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https://www.readbyqxmd.com/read/28930616/development-of-a-semi-automated-image-based-high-throughput-drug-screening-system
#1
Remzi Onur Eren, Dmitry Kopelyanskiy, Dimitri Moreau, Julien Bortoli Chapalay, Marc Chambon, Gerardo Turcatti, Lon-Fye Lye, Stephen M Beverley, Nicolas Fasel
We previously reported that the innate sensing of the endosymbiont Leishmania RNA virus 1 (LRV1) within Leishmania (Viannia) guyanensis through Toll-like receptor 3, worsens the pathogenesis of parasite infection in mice. The presence of LRV1 has been associated with the failure of first-line treatment in patients infected with LRV1 containing -L. guyanensis and -L. braziliensis parasites. Here, we established a semi-automated image-based high-throughput drug screening (HTDS) protocol to measure parasiticidal activity of the Prestwick chemical library in primary murine macrophages infected with LRV1-containing L...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28930585/leishmaniasis-treatment-update-of-possibilities-for-drug-repurposing
#2
Valter Viana Andrade-Neto, Edezio Ferreira Cunha-Junior, Viviane Dos Santos Faioes, Thais Pereira Martins, Raphaela Lopes Silva, Leonor Laura Leon, Eduardo Caio Torres-Santos
The leishmaniases represent a public health problem in under-developed countries and are considered a neglected disease by the World Health Organization (WHO). They are cuased by Leishmania  parasites with different clinical manifestations. Currently, there is no vaccine, and treatment is in-efficient and is associated with both serious side effects often leading to resistance to the parasites. Thus, it is essential to search for new treatment strategies, such as drug repurposing, i.e., the use of drugs that are already used for other diseases...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930253/in-vitro-and-in-vivo-evaluation-of-essential-oil-from-artemisia-absinthium-l-formulated-in-nanocochleates-against-cutaneous-leishmaniasis
#3
Beatriz Tamargo, Lianet Monzote, Abel Piñón, Laura Machín, Marley García, Ramón Scull, William N Setzer
Background: Leishmaniasis is a zoonotic disease caused by protozoan parasites from Leishmania genus. Currently, there are no effective vaccines available and the available therapies are far from ideal. In particular, the development of new therapeutic strategies to reduce the infection caused by Leishmania amazonensis could be considered desirable. Different plant-derived products have demonstrated antileishmanial activity, including the essential oil (EO) from Artemisia absinthium L. (EO-Aa), Asteraceae. Methods: In the present study, the EO-Aa formulated in nanocochleates (EO-Aa-NC) was investigated in vitro against intracellular amastigotes of L...
June 9, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929503/induction-of-heme-oxygenase-1-increases-infection-of-dog-macrophages-by-l-infantum
#4
Breno Fernando Martins de Almeida, Kathlenn Liezbeth Oliveira Silva, Gabriela Lovizutto Venturin, Vanessa Marim Chiku, Aline Aparecida Correa Leal, Anelise Maria Bosco, Paulo Cesar Ciarlini, Valéria Marçal Felix de Lima
AIMS: We aimed to induce and inhibit HO-1, ascertaining its effect on infection rate, parasite load and the levels of superoxide, reactive oxygen species (ROS), nitric oxide (NO), TNF-alpha and IL-10 in cultured macrophages from healthy dogs infected by Leishmania infantum. METHODS AND RESULTS: Macrophages obtained from 15 healthy dogs were cultured alone or infected with L. infantum, with or without association of HO-1 inducer and inhibitor. The infection rate and the parasite load were determined by the number of infected macrophages and number of promastigotes per macrophage, respectively...
September 20, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28929498/dog-skin-parasite-load-tlr-2-il-10-and-tnf-%C3%AE-expression-and-infectiousness
#5
Dandara Camila Morais Pereira-Fonseca, Fernanda Muller de Oliveira-Rovai, Lílian Aparecida Colebrusco Rodas, Carolina Aparecida Carlin Beloti, Rafaela Beatriz Pintor Torrecilha, Píer Kenji Rauschkolb Katsuda Ito, Saulo Vinícius Avanço, Rafael Silva Cipriano, Yuri Tani Utsunomiya, Roberto Mitsuyoshi Hiramoto, Leontides Calvo-Bado, Orin Courtenay, Gisele Fabrino Machado, Valéria Marçal Felix de Lima, Cáris Maroni Nunes
Visceral leishmaniosis is a zoonotic disease that is transmitted by Lutzomyia longipalpis sandflies. Dogs are the main peri-urban reservoir of the disease, and progression of canine leishmaniosis is dependent on the type of immune response elaborated against the parasite. Type 1 immunity is characterized by effective cellular response, with production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α). In contrast, Type 2 immunity is predominantly humoral, associated with progression of the disease, and mediated by anti-inflammatory cytokines such as interleukin 10 (IL-10)...
September 20, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28929123/in-vitro-immunomodulatory-activity-of-a-transition-state-analog-inhibitor-of-human-purine-nucleoside-phosphorylase-in-cutaneous-leishmaniasis
#6
Natália Barbosa Carvalho, Fernanda Ventin de Oliveira Prates, Rafael de Castro da Silva, Mayra Elizabeth Ferreira Dourado, Camila Farias Amorim, Paulo Roberto Lima Machado, Fernanda Grendene Pacheco, Temis Weber Furlanetto Corte, Pablo Machado, Diógenes Santiago Santos, Edgar Marcelino de Carvalho
Cutaneous leishmaniasis (CL) is the most common clinical form of American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis. CL is associated with a strong Th1 immune response. This exacerbated inflammatory response is correlated with severity of disease and delays the healing time of the ulcer. The fourth-generation immucillin derivative (DI4G), a potent inhibitor of purine nucleoside phosphorylase, has been proposed as a promising agent in the treatment of diseases associated with T cell activation...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28928941/computational-design-of-molecular-motors-as-nanocircuits-in-leishmaniasis
#7
Dipali Kosey, Shailza Singh
Cutaneous leishmaniasis is the most common form of lesihmaniasis, caused by Leishmania major and is spread by the bite of a sandfly .This species infects the macrophages and dendritic cells Due to multi-drug resistance, there is a need for a new therapeutic technique. Recently, a novel molecular motor of Leishmania, Myosin XXI, was classified and characterized. In addition, the drug resistance in this organism has been linked with the overexpression of ABC transporters. Systems biology aims to study the simulation and modeling of natural biological systems whereas synthetic biology deals with building novel and artificial biological parts and devices  Together they have contributed enormously to drug discovery, vaccine design and development, infectious disease detection and diagnostics...
2017: F1000Research
https://www.readbyqxmd.com/read/28927848/phagosome-proteomics-to-study-leishmania-s-intracellular-niche-in-macrophages
#8
REVIEW
Geo Semini, Toni Aebischer
Intracellular pathogens invade their host cells and replicate within specialized compartments. In turn, the host cell initiates a defensive response trying to kill the invasive agent. As a consequence, intracellular lifestyle implies morphological and physiological changes in both pathogen and host cell. Leishmania spp. are medically important intracellular protozoan parasites that are internalized by professional phagocytes such as macrophages, and reside within the parasitophorous vacuole inhibiting their microbicidal activity...
September 7, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28927293/antileishmanial-and-antioxidant-potential-of-fractions-and-isolated-compounds-from-nectandra-cuspidata
#9
Lilian Dos Anjos Oliveira Ferreira, Mariana Maciel de Oliveira, Flávia Lais Faleiro, Débora Botura Scariot, Joana Schuelter Boeing, Jesuí Vergílio Visentainer, Mariza Barion Romagnolo, Celso Vataru Nakamura, Maria da Conceição Torrado Truiti
The effects on the viability of promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and citotoxicity in J774.A1 macrophages of ethanolic extract, fractions and isolated compounds that were obtained from the leaves of Nectandra cuspidata were determined. The total phenolics content (TP) and antioxidant activity were assessed using different assays. The ethyl acetate fraction (EAF) had the best antiproliferative activity (amastigote IC50: 4.42 ± 0.60 μg/mL, promastigote IC50: 33.33 ± 0...
September 19, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28924201/discovery-semisynthesis-antiparasitic-and-cytotoxic-evaluation-of-14-membered-resorcylic-acid-lactones-and-their-derivatives
#10
Xue-Qing Zhang, Carmenza Spadafora, Laura M Pineda, Michelle G Ng, Ji-Hong Sun, Wei Wang, Chang-Yun Wang, Yu-Cheng Gu, Chang-Lun Shao
Ten antifouling 14-membered resorcylic acid lactones 1-10 were isolated previously with low or trace natural abundance from the zoanthid-derived Cochliobolus lunatus fungus. Further optimization of fermentation conditions led to the isolation of two major natural compounds 7 and 8 with multi-gram quantities. By one or two steps, we semisynthesized the six trace natural compounds 1-6 and a series of derivatives 11-27 of compounds 7 and 8 with high yields (65-95%). Compounds 11-13 showed strong antiplasmodial activity against Plasmodium falciparum with IC50 values of 1...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28921566/pegylation-of-cationic-liposomes-encapsulating-soluble-leishmania-antigens-sla-reduces-the-adjuvant-efficacy-of-liposomes-in-murine-model
#11
Hadi Naseri, Faezeh Eskandari, Mahmoud Reza Jaafari, Ali Khamesipour, Azam Abbasi, Ali Badiee
Although there have been several attempts to develop a vaccine against leishmaniasis; no vaccine in human has been developed yet. Liposomes consisting of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against L. major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study...
September 16, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28917755/identification-of-trypanosomatids-by-detecting-single-nucleotide-fingerprints-using-dna-analysis-by-dynamic-chemistry-with-maldi-tof
#12
María Angélica Luque-González, Mavys Tabraue-Chávez, Bárbara López-Longarela, Rosario María Sánchez-Martín, Matilde Ortiz-González, Miguel Soriano-Rodríguez, José Antonio García-Salcedo, Salvatore Pernagallo, Juan José Díaz-Mochón
Protozoan parasites of the Trypanosomatidae family can cause devastating diseases in humans and animals, such as Human African Trypanosomiasis or Sleeping Sickness, Chagas disease and Leishmaniasis. Currently, there are molecular assays for detecting parasitic infections and their post-treatment monitoring based on nucleic acid amplification, but there are still certain limitations which limit the development of assays that can detect and discriminate between parasite infections with a single test. Here, we present the development of a novel molecular assay for the rapid identification of Trypanosomatids, integrating DNA analysis by dynamic chemistry in conjunction with Matrix-Assisted Laser Desorption Ionization - Time-of-Flight Mass Spectrometry (MALDI-ToF)...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28916732/il-4-producing-b-cells-regulate-t-helper-cell-dichotomy-in-type-1-and-type-2-controlled-diseases
#13
Ramona Hurdayal, Hlumani H Ndlovu, Mélanie Revaz-Breton, Suraj P Parihar, Justin Komguep Nono, Melissa Govender, Frank Brombacher
Interleukin-4 (IL-4)-induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite Leishmania major, while conferring immunity to the intestinal trematode Schistosoma mansoni Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice (mb1(cre)IL-4Rα(-/lox)) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (µMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to L...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28915996/alternative-strategy-for-visceral-leishmaniosis-control-hisak70-salmonella-choleraesuis-pulsed-dendritic-cells
#14
Gustavo Domínguez-Bernal, Abel Martínez-Rodrigo, Alicia Mas, M Mar Blanco, José A Orden, Ricardo De La Fuente, Javier Carrión
Here, we describe a novel approach that exploits an attenuated mutant of Salmonella enterica serovar Choleraesuis as carrier to deliver a plasmid encoding protein HisAK70. Subsequently, dendritic cells (DCs) were pulsed with this vaccine vector. The aim of this study was to evaluate the effectiveness of the prepared HisAK70-S. Choleraesuis-pulsed DCs (HisAK70-SAL DCs) against visceral leishmaniosis (VL). In our ex vivo model of infection, the prepared formulations could decrease parasite growth by up to 80% by augmenting the production of IL-12p40 and by reducing arginase activity (ARG)...
October 2017: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/28913164/haemoprotozoa-making-biological-sense-of-molecular-phylogenies
#15
REVIEW
Peter O'Donoghue
A range of protistan parasites occur in the blood of vertebrates and are transmitted by haematophagous invertebrate vectors. Some 48 genera are recognized in bood primarily on the basis of parasite morphology and host specificity; including extracellular kinetoplastids (trypanosomatids) and intracellular apicomplexa (haemogregarines, haemococcidia, haemosporidia and piroplasms). Gene sequences are available for a growing number of species and molecular phylogenies often link parasite and host or vector evolution...
December 2017: International Journal for Parasitology. Parasites and Wildlife
https://www.readbyqxmd.com/read/28912944/photodynamic-therapy-with-bengal-rose-and-derivatives-against-leishmania-amazonensis
#16
Taisa Rocha Navasconi, Vanessa Nesi Dos Reis, Camila Fabiano Freitas, Paulo Cesar de Souza Pereira, Wilker Caetano, Noboru Hioka, Maria Valdrinez Campana Lonardoni, Sandra Mara Alessi Aristides, Thaís Gomes Verzignassi Silveira
Introduction: The treatment of cutaneous leishmaniasis (CL) is based primarily on the use of pentavalent antimonials, which may lead to many side effects limiting their use. Photodynamic therapy (PDT) is an alternative for the treatment of CL, and some xanthene dyes have the potential for use in PDT. Methods: The xanthenes rose bengal B (RB) and its derivatives rose bengal methyl ester (RBMET), and butyl ester (RBBUT) were analyzed for leishmanicidal activity against promastigotes and intracellular amastigotes of Leishmania amazonensis...
2017: Journal of Lasers in Medical Sciences
https://www.readbyqxmd.com/read/28911117/structure-based-domain-assignment-in-leishmania-infantum-endog-characterization-of-a-ph-dependent-regulatory-switch-and-a-c-terminal-extension-that-largely-dictates-dna-substrate-preferences
#17
Cristina Oliva, Pedro A Sánchez-Murcia, Eva Rico, Ana Bravo, Margarita Menéndez, Federico Gago, Antonio Jiménez-Ruiz
Mitochondrial endonuclease G from Leishmania infantum (LiEndoG) participates in the degradation of double-stranded DNA (dsDNA) during parasite cell death and is catalytically inactive at a pH of 8.0 or above. The presence, in the primary sequence, of an acidic amino acid-rich insertion exclusive to trypanosomatids and its spatial position in a homology-built model of LiEndoG led us to postulate that this peptide stretch might act as a pH sensor for self-inhibition. We found that a LiEndoG variant lacking residues 145-180 is indeed far more active than its wild-type counterpart at pH values >7...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28910663/strategies-for-overcoming-tropical-disease-by-ruthenium-complexes-with-purine-analog-application-against-leishmania-spp-and-trypanosoma-cruzi
#18
Marzena Fandzloch, José Manuel Méndez Arriaga, Manuel Sánchez-Moreno, Andrzej Wojtczak, Julia Jezierska, Jerzy Sitkowski, Joanna Wiśniewska, Juan Manuel Salas, Iwona Łakomska
Tropical diseases currently constitute a major health problem and thus a challenge in the field of drug discovery. The current treatments show serious disadvantages due to cost, toxicity, long therapy duration and resistance, and the use of metal complexes as chemotherapeutic agents against these ailments appears to be a very attractive alternative. Herein, we describe three newly synthesized ruthenium complexes with a bioactive molecule, the purine analogue 5,6,7-trimethyl-1,2,4-triazolo[1,5-a]pyrimidine (tmtp): cis,fac-[RuCl2(dmso)3(tmtp)] (1), mer-[RuCl3(dmso)(H2O)(tmtp)]·2H2O (2) and fac,cis-[RuCl3(H2O)(tmtp)2] (3)...
September 1, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28904555/acyclic-sesquiterpenes-from-the-fruit-pericarp-of-sapindus-saponaria-induce-ultrastructural-alterations-and-cell-death-in-leishmania-amazonensis
#19
Amanda Louzano Moreira, Débora Botura Scariot, Bruna Luíza Pelegrini, Greisiele Lorena Pessini, Tânia Ueda-Nakamura, Celso Vataru Nakamura, Izabel Cristina Piloto Ferreira
Previous studies reported antiprotozoal activities of Sapindus saponaria L. The aim of this work was the evaluation of antileishmanial activity and mechanism of action of extract and fractions of S. saponaria L. Hydroethanolic extract (EHA) obtained from fruit pericarps was fractionated using solid-phase extraction in a reversed phase, resulting in fractions enriched with saponins (SAP fraction) and acyclic sesquiterpene oligoglycosides (OGSA fraction). The activities of EHA, SAP, and OGSA were evaluated by antiproliferative assays with promastigote and intracellular amastigote forms...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28903998/shape-form-function-and-leishmania-pathogenicity-from-textbook-descriptions-to-biological-understanding
#20
REVIEW
Jack Sunter, Keith Gull
The shape and form of protozoan parasites are inextricably linked to their pathogenicity. The evolutionary pressure associated with establishing and maintaining an infection and transmission to vector or host has shaped parasite morphology. However, there is not a 'one size fits all' morphological solution to these different pressures, and parasites exhibit a range of different morphologies, reflecting the diversity of their complex life cycles. In this review, we will focus on the shape and form of Leishmania spp...
September 2017: Open Biology
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