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https://www.readbyqxmd.com/read/28929019/heterologous-expression-of-plasmodium-vivax-apical-membrane-antigen-1-pvama1-for-binding-peptide-selection
#1
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
#2
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...
September 13, 2017: American Journal of Primatology
https://www.readbyqxmd.com/read/28879213/dna-loaded-cationic-liposomes-efficiently-function-as-a-vaccine-against-malarial-proteins
#3
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
#4
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...
September 5, 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
#5
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
#6
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
#7
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
#8
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
#9
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)...
August 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28765885/anti-angiogenic-properties-of-artemisinin-derivatives-review
#10
Tianshu Wei, Ju Liu
Angiogenesis, the process involving the development of new blood vessels from existing capillaries, is critical for growth and wound healing. However, pathological angiogenesis contributes to the pathogeneses of numerous diseases, including cancer, rheumatoid arthritis, diabetic retinopathy and macular degeneration. Hence, the inhibition of angiogenesis is an effective therapeutic approach for these diseases. Apart from its anti-malarial properties, artemisinin and its derivatives also exhibit potent anti-angiogenic properties...
July 31, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28765838/sex-specific-molecular-responses-of-quick-to-court-protein-in-indian-malarial-vector-anopheles-culicifacies-conflict-of-mating-versus-blood-feeding-behaviour
#11
Tanwee Das De, Punita Sharma, Charu Rawal, Seena Kumari, Sanjay Tavetiya, Jyoti Yadav, Yasha Hasija, Rajnikant Dixit
Understanding the molecular basis of mosquito behavioural complexity plays a central role in designing novel molecular tools to fight against their vector-borne diseases. Although the olfactory system plays an important role in guiding and managing many behavioural responses including feeding and mating, but the sex-specific regulation of olfactory responses remain poorly investigated. From our ongoing transcriptomic data annotation of olfactory tissue of blood fed adult female An. culicifacies mosquitoes; we have identified a 383 bp long unique transcript encoding a Drosophila homolog of the quick-to-court protein...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28755265/an-in-silico-strategy-for-identification-of-novel-drug-targets-against-plasmodium-falciparum
#12
Subhashree Rout, Namrata Priyadarshini Patra, Rajani Kanta Mahapatra
The apicomplexan parasite Plasmodium falciparum is responsible for global malaria burden. With the reported resistance to artemisinin chemotherapy, there is an urgent need to maintain early phase drug discovery and identify novel drug targets for successful eradication of the pathogen from the host. In our previous work on comparative genomics study for identification of putative essential genes and therapeutic candidates in P. falciparum, we predicted 11 proteins as anti-malarial drug targets from PlasmoDB database...
July 28, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28728558/accuracy-of-a-plasmodium-falciparum-specific-histidine-rich-protein-2-rapid-diagnostic-test-in-the-context-of-the-presence-of-non-malaria-fevers-prior-anti-malarial-use-and-seasonal-malaria-transmission
#13
Francois Kiemde, Massa Dit Achille Bonko, Marc Christian Tahita, Palpouguini Lompo, Toussaint Rouamba, Halidou Tinto, Michael Boele van Hensbroek, Petra F Mens, Henk D F H Schallig
BACKGROUND: It remains challenging to distinguish malaria from other fever causing infections, as a positive rapid diagnostic test does not always signify a true active malaria infection. This study was designed to determine the influence of other causes of fever, prior anti-malarial treatment, and a possible seasonality of the performance of a PfHRP2 RDT for the diagnosis of malaria in children under-5 years of age living in a malaria endemic area. METHODS: A prospective etiology study was conducted in 2015 among febrile children under 5 years of age in Burkina Faso...
July 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28727775/adolescent-health-in-rural-ghana-a-cross-sectional-study-on-the-co-occurrence-of-infectious-diseases-malnutrition-and-cardio-metabolic-risk-factors
#14
Marie Alicke, Justice K Boakye-Appiah, Inusah Abdul-Jalil, Andrea Henze, Markus van der Giet, Matthias B Schulze, Florian J Schweigert, Frank P Mockenhaupt, George Bedu-Addo, Ina Danquah
In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed...
2017: PloS One
https://www.readbyqxmd.com/read/28721818/eurycoma-longifolia-a-potential-phytomedicine-for-the-treatment-of-cancer-evidence-of-p53-mediated-apoptosis-in-cancerous-cells
#15
Hnin Ei Thu, Zahid Hussain, Isa Naina Mohamed, Ahmad Nazrun Shuid
BACKGROUND: Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, anti-malarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent anti-proliferative and anticancer efficacy against various types of human cancers. OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells...
July 18, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28720135/exploring-anti-malarial-potential-of-fda-approved-drugs-an-in-silico-approach
#16
Gayatri Ramakrishnan, Nagasuma Chandra, Narayanaswamy Srinivasan
BACKGROUND: The critically important issue on emergence of drug-resistant malarial parasites is compounded by cross resistance, where resistance to one drug confers resistance to other chemically similar drugs or those that share mode of action. This aspect requires discovery of new anti-malarial compounds or formulation of new combination therapy. The current study attempts to contribute towards accelerating anti-malarial drug development efforts, by exploring the potential of existing FDA-approved drugs to target proteins of Plasmodium falciparum...
July 18, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28719180/heterologous-expression-purification-and-functional-analysis-of-plasmodium-falciparum-phosphatidylinositol-3-kinase
#17
Matthew R Hassett, Anna R Sternberg, Bryce E Riegel, Craig J Thomas, Paul D Roepe
The Plasmodium falciparum malarial parasite genome appears to encode one and only one phosphatidylinositol 3'-kinase (PI3K), and sequence analysis suggests that the enzyme is a "class III"- or "Vps34"-type PI3K. PfVps34 has generated excitement as a possible druggable target and potentially a key target of artemisinin-based antimalarials. In this study, we optimize the PfVps34 gene for heterologous expression in yeast, purify the protein to homogeneity, use a recently validated quantitative assay for phosphatidylinositol 3'-phosphate production from phosphatidylinositol ( Hassett et al...
August 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28712788/antimalarial-agent-artesunate-protects-concanavalin-a-induced-autoimmune-hepatitis-in-mice-by-inhibiting-inflammatory-responses
#18
Xin Zhao, MingJiang Liu, JinGui Li, ShaoJie Yin, YangYang Wu, AnYuan Wang
The anti-malarial drug artesunate (ARS) has been shown to possess anti-inflammatory activity. Its effect on autoimmune hepatitis remains unclear. Concanavalin A (Con A)-induced hepatitis was used in this study to reveal the potential action of ARS and the related mechanism. Mice were pretreated with ARS followed by Con A challenge. Con A caused obvious hepatic injury with higher levels of liver enzymes, elevated pro-inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways...
August 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28699823/the-gmz2-malaria-vaccine-from-concept-to-efficacy-in-humans
#19
Michael Theisen, Bright Adu, Benjamin Mordmüller, Subhash Singh
GMZ2 is a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of Plasmodium falciparum, and is designed with the aim of mimicking naturally acquired anti-malarial immunity. The rationale for combining these two antigens is based on a series of immune epidemiological studies from geographically diverse malaria endemic regions; functional in vitro studies; and pre-clinical studies in rodents and New World monkeys. GMZ2 adjuvanted with alhydrogel® (alum) was well tolerated and immunogenic in three phase 1 studies...
September 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28698001/biolayer-interferometry-predicts-elisa-performance-of-monoclonal-antibody-pairs-for-plasmodium-falciparum-histidine-rich-protein-2
#20
C F Markwalter, I K Jang, R A Burton, G J Domingo, D W Wright
Predicting antibody pair performance in a sandwich format streamlines development of antibody-based diagnostics and laboratory research tools, such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow immunoassays (LFAs). We have evaluated panels of monoclonal antibodies against the malarial parasite biomarker Plasmodium falciparum histidine rich protein 2 (HRP2), including 9 new monoclonal antibodies, using biolayer interferometry (BLI) and screened antibody pairs in a checkerboard ELISA. This study showed BLI predicts antibody pair ELISA performance for HRP2...
October 1, 2017: Analytical Biochemistry
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