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https://www.readbyqxmd.com/read/29132995/comparative-functional-potency-of-dna-vaccines-encoding-plasmodium-falciparum-transmission-blocking-target-antigens-pfs48-45-and-pfs25-administered-alone-or-in-combination-by-in-vivo-electroporation-in-rhesus-macaques
#1
Dibyadyuti Datta, Geetha P Bansal, Brooke Grasperge, Dale S Martin, Mario Philipp, Dietlind Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Antibodies recognizing conformational epitopes in Pfs48/45, an antigen expressed on the surface of Plasmodium falciparum gametes and zygotes, have firmly established Pfs48/45 as a promising transmission blocking vaccine (TBV) candidate. However, it has been difficult to reproducibly express Pfs48/45 in a variety of recombinant expression systems. The goal of our studies was to evaluate functional immunogenicity of Pfs48/45 using DNA vaccine format in rhesus macaques. An additional goal was to ensure that when used in combination with another malarial antigen, specific immunity to both antigens was not compromised...
November 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29132266/in-silico-molecular-docking-and-simulation-studies-on-novel-chalcone-and-flavone-hybrid-derivatives-with-1-2-3-triazole-linkage-as-vital-inhibitors-of-plasmodium-falciparum-dihydroorotate-dehydrogenase
#2
Mahalakshmi Thillainayagam, Kullappan Malathi, Sudha Ramaiah
The structural motifs of chalcones, flavones and triazoles with varied substitutions have been studied for the anti-malarial activity. In this study, 25 novel derivatives of chalcone and flavone hybrid derivatives with 1, 2, 3 - triazole linkage are docked with Plasmodium falciparum dihydroorotate dehydrogenase to establish their inhibitory activity against Plasmodium falciparum. The best binding conformation of the ligands at the catalytic site of dihydroorotate dehydrogenase are selected to characterize the best bound ligand using the best consensus score and the number of hydrogen bond interactions...
November 13, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29114153/genetic-polymorphism-of-plasmodium-vivax-duffy-binding-protein-in-malarious-areas-in-southeastern-of-iran
#3
Mehdi Nateghpour, Afsaneh Motevalli Haghi, Bahare Naderi, Zargham Sepehrizadeh
Plasmodium vivax parasite causes the largest number of malaria infection in some malarious areas of the world including Iran. Considering transfer and genetic dynamics of the parasite population in a specific area can help us to predict the spread of the infection either emergence of new cases or drug resistance in the context of elimination program in the malarious areas. Study on the genetic diversity of common alleles in a given geographical area, for vaccine and immune level studies can be important. The purpose of this study was to know the status of P...
December 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/29107642/linking-epcr-binding-pfemp1-to-brain-swelling-in-pediatric-cerebral-malaria
#4
Anne Kessler, Selasi Dankwa, Maria Bernabeu, Visopo Harawa, Samuel A Danziger, Fergal Duffy, Sam D Kampondeni, Michael J Potchen, Nicholas Dambrauskas, Vladimir Vigdorovich, Brian G Oliver, Sarah E Hochman, Wenzhu B Mowrey, Ian J C MacCormick, Wilson L Mandala, Stephen J Rogerson, D Noah Sather, John D Aitchison, Terrie E Taylor, Karl B Seydel, Joseph D Smith, Kami Kim
Brain swelling is a major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling. We found that parasite var transcripts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite biomass and low platelet levels, are strong indicators of CM cases with malarial retinopathy...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29071567/novel-anti-adipogenic-activity-of-anti-malarial-amodiaquine-through-suppression-of-ppar%C3%AE-activity
#5
Tae Hee Kim, Hyo Kyeong Kim, Eun Sook Hwang
Amodiaquine (AQ) was developed as a selective drug against Plasmodium falciparum malaria infection and has received increasing attention as a therapeutic agent for the treatment of rheumatoid arthritis, Parkinson's disease, and cancer due to its anti-inflammatory, anti-proliferative, and autophagic-lysosomal blockade properties. As autophagy activation is involved in promoting adipogenic differentiation, we examined whether anti-autophagic AQ affected adipocyte differentiation of 3T3-L1 pre-adipocytes. AQ dose-dependently and significantly suppressed adipocyte differentiation in conjunction with decreases in lipid droplet formation and expression of adipogenic markers including adiponectin, adipocyte fatty acid-binding protein 2 (aP2), resistin, and leptin...
October 25, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29061131/proguanil-and-cycloguanil-are-organic-cation-transporter-and-multidrug-and-toxin-extrusion-substrates
#6
Maarten van der Velden, Albert Bilos, Jeroen J M W van den Heuvel, Sanna R Rijpma, Evelien G E Hurkmans, Robert W Sauerwein, Frans G M Russel, Jan B Koenderink
BACKGROUND: Malaria, HIV/AIDS, and tuberculosis endemic areas show considerable geographical overlap, leading to incidence of co-infections. This requires treatment with multiple drugs, potentially causing adverse drug-drug interactions (DDIs). As anti-malarials are generally positively charged at physiological pH, they are likely to interact with human organic cation transporters 1 and 2 (OCT1 and OCT2). These transporters are involved in the uptake of drugs into hepatocytes and proximal tubule cells for subsequent metabolic conversion or elimination...
October 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29045442/a-semi-synthetic-glycosaminoglycan-analogue-inhibits-and-reverses-plasmodium-falciparum-cytoadherence
#7
Mark A Skidmore, Khairul Mohd Fadzli Mustaffa, Lynsay C Cooper, Scott E Guimond, Edwin A Yates, Alister G Craig
A feature of mature Plasmodium falciparum parasitized red blood cells is their ability to bind surface molecules of the microvascular endothelium via the parasite-derived surface protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). This ligand is associated with the cytoadherence pathology observed in severe malaria. As pRBC treated with effective anti-malarial drugs are still able to cytoadhere, there is therefore a need to find an adjunct treatment that can inhibit and reverse the adhesion process...
2017: PloS One
https://www.readbyqxmd.com/read/29025399/plasmodium-falciparum-epcr-binding-pfemp1-expression-increases-with-malaria-disease-severity-and-is-elevated-in-retinopathy-negative-cerebral-malaria
#8
Estela Shabani, Benjamin Hanisch, Robert O Opoka, Thomas Lavstsen, Chandy C John
BACKGROUND: Expression of group A and the A-like subset of group B Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM)...
October 13, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28982133/simultaneous-assessment-of-iodine-iron-vitamin-a-malarial-antigenemia-and-inflammation-status-biomarkers-via-a-multiplex-immunoassay-method-on-a-population-of-pregnant-women-from-niger
#9
Eleanor Brindle, Lorraine Lillis, Rebecca Barney, Sonja Y Hess, K Ryan Wessells, Césaire T Ouédraogo, Sara Stinca, Michael Kalnoky, Roger Peck, Abby Tyler, Christopher Lyman, David S Boyle
Deficiencies of vitamin A, iron, and iodine are major public health concerns in many low- and middle-income countries, but information on their status in populations is often lacking due to high costs and logistical challenges associated with assessing micronutrient status. Accurate, user-friendly, and low-cost analytical tools are needed to allow large-scale population surveys on micronutrient status. We present the expansion of a 7-plex protein microarray tool for the simultaneous measurement of up to seven biomarkers with relevance to the assessment of the key micronutrients iron, iodine, and vitamin A, and inflammation and malaria biomarkers: α-1-acid glycoprotein, C-reactive protein, ferritin, retinol binding protein 4, soluble transferrin receptor, thyroglobulin, and histidine-rich protein II...
2017: PloS One
https://www.readbyqxmd.com/read/28964258/measuring-ex-vivo-drug-susceptibility-in-plasmodium-vivax-isolates-from-cambodia
#10
Suwanna Chaorattanakawee, Chanthap Lon, Soklyda Chann, Kheang Heng Thay, Nareth Kong, Yom You, Siratchana Sundrakes, Chatchadaporn Thamnurak, Sorayut Chattrakarn, Chantida Praditpol, Kritsanai Yingyuen, Mariusz Wojnarski, Rekol Huy, Michele D Spring, Douglas S Walsh, Jaymin C Patel, Jessica Lin, Jonathan J Juliano, Charlotte A Lanteri, David L Saunders
BACKGROUND: While intensive Plasmodium falciparum multidrug resistance surveillance continues in Cambodia, relatively little is known about Plasmodium vivax drug resistance in Cambodia or elsewhere. To investigate P. vivax anti-malarial susceptibility in Cambodia, 76 fresh P. vivax isolates collected from Oddar Meanchey (northern Cambodia) in 2013-2015 were assessed for ex vivo drug susceptibility using the microscopy-based schizont maturation test (SMT) and a Plasmodium pan-species lactate dehydrogenase (pLDH) ELISA...
September 30, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28948179/plasmodium-falciparum-histidine-rich-protein-2-plasma-concentrations-are-higher-in-retinopathy-negative-cerebral-malaria-than-in-severe-malarial-anemia
#11
Gregory S Park, Robert O Opoka, Estela Shabani, Alexis Wypyszynski, Benjamin Hanisch, Chandy C John
BACKGROUND: Malaria retinopathy has been proposed as marker of "true" cerebral malaria (CM), ie, coma due to Plasmodium falciparum vs coma due to other causes, with incidental P falciparum parasitemia. Plasma P falciparum histidine-rich protein-2 (PfHRP2) concentrations distinguish retinopathy-positive (RP) from retinopathy-negative (RN) CM but have not been compared between RN CM and other forms of severe malaria or asymptomatic parasitemia (AP). METHODS: We compared plasma PfHRP2 concentrations in 260 children with CM (247 examined for retinopathy), 228 children with severe malarial anemia (SMA), and 30 community children with AP...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28929019/heterologous-expression-of-plasmodium-vivax-apical-membrane-antigen-1-pvama1-for-binding-peptide-selection
#12
Ching Hoong Chew, Yvonne Ai Lian Lim, Kek Heng Chua
BACKGROUND: Plasmodium is an obligate intracellular parasite. Apical membrane antigen 1 (AMA1) is the most prominent and well characterized malarial surface antigen that is essential for parasite-host cell invasion, i.e., for sporozoite to invade and replicate within hepatocytes in the liver stage and merozoite to penetrate and replicate within erythrocytes in the blood stage. AMA1 has long served as a potent antimalarial drug target and is a pivotal vaccine candidate. A good understanding of the structure and molecular function of this Plasmodium protein, particularly its involvement in host-cell adhesion and invasion, is of great interest and hence it offers an attractive target for the development of novel therapeutics...
2017: PeerJ
https://www.readbyqxmd.com/read/28902417/genetic-variants-related-to-disease-susceptibility-and-immunotolerance-in-the-duffy-antigen-receptor-for-chemokines-darc-fy-gene-in-the-black-lion-tamarin-leontopithecus-chrysopygus-primates
#13
Ashley Ansel, James D Lewis, Don J Melnick, Cristiana Martins, Claudio Valladares-Padua, Beatriz Perez-Sweeney
The DARC (Duffy antigen receptor for chemokines) gene encodes the DARC protein, which serves multiple roles in the immune system, as a binding site for the malarial parasites Plasmodium vivax and Plasmodium knowlesi, a promiscuous chemokine receptor and a blood group antigen. Variation in DARC may play particularly significant roles in innate immunity, immunotolerance and pathogen entry in callitrichines, such as the black lion tamarin (Leontopithecus chrysopygus). We compared amino acid sequences of DARC in the black lion tamarin (BLT) to non-human Haplorhine primates and Homo sapiens...
October 2017: American Journal of Primatology
https://www.readbyqxmd.com/read/28879213/dna-loaded-cationic-liposomes-efficiently-function-as-a-vaccine-against-malarial-proteins
#14
Wesley L Fotoran, Rachele Santangelo, Beatriz N M de Miranda, Darrell J Irvine, Gerhard Wunderlich
The delivery of antigens as DNA vaccines is an efficient alternative to induce immune responses against antigens, which are difficult to produce in recombinant form. However, the delivery of naked DNA is ineffective or relies on sophisticated ballistic devices. Here, we show a combination of liposome application and naked DNA vaccine that successfully overcomes these problems. Upon entrapment of plasmids encoding different antigens in cationic particles, transfection efficiencies similar to commercial kits were achieved in in vitro cell cultures...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28875466/native-mass-spectrometry-ion-mobility-and-collision-induced-unfolding-categorize-malaria-antigen-antibody-binding
#15
Yining Huang, Nichole D Salinas, Edwin Chen, Niraj H Tolia, Michael L Gross
Plasmodium vivax Duffy Binding Protein (PvDBP) is a promising vaccine candidate for P. vivax malaria. Recently, we reported the epitopes on PvDBP region II (PvDBP-II) for three inhibitory monoclonal antibodies (2D10, 2H2, and 2C6). In this communication, we describe the combination of native mass spectrometry and ion mobility (IM) with collision induced unfolding (CIU) to study the conformation and stabilities of three malarial antigen-antibody complexes. These complexes, when collisionally activated, undergo conformational changes that depend on the location of the epitope...
November 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28874661/a-potent-series-targeting-the-malarial-cgmp-dependent-protein-kinase-clears-infection-and-blocks-transmission
#16
David A Baker, Lindsay B Stewart, Jonathan M Large, Paul W Bowyer, Keith H Ansell, María B Jiménez-Díaz, Majida El Bakkouri, Kristian Birchall, Koen J Dechering, Nathalie S Bouloc, Peter J Coombs, David Whalley, Denise J Harding, Ela Smiljanic-Hurley, Mary C Wheldon, Eloise M Walker, Johannes T Dessens, María José Lafuente, Laura M Sanz, Francisco-Javier Gamo, Santiago B Ferrer, Raymond Hui, Teun Bousema, Iñigo Angulo-Barturén, Andy T Merritt, Simon L Croft, Winston E Gutteridge, Catherine A Kettleborough, Simon A Osborne
To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28855657/plasmodium-vivax-ligand-receptor-interaction-pvama-1-domain-i-contains-the-minimal-regions-for-specific-interaction-with-cd71-reticulocytes
#17
Gabriela Arévalo-Pinzón, Maritza Bermúdez, Diana Hernández, Hernando Curtidor, Manuel Alfonso Patarroyo
The malarial parasite's invasion is complex, active and coordinated, involving many low and high affinity interactions with receptors on target cell membrane. Proteomics analysis has described around 40 proteins in P. vivax which could be involved in reticulocyte invasion; few have been studied with the aim of elucidating how many of them establish specific interactions with their respective host cells. Given the importance of knowing which of the parasite's protein regions are functionally important for invasion, minimum regions mediating specific interaction between Plasmodium vivax apical membrane antigen 1 (PvAMA-1) and its host cell were here elucidated...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835253/plasmodium-falciparum-hrp2-elisa-for-analysis-of-dried-blood-spot-samples-in-rural-zambia
#18
Lauren E Gibson, Christine F Markwalter, Danielle W Kimmel, Lwiindi Mudenda, Saidon Mbambara, Philip E Thuma, David W Wright
BACKGROUND: Dried blood spots are commonly used for sample collection in clinical and non-clinical settings. This method is simple, and biomolecules in the samples remain stable for months at room temperature. In the field, blood samples for the study and diagnosis of malaria are often collected on dried blood spot cards, so development of a biomarker extraction and analysis method is needed. METHODS: A simple extraction procedure for the malarial biomarker Plasmodium falciparum histidine-rich protein 2 (HRP2) from dried blood spots was optimized to achieve maximum extraction efficiency...
August 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28790385/connexin-43-enhances-tumor-suppressing-activity-of-artesunate-via-gap-junction-dependent-as-well-as-independent-pathways-in-human-breast-cancer-cells
#19
Asif Raza, Archita Ghoshal, S Chockalingam, Siddhartha Sankar Ghosh
The gap junction (GJ) protein connexin-43 (Cx43) is considered as a tumour suppressor protein for its role in reversing the phenotype of the cancer cells. In this study, we exploited the antitumor property of Cx43 in conjunction with the artesunate (ART), a plant-based active anti-malarial compound. The reactive oxygen species (ROS) generated by ART resulted in DNA damage, which in turn led to DNA damage response by activation of DNA damage repair proteins. GJ deficient MCF-7 cells transfected with Cx43 gene showed an increased sensitivity towards dose-dependent ART treatment and required a significantly lower dose of ART to attain its IC50, as compared to parental cells...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782517/structural-analysis-of-owl-monkey-mhc-dr-shows-that-fully-protective-malaria-vaccine-components-can-be-readily-used-in-humans
#20
Carlos F Suárez, Laura Pabón, Ana Barrera, Jorge Aza-Conde, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
More than 50 years ago the owl monkey (genus Aotus) was found to be highly susceptible to developing human malaria, making it an excellent experimental model for this disease. Microbes and parasites' (especially malaria) tremendous genetic variability became resolved during our malaria vaccine development, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPs are immunologically silent and must be specially modified (mHABPs) to induce a perfect fit into major histocompatibility complex (MHC) molecules (HLA in humans)...
September 30, 2017: Biochemical and Biophysical Research Communications
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