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Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke 2017 Atlanta University Center

Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The expression of C-X-C Chemokine Receptor 4 (CXCR4) has been correlated with increased metastatic potential of cancer cells. CXCR4 increases tumor malignancy by encouraging tumors cells to migrate to distal organs expressing its cognate ligand, CXCL12, facilitating metastasis. Thus, targeting the CXCR4/CXCL12 signaling axis provides a good strategy to inhibit the metastatic spread of tumor cells and slow cancer progression. Various studies suggest that cannabis may have anti-proliferative as well as anti-metastatic properties, though a biochemical mechanism describing how this occurs has yet to be discovered. Our lab has confirmed that agonist-bound CXCR4 and agonist-bound Cannabinoid Receptor 2 (CB2 ...


Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana 2017 Seton Hall University

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 ...


B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips 2017 Seton Hall University

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory ...


A Chemoenzymatic Approach For Synthesizing Polymeric Hemoglobin, Johann P. Sigurjonsson 2017 Western Washington University

A Chemoenzymatic Approach For Synthesizing Polymeric Hemoglobin, Johann P. Sigurjonsson

Graduate Student Conference

Polymerized hemoglobin (Hb) molecules have been shown to decrease previously observed adverse events associated with the administration of cell-free hemoglobin. To create these polymers, a method will be developed which employs the site specific ligation reaction of the sortase A enzyme from S. aureus. An Hb mutant (“αcpβ“) previously developed in our lab has been further modified by adding either the sortase recognition sequence, LPXTG, to the C-terminus of the α-subunit (s-αcpβ), or a tetraglycine motif, GGGG, to the N-terminus (n-αcpβ). Three types of sortase mediated ligation (SML) will be employed in this study. First, we will attempt to ligate ...


Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori 2017 University of Rhode Island

Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori

Senior Honors Projects

The genomes of living organisms are under constant bombardment from various sources, including chemical modification stemming from processes within the organisms themselves or from exogenous agents, and from radiation. These sources of genomic damage may induce structural changes in the genome’s most basic functional units, the nucleotides that comprise DNA. Damage to an organism’s DNA may result in the production of dysfunctional or nonfunctional proteins. Failure to repair such damage may result in the compounding of successive mutations within the organism’s genome, the pathogenesis of cancer and various genetic disorders in humans. To ensure their viability, organisms ...


Connecting Energy Metabolism And Neurodegeneration: Pyruvate Kinase And Oxidative Stress, Julia P. Zuercher 2017 College of William and Mary

Connecting Energy Metabolism And Neurodegeneration: Pyruvate Kinase And Oxidative Stress, Julia P. Zuercher

Undergraduate Honors Theses

Pyruvate kinase (PK), an important glycolytic enzyme that catalyzes the final step of glycolysis through an irreversible mechanism to produce energy for the cell, contains nine cysteines, some of which are highly reactive and critical for function. This research sought to develop a protocol to measure quantitatively the functionality of PK under different experimental conditions. Using a three stage, consistent procedure, it was possible to analyze the effects of thiol modification by Ellman’s Reagent (DTNB) and oxidation by hypochlorous acid (HOCl) on PK activity. Results showed that both DTNB and HOCl inhibited activity at high concentrations, which illustrates that ...


Structural Studies On Hiv-1 Protease To Investigate Correlation Between Conformational Dynamics And Drug-Resistance, Rowan Brothers 2017 Georgia State University

Structural Studies On Hiv-1 Protease To Investigate Correlation Between Conformational Dynamics And Drug-Resistance, Rowan Brothers

Georgia State Undergraduate Research Conference

No abstract provided.


Gene 33/Mig6 Regulates Apoptosis And The Dna Damage Response Through Independent Mechanisms, Cen Li, Soyoung Park, Leonard M. Eisenberg, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu 2017 New York Medical College

Gene 33/Mig6 Regulates Apoptosis And The Dna Damage Response Through Independent Mechanisms, Cen Li, Soyoung Park, Leonard M. Eisenberg, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu

NYMC Faculty Posters

Gene 33 (Mig6, ERRFI1) is an inducible adaptor/scaffold protein whose expression can be induced by both stress and mitogenic signals. It contains multiple domains for protein-protein interaction and is involved in a broad spectrum of cellular functions. Gene 33 promotes apoptosis in a cell type-dependent manner. A recent study has linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)]. Here we show that Gene 33 induces apoptosis via both c-Abl/p73 and EGFR/AKT-dependent pathways in lung epithelial and lung carcinoma cells. Ectopic expression of Gene 33 also triggers DDR in an ATM-dependent ...


Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan 2017 Harry S. Truman Memorial Veterans' Hospital

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling ...


Are Gene Polymorphisms Of Fibroblast Growth Factor 10 Associated With Patent Ductus Arteriosus And Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants?, Shaili Amatya, Asma Amin, Umesh Paudel, Lance A. Parton 2017 New York Medical College

Are Gene Polymorphisms Of Fibroblast Growth Factor 10 Associated With Patent Ductus Arteriosus And Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants?, Shaili Amatya, Asma Amin, Umesh Paudel, Lance A. Parton

NYMC Faculty Posters

No abstract provided.


Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch 2017 University of Nebraska at Omaha

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: 2RD0 ...


Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal 2017 George Washington University

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Integrative Systems Biology Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic ...


Anakinra Reduces Blood Pressure And Renal Fibrosis In One Kidney/Doca/Salt-Induced Hypertension, Yeong Hann Ling, Shalini M. Krishnan, Christopher T. Chan, Henry Diep, Dorota Ferens, Jaye Chin-Dusting, Barbara K. Kemp-Harper, Chrishan S. Samuel, Timothy D. Hewitson, Eicke Latz, Ashley Mansell, Christopher G. Sobey, Grant R. Drummond 2017 Monash University

Anakinra Reduces Blood Pressure And Renal Fibrosis In One Kidney/Doca/Salt-Induced Hypertension, Yeong Hann Ling, Shalini M. Krishnan, Christopher T. Chan, Henry Diep, Dorota Ferens, Jaye Chin-Dusting, Barbara K. Kemp-Harper, Chrishan S. Samuel, Timothy D. Hewitson, Eicke Latz, Ashley Mansell, Christopher G. Sobey, Grant R. Drummond

Open Access Articles

OBJECTIVE: To determine whether a clinically-utilised IL-1 receptor antagonist, anakinra, reduces renal inflammation, structural damage and blood pressure (BP) in mice with established hypertension. METHODS: Hypertension was induced in male mice by uninephrectomy, deoxycorticosterone acetate (2.4mg/d,s.c.) and replacement of drinking water with saline (1K/DOCA/salt). Control mice received uninephrectomy, a placebo pellet and normal drinking water. 10days post-surgery, mice commenced treatment with anakinra (75mg/kg/d, i.p.) or vehicle (0.9% saline, i.p.) for 11 days. Systolic BP was measured by tail cuff while qPCR, immunohistochemistry and flow cytometry were used to measure ...


Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker 2017 Chapman University

Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks ...


Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho 2017 New York Medical College

Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho

NYMC Faculty Publications

Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models. Here, we examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9) AD ...


Molecular Modeling Of Novel Tryptamine Analogs With Antibiotic Potential Through Their Inhibition Of Tryptophan Synthase, Jared Schattenkerk 2017 Claremont McKenna College

Molecular Modeling Of Novel Tryptamine Analogs With Antibiotic Potential Through Their Inhibition Of Tryptophan Synthase, Jared Schattenkerk

CMC Senior Theses

The growing prevalence of antibiotic-resistant bacteria is a global health crisis that threatens the effectiveness of antibiotics in medical treatment. Increases in the number of antibiotic-resistant bacteria and a drop in the pharmaceutical development of novel antibiotics have combined to form a situation that is rapidly increasing the likelihood of a post-antibiotic era. The development of antibiotics with novel enzymatic targets is critical to stall this growing crisis. In silico methods of molecular modeling and drug design were utilized in the development of novel tryptamine analogs as potential antibiotics through their inhibition of the bacterial enzyme tryptophan synthase. Following the ...


Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David MacTavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas 2017 University of Alberta

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered intracerebroventricularly ...


Proteomic Approach For Extracting Cytoplasmic Proteins From Streptococcus Sanguinis Using Mass Spectrometry, Fadi Elrami, Kristina Nelson, Ping Xu 2017 Virginia Commonwealth University

Proteomic Approach For Extracting Cytoplasmic Proteins From Streptococcus Sanguinis Using Mass Spectrometry, Fadi Elrami, Kristina Nelson, Ping Xu

Philips Institute for Oral Health Research Publications

Streptococcus sanguinis is a commensal and early colonizer of oral cavity as well as an opportunistic pathogen of infectious endocarditis. Extracting the soluble proteome of this bacterium provides deep insights about the physiological dynamic changes under different growth and stress conditions, thus defining “proteomic signatures” as targets for therapeutic intervention. In this protocol, we describe an experimentally verified approach to extract maximal cytoplasmic proteins from Streptococcus sanguinis SK36 strain. A combination of procedures was adopted that broke the thick cell wall barrier and minimized denaturation of the intracellular proteome, using optimized buffers and a sonication step. Extracted proteome was quantitated ...


Amphetamine-Like Compounds In Pre-Workout Supplements, Andy Hsien Wei Koh 2017 Bond University

Amphetamine-Like Compounds In Pre-Workout Supplements, Andy Hsien Wei Koh

Theses

Pre-workout supplements (PWS), like most nutritional supplements, are classified by the Therapeutic Goods Administration (TGA) in Australia as complementary medicines and are therefore subject to much less stringent regulation compared to pharmaceuticals. Complementary medicines (also known as 'traditional' or 'alternative' medicines) include vitamin, mineral, herbal, aromatherapy and homoeopathic products. The overall goal of this thesis was to determine the amounts of stimulants in PWS, both the biogenic amines derived from Citrus aurantium (CA) extracts as well as caffeine and its dimethylxanthine (DMX) derivatives. Research questions have been put forward relating to the components within PWS and whether they comply with ...


The Autocrine Role Of Proteoglycan-4 (Prg4) In Modulating Osteoarthritic Synoviocyte Proliferation And Expression Of Matrix Degrading Enzymes, Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D. Jay, Khaled A. Elsaid 2017 MCPHS University

The Autocrine Role Of Proteoglycan-4 (Prg4) In Modulating Osteoarthritic Synoviocyte Proliferation And Expression Of Matrix Degrading Enzymes, Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D. Jay, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)- stimulated conditions.

Methods: Cytosolic and nuclear levels of nuclear factor kappa B (NFκB) p50 and p65 subunits in Prg4+/+ and Prg4-/- synoviocytes were studied using western blot. Nuclear translocation ...


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