but the C-5 secondary hydroxyl group was surprisingly unreactive. For example, the formation of carbamates and Mitsunobu reactions were unsuccessful. In order to assess the unusual reactivity of 2, a single crystal X-ray crystallographic analysis revealed a close intramolecular hydrogen bond from the C-5 alcohol to the oxepane …


Assessment Of Evolutionary Relationships For Prioritization Of Myxobacteria For Natural Product Discovery, Andrew Ahearne, Hanan Albataineh, Scot E. Dowd, D. Cole Stevens Jul 2021

Assessment Of Evolutionary Relationships For Prioritization Of Myxobacteria For Natural Product Discovery, Andrew Ahearne, Hanan Albataineh, Scot E. Dowd, D. Cole Stevens

Faculty and Student Publications

Discoveries of novel myxobacteria have started to unveil the potentially vast phylogenetic diversity within the family Myxococcaceae and have brought about an updated approach to myxobacterial classification. While traditional approaches focused on morphology, 16S gene sequences, and biochemistry, modern methods including comparative genomics have provided a more thorough assessment of myxobacterial taxonomy. Herein, we utilize long-read genome sequencing for two myxobacteria previously classified as Archangium primigenium and Chondrococcus macrosporus, as well as four environmental myxobacteria newly isolated for this study. Average nucleotide identity and digital DNA–DNA hybridization scores from comparative genomics suggest previously classified as A. primigenium to instead be …


Rural Community Pharmacies’ Preparedness For And Responses To Covid-19, Delesha M. Carpenter, Tessa Hastings, Salisa Westrick, Meagen Rosenthal Jul 2021

Rural Community Pharmacies’ Preparedness For And Responses To Covid-19, Delesha M. Carpenter, Tessa Hastings, Salisa Westrick, Meagen Rosenthal

Faculty and Student Publications

Background: Few studies have documented rural community pharmacy disaster preparedness. Objectives: To: (1) describe rural community pharmacies’ preparedness for and responses to COVID-19 and (2) examine whether responses vary by level of pharmacy rurality. Methods: A convenience sample of rural community pharmacists completed an online survey (62% response rate) that assessed: (a) demographic characteristics; (b) COVID-19 information source use; (c) interest in COVID-19 testing; (d) infection control procedures; (e) disaster preparedness training, and (f) medication supply impacts. Descriptive statistics were calculated and differences by pharmacy rurality were explored. Results: Pharmacists used the CDC (87%), state health departments (77%), and state …


Transcriptomic Changes And The Roles Of Cannabinoid Receptors And Pparγin Developmental Toxicities Following Exposure To Δ9-Tetrahydrocannabinol And Cannabidiol, Zacharias Pandelides, Neelakanteswar Aluru, Cammi Thornton, Haley E. Watts Jul 2021

Transcriptomic Changes And The Roles Of Cannabinoid Receptors And Pparγin Developmental Toxicities Following Exposure To Δ9-Tetrahydrocannabinol And Cannabidiol, Zacharias Pandelides, Neelakanteswar Aluru, Cammi Thornton, Haley E. Watts

Faculty and Student Publications

Human consumption of cannabinoid-containing products during early life or pregnancy is rising. However, information about the molecular mechanisms involved in early life stage Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) toxicities is critically lacking. Here, larval zebrafish (Danio rerio) were used to measure THC- and CBD-mediated changes on transcriptome and the roles of cannabinoid receptors (Cnr) 1 and 2 and peroxisome proliferator activator receptor γ(PPARγ) in developmental toxicities. Transcriptomic profiling of 96-h postfertilization (hpf) cnr+/+ embryos exposed (6 - 96 hpf) to 4 μM THC or 0.5 μM CBD showed differential expression of 904 and 1095 genes for THC and CBD, respectively, …


Rage Differentially Altered In Vitro Responses In Vascular Smooth Muscle Cells And Adventitial Fibroblasts In Diabetes-Induced Vascular Calcification, Amber M. Kennon, James A. Stewart Jun 2021

Rage Differentially Altered In Vitro Responses In Vascular Smooth Muscle Cells And Adventitial Fibroblasts In Diabetes-Induced Vascular Calcification, Amber M. Kennon, James A. Stewart

Faculty and Student Publications

The Advanced Glycation End-Products (AGE)/Receptor for AGEs (RAGE) signaling pathway exacerbates diabetes-mediated vascular calcification (VC) in vascular smooth muscle cells (VSMCs). Other cell types are involved in VC, such as adventitial fibroblasts (AFBs). We hope to elucidate some of the mechanisms responsible for differential signaling in diabetes-mediated VC with this work. This work utilizes RAGE knockout animals and in vitro calcification to measure calcification and protein responses. Our calcification data revealed that VSMCs calcification was AGE/RAGE dependent, yet AFBs calcification was not an AGE-mediated RAGE response. Protein expression data showed VSMCs lost their phenotype marker, α-smooth muscle actin, and had …


Ethiopian Medicinal Plants Traditionally Used For The Treatment Of Cancer; Part 3: Selective Cytotoxic Activity Of 22 Plants Against Human Cancer Cell Lines, Solomon Tesfaye, Hannah Braun, Kaleab Asres, Ephrem Engidawork Jun 2021

Ethiopian Medicinal Plants Traditionally Used For The Treatment Of Cancer; Part 3: Selective Cytotoxic Activity Of 22 Plants Against Human Cancer Cell Lines, Solomon Tesfaye, Hannah Braun, Kaleab Asres, Ephrem Engidawork

Faculty and Student Publications

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro‐ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF‐7), lung (A427), bladder (RT‐4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC‐103H), pancreatic cancer (DAN‐G), ovarian cancer (A2780), and squamous cell carcinoma of …


Rap1a Regulates Cardiac Fibroblast Contraction Of 3d Diabetic Collagen Matrices By Increased Activation Of The Age/Rage Cascade, Stephanie D. Burr, James A. Stewart Jun 2021

Rap1a Regulates Cardiac Fibroblast Contraction Of 3d Diabetic Collagen Matrices By Increased Activation Of The Age/Rage Cascade, Stephanie D. Burr, James A. Stewart

Faculty and Student Publications

Cardiovascular disease is a common diabetic complication that can arise when cardiac fibroblasts transition into myofibroblasts. Myofibroblast transition can be induced by advanced glycated end products (AGEs) present in the extracellular matrix (ECM) activating RAGE (receptor for advanced glycated end products) to elicit intracellular signaling. The levels of AGEs are higher under diabetic conditions due to the hyperglycemic conditions present in diabetics. AGE/RAGE signaling has been shown to alter protein expression and ROS production in cardiac fibroblasts, resulting in changes in cellular function, such as migration and contraction. Recently, a small GTPase, Rap1a, has been identified to overlap the AGE/RAGE …


Risk Factors For Development Of Initial Clostridioides Difficile Infection, Jamie L. Wagner, Kayla R. Stover, Allison M. Bell, Katie E. Barber Jun 2021

Risk Factors For Development Of Initial Clostridioides Difficile Infection, Jamie L. Wagner, Kayla R. Stover, Allison M. Bell, Katie E. Barber

Faculty and Student Publications

Objectives: The purpose of this study was to identify risk factors for initial complicated Clostridioides difficile infection (CDI). Methods: This retrospective cross-sectional study included adult patients with initial episodes of CDI who received ≥72 h of CDI-active antimicrobials. Patients were categorised into one of two groups: complicated CDI or uncomplicated CDI. A total of 513 patients were screened for inclusion, with complicated CDI patients exhibiting abnormal abdominal CT findings or experiencing death within 30 days post-CDI diagnosis. Results: A total of 203 patients met the inclusion criteria, comprising 143 (70.4%) with uncomplicated CDI and 60 (29.6%) with complicated CDI. Complicated …


Evidence That Maackia Amurensis Seed Lectin (Masl) Exerts Pleiotropic Actions On Oral Squamous Cells With Potential To Inhibit Sars-Cov-2 Infection And Covid-19 Disease Progression, Stephanie A. Sheehan, Kelly L. Hamilton, Edward P. Retzbach, Premalatha Balachandran Jun 2021

Evidence That Maackia Amurensis Seed Lectin (Masl) Exerts Pleiotropic Actions On Oral Squamous Cells With Potential To Inhibit Sars-Cov-2 Infection And Covid-19 Disease Progression, Stephanie A. Sheehan, Kelly L. Hamilton, Edward P. Retzbach, Premalatha Balachandran

Faculty and Student Publications

COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 27 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface “spike” protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia …