| antimalarial interaction of quinine and quinidine with clarithromycin. | quinine (qn) and quinidine (qnd) have been commonly used as effective and affordable antimalarials for over many years. quinine primarily is used for severe malaria treatment. however, plasmodia resistance to these drugs and poor patient compliance limits their administration to the patients. the declining sensitivity of the parasite to the drugs can thus be dealt with by combining with a suitable partner drug. in the present study qn/qnd was assessed in combination with clarithromycin (cltr), a ... | 2013 | 23137860 |
| in vitro and in vivo antiplasmodial activity of the root extracts of brucea mollis wall. ex kurz. | malaria control is compromised worldwide by continuously evolving drug-resistant strains of the parasite demanding exploration of natural resources for developing newer antimalarials. the northeastern region of india is endemic for malaria characterized by high prevalence of drug-resistant plasmodium falciparum strains. many plants are used by the indigenous communities living in the northeast india in their traditional system of medicine for the treatment of malarial fever. folklore claim of an ... | 2013 | 23108921 |
| high levels of immunoglobulin e autoantibody to 14-3-3 epsilon protein correlate with protection against severe plasmodium falciparum malaria. | plasmodium falciparum infection generally induces elevated total plasma levels of immunoglobulins, some of which recognize self- or parasite-specific antigens. to our knowledge, we are the first to report high levels of functional immunoglobulin e (ige) autoantibodies recognizing brain 14-3-3 protein ε in asymptomatic p. falciparum malaria. 14-3-3 ε protein belongs to a family of proteins that binds to cd81, a member of the tetraspanin superfamily elicited in hepatocyte invasion by sporozoites. ... | 2012 | 22984113 |
| structural architecture and interplay of the nucleotide- and erythrocyte binding domain of the reticulocyte binding protein py235 from plasmodium yoelii. | human malaria is caused by the cyclical invasion of the host's red blood cells (rbcs) by the invasive form of the parasite, the merozoite. the invasion of the rbc involves a range of parasite ligand receptor interactions, a process which is under intensive investigation. two protein families are known to be important in the recognition and invasion of the human erythrocyte, the erythrocyte-binding like (ebl) proteins and the reticulocyte binding like proteins, of which the py235 family in plasmo ... | 2012 | 22878128 |
| remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal plasmodium yoelii malaria. | microarray studies using in vitro cultures of synchronized, blood-stage plasmodium falciparum malaria parasites have revealed a 'just-in-time' cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors. however, direct analysis of transcription in p. falciparum blood-stage parasites obtained from the blood of infected patients suggests that parasite gene expression may be modulated by factors present in the in vivo ... | 2012 | 22866913 |
| in vitro human cell-free expression system for synthesis of malaria proteins. | in this study, we performed cell-free expression of plasmodium proteins using the in vitro human cell-free protein expression systems for dna and mrna. malaria rhoptry genes (pfc14_0344, pfc0120w, py01759, py00763, py07482, and py04666) and a maurer's cleft gene (pfa0680c) identified from proteome analysis studies were cloned into the pt7cfe1-chis expression vector. following a coupled transcription-translation procedure, expressed proteins were analyzed by his-tag staining and by western blotti ... | 2012 | 22782471 |
| novel anti-inflammatory activity of epoxyazadiradione against macrophage migration inhibitory factor: inhibition of tautomerase and proinflammatory activities of macrophage migration inhibitory factor. | macrophage migration inhibitory factor (mif) is responsible for proinflammatory reactions in various infectious and non-infectious diseases. we have investigated the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid purified from neem (azadirachta indica) fruits, against mif. epoxyazadiradione inhibited the tautomerase activity of mif of both human (humif) and malaria parasites (plasmodium falciparum (pfmif) and plasmodium yoelii (pymif)) non-competitively in a reversible ... | 2012 | 22645149 |
| aryl aryl methyl thio arenes prevent multidrug-resistant malaria in mouse by promoting oxidative stress in parasites. | we have synthesized a new series of aryl aryl methyl thio arenes (aamtas) and evaluated antimalarial activity in vitro and in vivo against drug-resistant malaria. these compounds interact with free heme, inhibit hemozoin formation, and prevent plasmodium falciparum growth in vitro in a concentration-dependent manner. these compounds concentration dependently promote oxidative stress in plasmodium falciparum as evident from the generation of intraparasitic oxidants, protein carbonyls, and lipid p ... | 2012 | 22588006 |
| sontochin as a guide to the development of drugs against chloroquine-resistant malaria. | sontochin was the original chloroquine replacement drug, arising from research by hans andersag 2 years after chloroquine (known as "resochin" at the time) had been shelved due to the mistaken perception that it was too toxic for human use. we were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains of plasmodium falciparum in vitro. we prepared derivatives of sontochin, "pharmachins," with alkyl or aryl substituents at ... | 2012 | 22508305 |
| antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores. | a series of novel keto-enamine chalcone-chloroquine based hybrids were synthesized following new methodology developed in our laboratory. the synthesized compounds were screened against chloroquine sensitive strain (3d7) of plasmodium falciparum in an in vitro model. some of the compounds were showing comparable antimalarial activity at par with chloroquine. compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in swiss mice against plasmodium y ... | 2012 | 22464685 |
| plasmodium yoelii blood-stage primes macrophage-mediated innate immune response through modulation of toll-like receptor signalling. | toll-like receptors (tlrs) signalling is reported to be primed by the infection of human malaria parasite, plasmodium falciparum. however, little is known about the regulation of macrophages tlr signalling by the infection of lethal or non-lethal strain of rodent malaria parasites. | 2012 | 22463100 |
| design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies. | the present study describes the synthesis of a series of new 4-aminoquinoline-derived thiazolidines and evaluation of their antimalarial activity against a nf-54 strain of plasmodium falciparum in vitro and n-67 strain of plasmodium yoelii in vivo. among the series, two compounds, 2-(4-chloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-amide hydrochloride (14) and 2-(2,6-dichloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-ami ... | 2013 | 22432870 |
| evidence for the contribution of the hemozoin synthesis pathway of the murine plasmodium yoelii to the resistance to artemisinin-related drugs. | plasmodium falciparum malaria is a major global health problem, causing approximately 780,000 deaths each year. in response to the spreading of p. falciparum drug resistance, who recommended in 2001 to use artemisinin derivatives in combination with a partner drug (called act) as first-line treatment for uncomplicated falciparum malaria, and most malaria-endemic countries have since changed their treatment policies accordingly. currently, act are often the last treatments that can effectively an ... | 2012 | 22403683 |
| the species specificity of immunity generated by live whole organism immunisation with erythrocytic and pre-erythrocytic stages of rodent malaria parasites and implications for vaccine development. | a promising strategy for the development of a malaria vaccine involves the use of attenuated whole parasites, as these present a greater repertoire of antigens to the immune system than subunit vaccines. the complexity of the malaria parasite's life cycle offers multiple stages on which to base an attenuated whole organism vaccine. an important consideration in the design and employment of such vaccines is the diversity of the parasites that are infective to humans. the most valuable vaccine wou ... | 2012 | 22846785 |
| do mixed infections matter? assessing virulence of mixed-clone infections in experimental human and murine malaria. | malaria parasites within an individual infection often consist of multiple strains (clonal populations) of a single species, which have the potential to interact both with one another, and with the host immune system. several effects of these interactions have been measured in different parasite systems including competition and mutualism; however, direct observation of these effects in human malaria has been limited by sampling complexities and inherent ethical limitations. | 2015 | 26334940 |
| induction of multifunctional broadly reactive t cell responses by a plasmodium vivax circumsporozoite protein recombinant chimera. | plasmodium vivax is the most widespread species of plasmodium, causing up to 50% of the malaria cases occurring outside sub-saharan africa. an effective vaccine is essential for successful control and potential eradication. a well-characterized vaccine candidate is the circumsporozoite protein (csp). preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with csp. on the basis of our reported appr ... | 2015 | 26169267 |
| reticulocyte-prone malaria parasites predominantly invade cd71hi immature cells: implications for the development of an in vitro culture for plasmodium vivax. | the lack of a continuous in vitro culture system for blood stages of malarial parasites with a unique tropism for reticulocytes, such as plasmodium vivax and the plasmodium yoelii 17x reticulocyte-prone strain, hinders research in these organisms. the maturation of reticulocytes into erythrocytes is a complex process involving the selective removal of membrane proteins such as the transferrin receptor, cd71. in order to advance in the characterization of infected cells during experimental infect ... | 2013 | 24289105 |
| mir-451 limits cd4(+) t cell proliferative responses to infection in mice. | micrornas (mirnas) are major regulators of cell responses, particularly in stressed cell states and host immune responses. some mirnas have a role in pathogen defense, including regulation of immune responses to plasmodium parasite infection. using a nonlethal mouse model of blood stage malaria infection, we have found that mir-451(-/-) mice infected with plasmodium yoelii xnl cleared infection at a faster rate than did wild-type (wt) mice. mir-451(-/-) mice had an increased leukocyte response t ... | 2017 | 28378118 |
| magnetic nanovectors for the development of dna blood-stage malaria vaccines. | dna vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (spions), polyethylenimine (pei), and hyaluronic acid (ha) to deliver malaria dna encoding plasmodium yoelii (py) merozoite surface protein msp119 (spions/pei/dna + ha gene complex) to dendritic cells and transfect them with high efficiency in vitro. herein, we ... | 2017 | 28336871 |
| dc-derived il-10 modulates pro-inflammatory cytokine production and promotes induction of cd4(+)il-10(+) regulatory t cells during plasmodium yoelii infection. | the cytokine il-10 plays a crucial role during malaria infection by counteracting the pro-inflammatory immune response. we and others demonstrated that plasmodium yoelii infection results in enhanced il-10 production in cd4(+) t cells accompanied by the induction of an immunosuppressive phenotype. however, it is unclear whether this is a direct effect caused by the parasite or an indirect consequence due to t cell activation by il-10-producing antigen-presenting cells. here, we demonstrate that ... | 2017 | 28293237 |
| development of a multi-functional nano-device for safe and effective gene delivery to target organs. | nucleic acids are expected as novel effective medicines, although they require a drug delivery system (dds). complexes of nucleic acids with cationic liposomes and cationic polymers have been mainly used as dds for clinical use. however, most cationic complexes have disadvantages such as strong cytotoxicity and low biocompatibility. we previously found that a plasmid dna (pdna) complex coated with biodegradable γ-polyglutamic acid (γ-pga) provided adequate gene expression without cytotoxicity. b ... | 2016 | 27803485 |
| myeloperoxidase attenuates pathogen clearance during plasmodium yoelii nonlethal infection. | myeloperoxidase (mpo), a leukocyte-derived enzyme mainly secreted by activated neutrophils, is known to be involved in the immune response during bacterial and fungal infection and inflammatory diseases. nevertheless, the role of mpo in a parasitic disease like malaria is unknown. we hypothesized that mpo contributes to parasite clearance. to address this hypothesis, we used plasmodium yoelii nonlethal infection in wild-type and mpo-deficient mice as a murine malaria model. we detected high mpo ... | 2017 | 27795354 |
| cross-regulation of two type i interferon signaling pathways in plasmacytoid dendritic cells controls anti-malaria immunity and host mortality. | type i interferon (ifn) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pdcs) still remain unclear. here, we have shown that nucleic acid sensors cgas-, sting-, mda5-, mavs-, or transcription factor irf3-deficient mice produced high amounts of type i ifn-α and ifn-β (ifn-α/β) in the serum and were resistant to lethal plasmodium yoelii ym infection. robust ifn-α/β production was abolished when gene encoding nucleic acid sensor tlr7, signal ... | 2016 | 27793594 |
| sting-licensed macrophages prime type i ifn production by plasmacytoid dendritic cells in the bone marrow during severe plasmodium yoelii malaria. | malaria remains a global health burden causing significant morbidity, yet the mechanisms underlying disease outcomes and protection are poorly understood. herein, we analyzed the peripheral blood of a unique cohort of malawian children with severe malaria, and performed a comprehensive overview of blood leukocytes and inflammatory mediators present in these patients. we reveal robust immune cell activation, notably of cd14+ inflammatory monocytes, nk cells and plasmacytoid dendritic cells (pdcs) ... | 2016 | 27792766 |
| tlr4 and tlr9 signals stimulate protective immunity against blood-stage plasmodium yoelii infection in mice. | the mechanisms regulating the induction of protective immunity against blood-stage malaria remain unclear. resistant dba/2 mouse develops a higher th1 response compared with a susceptible balb/c strain during plasmodium yoelii (py) infection. it is known that the t helper cell response is initiated and polarized by dendritic cells (dcs) of the innate immune system, during which tlr4 and tlr9 are important receptors for the innate recognition of the malaria parasite and its products. we hypothesi ... | 2016 | 27646627 |
| functional characteristics of the gut microbiome in c57bl/6 mice differentially susceptible to plasmodium yoelii. | c57bl/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. in a previous study, it was observed that when c57bl/6 mice purchased from different vendors were infected with plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. to gain insight into the mechanism of resistance, ... | 2016 | 27729904 |
| increased cd40 expression enhances early sting-mediated type i interferon response and host survival in a rodent malaria model. | both type i interferon (ifn-i) and cd40 play a significant role in various infectious diseases, including malaria and autoimmune disorders. cd40 is mostly known to function in adaptive immunity, but previous observations of elevated cd40 levels early after malaria infection of mice led us to investigate its roles in innate ifn-i responses and disease control. using a plasmodium yoelii nigeriensis n67 and c57bl/6 mouse model, we showed that infected cd40-/- mice had reduced sting and serum ifn-β ... | 2016 | 27716849 |
| probucol dramatically enhances dihydroartemisinin effect in murine malaria. | artemisinin-based combination therapy (act) has been adopted as national policy for the first-line treatment in large number of malaria-endemic regions. however, artemisinin-resistant parasites have emerged and are spreading, with slow-cleaning parasites being reported in patients treated with act. it means that more parasites are exposed to the partner drug alone and the risk of developing resistant parasites against the partner drug is increasing. therefore, the development of a new method to ... | 2016 | 27634686 |
| a recombinant chimeric ad5/3 vector expressing a multistage plasmodium antigen induces protective immunity in mice using heterologous prime-boost immunization regimens. | an ideal malaria vaccine should target several stages of the parasite life cycle and induce antiparasite and antidisease immunity. we have reported a plasmodium yoelii chimeric multistage recombinant protein (p. yoelii linear peptide chimera/recombinant modular chimera), engineered to express several autologous t cell epitopes and sequences derived from the circumsporozoite protein and the merozoite surface protein 1. this chimeric protein elicits protective immunity, mediated by cd4(+) t cells ... | 2016 | 27574299 |
| an atypical splenic b cell progenitor population supports antibody production during plasmodium infection in mice. | hematopoietic stem and progenitor cells (hspcs) function to replenish the immune cell repertoire under steady-state conditions and in response to inflammation due to infection or stress. whereas the bone marrow serves as the primary niche for hematopoiesis, extramedullary mobilization and differentiation of hspcs occur in the spleen during acute plasmodium infection, a critical step in the host immune response. in this study, we identified an atypical hspc population in the spleen of c57bl/6 mic ... | 2016 | 27448588 |
| differential spleen remodeling associated with different levels of parasite virulence controls disease outcome in malaria parasite infections. | infections by malaria parasites can lead to very different clinical outcomes, ranging from mild symptoms to death. differences in the ability of the spleen to deal with the infected red blood cells (irbcs) are linked to differences in virulence. using virulent and avirulent strains of the rodent malaria parasite plasmodium yoelii, we investigated how parasite virulence modulates overall spleen function. following parasite invasion, a difference in parasite virulence was observed in association w ... | 2017 | 27303680 |
| chemically attenuated blood-stage plasmodium yoelii parasites induce long-lived and strain-transcending protection. | the development of a vaccine is essential for the elimination of malaria. however, despite many years of effort, a successful vaccine has not been achieved. most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuated whole-parasite vaccines are now receiving close scrutiny. here, we test chemically attenuated plasmodium yoelii 17x and demonstrate significant protection following homologous and heterologous blood-stage challenge. protection agains ... | 2016 | 27245410 |
| pymif enhances the inflammatory response in a rodent model by stimulating cd11b(+) ly6c(+) cells accumulation in spleen. | macrophage migration inhibitory factor (pmif) expressed by plasmodium parasites has been proved to be similar to the mammalian mif in both structure and biological activity and is a critical upstream regulator in antimalaria innate immunity. in this work, using a genetically modified (mif-ko) strain of highly lethal rodent plasmodium yoelii 17xl (py17xl), we found that pymif could increase the secretion of pro-inflammatory factors by eliciting the cd11b(+) ly6c(+) cells accumulated in the spleen ... | 2016 | 27028001 |
| plasmodium yoelii infection of balb/c mice results in expansion rather than induction of cd4(+) foxp3(+) regulatory t cells. | recently, we demonstrated elevated numbers of cd4(+) foxp3(+) regulatory t (treg) cells in plasmodium yoelii-infected mice contributing to the regulation of anti-malarial immune response. however, it remains unclear whether this increase in treg cells is due to thymus-derived treg cell expansion or induction of treg cells in the periphery. here, we show that the frequency of foxp3(+) treg cells expressing neuropilin-1 (nrp-1) decreased at early time-points during p. yoelii infection, whereas per ... | 2016 | 26932746 |
| repetitive live sporozoites inoculation under arteether chemoprophylaxis confers protection against subsequent sporozoite challenge in rodent malaria model. | inoculation with live sporozoites under prophylactic antimalarial cover (cps-immunization) represents an alternate approach to develop sterile, reproducible, and long-term protection against malaria. here, we have employed arteether (art), a semi synthetic derivative of artemisinin to explore its potential as a chemoprophylaxis candidate in cps approach and systematically compared the protective potential of arteether with mefloquine, azithromycin and primaquine. blood stage patency and quantita ... | 2016 | 26925772 |
| new orally active diphenylmethyl-based ester analogues of dihydroartemisinin: synthesis and antimalarial assessment against multidrug-resistant plasmodium yoelii nigeriensis in mice. | a new series of ester analogues of artemisinin 8a-f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g-j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (mdr) plasmodium yoelii nigeriensis in swiss mice via oral route. these diphenylmethyl-based ester analogues 8a-f were found to be 2-4 folds more active than the antimalarial drugs β-arteether 4 and artesunic acid 5. ester 8a, the most active compound of the series, pro ... | 2016 | 26898813 |
| resistance and susceptibility to malarial infection: a host defense strategy against malaria. | in an effort to understand what limits the virulence of malaria parasites in relation to the host genetic and immunogenic background, we investigated the possibility that the parasite and host genotype crossover interactions constrain virulence. | 2017 | 26811732 |
| utr introns, antisense rna and differentially spliced transcripts between plasmodium yoelii subspecies. | the rodent malaria parasite plasmodium yoelii is an important animal model for studying host-parasite interaction and molecular basis of malaria pathogenesis. although a draft genome of p. yoelii yoelii ym is available, and rna sequencing (rna-seq) data for several rodent malaria species (rmp) were reported recently, variations in coding regions and structure of mrna transcript are likely present between different parasite strains or subspecies. sequencing of cdna libraries from additional paras ... | 2016 | 26791272 |
| depletion of phagocytic cells during nonlethal plasmodium yoelii infection causes severe malaria characterized by acute renal failure in mice. | in the current study, we examined the effects of depletion of phagocytes on the progression of plasmodium yoelii 17xnl infection in mice. strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. t ... | 2016 | 26755155 |
| parasite-specific cd4+ ifn-γ+ il-10+ t cells distribute within both lymphoid and nonlymphoid compartments and are controlled systemically by interleukin-27 and icos during blood-stage malaria infection. | immune-mediated pathology in interleukin-10 (il-10)-deficient mice during blood-stage malaria infection typically manifests in nonlymphoid organs, such as the liver and lung. thus, it is critical to define the cellular sources of il-10 in these sensitive nonlymphoid compartments during infection. moreover, it is important to determine if il-10 production is controlled through conserved or disparate molecular programs in distinct anatomical locations during malaria infection, as this may enable s ... | 2015 | 26459508 |
| measurement of antibody-mediated reduction of plasmodium yoelii liver burden by bioluminescent imaging. | antibodies against the infectious sporozoite stage of malaria have been shown to be effective in preventing infection of the liver and in mitigating the ensuing blood stage. however, only a handful of antibody targets have been vetted and shown to be successful in mediating in vivo protection. even more limited are the means with which to measure how effectively antibodies can reduce the number of parasites establishing infection in the liver. traditionally, only qpcr of infected mouse livers co ... | 2015 | 26450380 |
| inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal salmonella during concurrent malaria parasite infection. | childhood malaria is a risk factor for disseminated infections with non-typhoidal salmonella (nts) in sub-saharan africa. while hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to nts, it is not known whether malaria affects resistance to intestinal colonization with nts. to address this question, we utilized a murine model of co-infection. infection of mice with plasmodium yoelii elicited infiltration of inflammatory macrophages and t cells i ... | 2015 | 26434367 |
| effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection. | the current preventions of malaria are protection against mosquito bites and taking chemoprophylactic anti-malarial drugs. however, drug therapies are usually associated with adverse events and emergency of drug-resistant malaria parasites. previous study showed that host plasma alpha-tocopherol deficiency enhanced resistance against malaria infection in mice. here, we report a new prevention strategy against malaria by using anti-hyperlipidemia drugs, ezetimibe, berberine, cholestyramine, and p ... | 2016 | 26358099 |
| assessment of real-time method to detect liver parasite burden under different experimental conditions in mice infected with plasmodium yoelii sporozoites. | use of highly specific, sensitive and quantitative real-time pcr (qrt-pcr) based methods greatly facilitate the monitoring of experimental drug intervention and vaccination efficacy targeting liver stage malaria parasite. here, in this study we have used qrt-pcr to detect the growing liver stage parasites following inoculation of plasmodium yoelii sporozoite. route of sporozoite administration and size of the sporozoite inoculums are two major determinants that affect the liver stage parasite lo ... | 2015 | 26341953 |
| genome-wide analysis of host-plasmodium yoelii interactions reveals regulators of the type i interferon response. | invading pathogens trigger specific host responses, an understanding of which might identify genes that function in pathogen recognition and elimination. in this study, we performed trans-species expression quantitative trait locus (ts-eqtl) analysis using genotypes of the plasmodium yoelii malaria parasite and phenotypes of mouse gene expression. we significantly linked 1,054 host genes to parasite genetic loci (lod score ≥ 3.0). using lod score patterns, which produced results that differed fr ... | 2015 | 26190101 |
| a transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of the host cells preferred by malaria parasites. | ifn-γ plays both pathological and protective roles during blood-stage malaria. one of its pathological roles is its contribution to anemia by suppressing erythropoiesis. here, to evaluate the effects of ifn-γ-mediated alterations in erythropoiesis on the course of malaria infection, mice deficient in ifn-γ (gko) were infected with two strains of the rodent malaria parasite plasmodium yoelii, 17xl (pyl) and 17xnl (pynl), whose host cell ranges differ. regardless of genotype, all mice infected wit ... | 2015 | 26136736 |
| a plasmodium α/β-hydrolase modulates the development of invasive stages. | the bud emergence (bem)46 proteins are evolutionarily conserved members of the α/β-hydrolase superfamily, which includes enzymes with diverse functions and a wide range of substrates. here, we identified a plasmodium bem46-like protein (pblp) and characterized it throughout the life cycle of the rodent malaria parasite plasmodium yoelii. the plasmodium bem46-like protein is shown to be closely associated with the parasite plasma membrane of asexual erythrocytic stage schizonts and exo-erythrocyt ... | 2015 | 26118838 |
| [the ratio of treg/thl7 cells from mice infected with plasmodium yoelii in the early stage of infection]. | to investigate the change of treg/th17 cell ratio in mice infected with plasmodium yoelii 17xl in the early stage of infection. | 2014 | 25902671 |
| lethal and nonlethal murine malarial infections differentially affect apoptosis, proliferation, and cd8 expression on thymic t cells. | although thymic atrophy and apoptosis of the double-positive (dp) t cells have been reported in murine malaria, comparative studies investigating the effect of lethal and nonlethal plasmodium infections on the thymus are lacking. we assessed the effects of p. yoelii lethal (17xl) and nonlethal (17xnl) infections on thymic t cells. both strains affected the thymus. 17xl infection induced dp t-cell apoptosis and a selective decrease in surface cd8 expression on developing thymocytes. by contrast, ... | 2015 | 25886201 |
| antimalarial activity of tulathromycin in a murine model of malaria. | there is an urgent need for new antimalarial agents and strategies to treat and control malaria. this study shows an antiplasmodium effect of tulathromycin in mice infected with plasmodium yoelii. the administration of tulathromycin around the time of infection prevented the progression of disease in 100% of the animals. in addition, highly parasitized mice treated with tulathromycin showed a decreased parasite burden and cleared the parasite faster than did untreated infected mice. | 2015 | 25870067 |
| cd47 regulates the phagocytic clearance and replication of the plasmodium yoelii malaria parasite. | several plasmodium species exhibit a strong age-based preference for the red blood cells (rbc) they infect, which in turn is a major determinant of disease severity and pathogenesis. the molecular basis underlying this age constraint on the use of rbc and its influence on parasite burden is poorly understood. cd47 is a marker of self on most cells, including rbc, which, in conjunction with signal regulatory protein alpha (expressed on macrophages), prevents the clearance of cells by the immune s ... | 2015 | 25713361 |
| arteether nanoemulsion for enhanced efficacy against plasmodium yoelii nigeriensis malaria: an approach by enhanced bioavailability. | the present work is focused on the preparation of nanoemulsions (nes) loaded with arteether (art) for its enhanced efficacy against malaria parasites. art-nes have been prepared using high pressure homogenization (hph) technique with the aim of improving its solubility and thus its bioavailability. art-nes were optimized in terms of pressure and number of cycles. globule size and size distributions were chosen as quality parameters. the maximum drug loading was achieved up to 93 ± 7.4% with glob ... | 2015 | 25616971 |
| nanoparticles modify dendritic cell homeostasis and induce non-specific effects on immunity to malaria. | many current vaccines to a specific pathogen influence responses to other pathogens in a process called heterologous immunity. we propose that their particulate nature contributes to non-specific effects. herein, we demonstrate polystyrene nanoparticles modulate dendritic cell (dc) homeostasis, thereby promoting a persistent enhanced state of immune readiness to a subsequent infectious challenge. | 2015 | 25573111 |
| early treatment with chloroquine inhibits the immune response against plasmodium yoelii infection in mice. | chloroquine (cq), a well-known anti-malarial drug, has long been used for the treatment of autoimmune diseases because of its profound immunomodulatory effects. however, whether this drug modifies anti-malaria immune response is still not clear. here we studied the immunomodulatory role of cq in a mouse model of malaria. dba/2 mice were infected with plasmodium yoelii (py) parasite (intraperitoneal injection of parasitized erythrocytes) and divided into three groups. two groups received single d ... | 2014 | 25477006 |
| early and late b cell immune responses in lethal and self-cured rodent malaria. | icr mice have heterogeneous susceptibility to lethal plasmodium yoelii yoelii 17xl from the first days of experimental infection as evidenced by the different parasitemia levels and clinical outcomes. this mouse model has revealed specific immune responses on peripheral blood correlating with the infection fate of the animals. to search for immune-markers linked to parasitemia we examined b lymphocytes in organs of the immune system as key effectors of rodent immunity against malaria. to determi ... | 2015 | 25466589 |
| ependymal damage in a plasmodium yoelii yoelii lethal murine malaria model. | malaria continues to be a major global health problem, and over 40% of the world's population is at risk. severe or complicated malaria is defined by clinical or laboratory evidence of vital organ dysfunction, including dysfunction of the central nervous system (cns). the pathogenesis of complicated malaria has not been completely elucidated; however, the development of the multiorgan affection seems to play an important role in the disruption of the blood brain barrier (bbb) that protects the c ... | 2015 | 25252586 |
| t-bet modulates the antibody response and immune protection during murine malaria. | cd4(+) t-cell subtypes govern the synthesis of different ab isotypes and other immune functions. the influence of cd4(+) t-cell differentiation programs on isotype switching and other aspects of host immunological networks during malaria infection are currently poorly understood. here, we used tbx21(-/-) mice deficient for t-bet, a regulator of th1 cd4(+) t-cell differentiation, to examine the effect of th1 cd4(+) t cells on the immune protection to nonlethal murine malaria plasmodium yoelii 17x ... | 2014 | 25047384 |
| efficient editing of malaria parasite genome using the crispr/cas9 system. | malaria parasites are unicellular organisms residing inside the red blood cells, and current methods for editing the parasite genes have been inefficient. the crispr/cas9 (clustered regularly interspaced short palindromic repeats and cas9 endonuclease-mediated genome editing) system is a new powerful technique for genome editing and has been widely employed to study gene function in various organisms. however, whether this technique can be applied to modify the genomes of malaria parasites has n ... | 2014 | 24987097 |
| reactivity of autoantibodies against not only erythrocytes but also hepatocytes in sera of mice with malaria. | in order to further examine the reactivity of autoantibodies, mice were infected with a non-lethal strain of plasmodium yoelii. parasitemia appeared between days 10 and 21. during this period, hyperglycemia and hypothermia were serially obeserved and this phenomenon resembled stress-associated responses. in parallel with parasitemia, autoantibodies appeared against nucleus and double-stranded dna in the sera. to examine further the reactivity of autoantibodies against tissues, immunohistochemica ... | 2014 | 24838093 |
| plasmids encoding protein aggregation domains act as molecular adjuvants for dna vaccines. | dna vaccines provide high tolerability and safety but commonly suffer from suboptimal immunogenicity. we previously reported that a plasmid vector (patrex), encoding the dna sequence for the von willebrand i/a domain of the tumor endothelial marker-8 (tem8) when given in combination with plasmid-encoded tumor antigens acted as a powerful molecular adjuvant enhancing immunity against breast and melanoma tumors. | 2014 | 24828254 |
| association of heme oxygenase 1 with the restoration of liver function after damage in murine malaria by plasmodium yoelii. | the liver efficiently restores function after damage induced during malarial infection once the parasites are cleared from the blood. however, the molecular events leading to the restoration of liver function after malaria are still obscure. to study this, we developed a suitable model wherein mice infected with plasmodium yoelii (45% parasitemia) were treated with the antimalarial α/β-arteether to clear parasites from the blood and, subsequently, restoration of liver function was monitored. liv ... | 2014 | 24818663 |
| dna from pre-erythrocytic stage malaria parasites is detectable by pcr in the faeces and blood of hosts. | following the bite of an infective mosquito, malaria parasites first invade the liver where they develop and replicate for a number of days before being released into the bloodstream where they invade red blood cells and cause disease. the biology of the liver stages of malaria parasites is relatively poorly understood due to the inaccessibility of the parasites to sampling during this phase of their life cycle. here we report the detection in blood and faecal samples of malaria parasite dna thr ... | 2014 | 24704779 |
| in vivo splenic clearance correlates with in vitro deformability of red blood cells from plasmodium yoelii-infected mice. | recent experimental and clinical studies suggest a crucial role of mechanical splenic filtration in the host's defense against malaria parasites. subtle changes in red blood cell (rbc) deformability, caused by infection or drug treatment, could influence the pathophysiological outcome. however, in vitro deformability measurements have not been directly linked in vivo with the splenic clearance of rbcs. in this study, mice infected with malaria-inducing plasmodium yoelii revealed that chloroquine ... | 2014 | 24686065 |
| genome-wide polymorphisms and development of a microarray platform to detect genetic variations in plasmodium yoelii. | the rodent malaria parasite plasmodium yoelii is an important model for studying malaria immunity and pathogenesis. one approach for studying malaria disease phenotypes is genetic mapping, which requires typing a large number of genetic markers from multiple parasite strains and/or progeny from genetic crosses. hundreds of microsatellite (ms) markers have been developed to genotype the p. yoelii genome; however, typing a large number of ms markers can be labor intensive, time consuming, and expe ... | 2016 | 24685548 |
| identification of a new export signal in plasmodium yoelii: identification of a new exportome. | development of the erythrocytic malaria parasite requires targeting of parasite proteins into multiple compartments located within and beyond the parasite confine. beyond the pexel/vts pathway and its characterized players, increasing amount of evidence has highlighted the existence of proteins exported using alternative export-signal(s)/pathway(s); hence, the exportomes currently predicted are incomplete. the nature of these exported proteins which could have a prominent role in most of the pla ... | 2014 | 24636637 |
| mapk phosphotase 5 deficiency contributes to protection against blood-stage plasmodium yoelii 17xl infection in mice. | cell-mediated immunity plays a crucial role in the development of host resistance to asexual blood-stage malaria infection. however, little is known of the regulatory factors involved in this process. in this study, we investigated the impact of mapk phosphotase 5 (mkp5) on protective immunity against a lethal plasmodium yoelii 17xl blood-stage infection using mkp5 knockout c57bl/6 mice. compared with wild-type control mice, mkp5 knockout mice developed significantly lower parasite burdens with ... | 2014 | 24634491 |
| the dichotomy (generation of mabs with functional heterogeneity) in antimalarial immune response in vaccinated/protected mice: a new concept in our understanding of the protective immune mechanisms in malaria. | globally, vaccines have emerged as one of the most effective, safe, and cost-effective public health interventions, and are known to save 2-3 million lives, annually. however, despite various commendable efforts, a suitable human malaria vaccine is yet to see the light of the day. the lack of our complete understanding of the molecular mechanisms of pathogenesis and immune protection in malaria appears to be responsible for this state. earlier, our laboratory has reported that swiss mice vaccina ... | 2014 | 24632591 |
| antimalarial efficacy, cytotoxicity, and genotoxicity of methanolic stem bark extract from hintonia latiflora in a plasmodium yoelii yoelii lethal murine malaria model. | traditional medicines have been used to treat malaria for thousands of years and are the source of artemisinin and quinine derivatives. with the increasing levels of drug resistance, the high cost of artemisisnin-based combination therapies, and fake antimalarials drugs, traditional medicine have become an important and sustainable source of malaria treatment. for the benefit of those who use traditional medicine to treat malaria, there is an urgent need to study the efficacy and toxicity of her ... | 2014 | 24549754 |
| new orally active amino- and hydroxy-functionalized 11-azaartemisinins and their derivatives with high order of antimalarial activity against multidrug-resistant plasmodium yoelii in swiss mice. | by use of artemisinin 1 as the starting material, two new amino- and hydroxy-functionalized 11-azaartemisinins 9 and 11 and their derivatives 12a-g, 13a-g, 14a-g, and 15a-c have been prepared and screened for antimalarial activity by oral route against multidrug-resistant plasmodium yoelii in swiss mice. while azaartemisinins 9 and 11 showed only modest activity, several of their derivatives showed high order of antimalarial activity. biphenyl-based compound 13f, the most active compound of the ... | 2014 | 24524185 |
| strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality. | malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors, and the signaling pathways responsible for these reactions remain unknown or controversial. malaria parasites primarily reside within rbcs, thereby hiding themselves from direct contact and recognition by host immune cells. host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been ... | 2014 | 24474800 |
| differential immune response associated to malaria outcome is detectable in peripheral blood following plasmodium yoelii infection in mice. | malaria infection in humans elicits a wide range of immune responses that can be detected in peripheral blood, but we lack detailed long-term follow-up data on the primary and subsequent infections that lead to naturally acquired immunity. studies on antimalarial immune responses in mice have been based on models yielding homogenous infection profiles. here, we present a mouse model in which a heterogeneous course of plasmodium yoelii lethal malaria infection is produced in a non-congenic icr st ... | 2014 | 24465641 |
| plasmodium genetic loci linked to host cytokine and chemokine responses. | both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. to investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (ccs) and growth rates in mice infected with two plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic ... | 2016 | 24452266 |
| nanoparticle formulation enhanced protective immunity provoked by pygpi8p-transamidase related protein (pytam) dna vaccine in plasmodium yoelii malaria model. | we have previously reported the new formulation of polyethylimine (pei) with gamma polyglutamic acid (γ-pga) nanoparticle (np) to have provided plasmodium yoelii merozoite surface protein-1 (pymsp-1) plasmid dna vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. pygpi8p-transamidase-related protein (pytam) was selected as a possible candidate vaccine antigen by using dna vaccination screening from 29 gpi anchor and signal sequence motif positive gen ... | 2014 | 24440206 |
| the structure of plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design. | merozoite surface protein 1 (msp1) has been identified as a target antigen for protective immune responses against asexual blood stage malaria, but effective vaccines based on msp1 have not been developed so far. we have modified the sequence of plasmodium yoelii msp119 (the c-terminal region of the molecule) and examined the ability of the variant proteins to bind protective monoclonal antibodies and to induce protection by immunization. in parallel, we examined the structure of the protein and ... | 2014 | 24403012 |
| design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced dna vaccine delivery. | dendritic cells (dc) targeting vaccines require high efficiency for uptake, followed by dc activation and maturation. we used magnetic vectors comprising polyethylenimine (pei)-coated superparamagnetic iron oxide nanoparticles, with hyaluronic acid (ha) of different molecular weights (<10 and 900 kda) to reduce cytotoxicity and to facilitate endocytosis of particles into dcs via specific surface receptors. dna encoding plasmodium yoelii merozoite surface protein 1-19 and a plasmid encoding yello ... | 2014 | 24352195 |
| cd8 t cell independent immunity after single dose infection-treatment-vaccination (itv) against plasmodium yoelii. | sporozoite vaccination of both humans and rodents elicits potent anti-malarial immunity, but the dose of sporozoites and the number of immunizations required varies with vaccination approach. here we examine the immunological basis for superior protection afforded from single-dose vaccination with virulent sporozoites administered under prophylatic chloroquine-cover, referred to as infection-treatment-vaccination (itv), compared to the well-studied approach of administering radiation-attenuated ... | 2014 | 24321740 |
| assessment of in vivo antimalarial activities of some selected medicinal plants from turkey. | resistant infections lead to increased necessity of searching novel drugs and drug combinations. the purpose of this paper was to investigate antimalarial properties of some selected medicinal plants that have been traditionally used in turkey for antipyretic and analgesic purposes. lavandula stoecheas subsp. cariensis, phlomis nissolii, phlomis bourgaei, phlomis leucophracta, centaurea hierapolitana, centaurea polyclada, centaurea lydia, scrophularia cryptophila, scrophularia depauperata, scrop ... | 2014 | 24146207 |
| highly sensitive quantitative real-time pcr for the detection of plasmodium liver-stage parasite burden following low-dose sporozoite challenge. | the pre-erythrocytic stages of plasmodium spp. are increasingly recognised as ideal targets for prophylactic vaccines and drug treatments. intense research efforts in the last decade have been focused on in vitro culture and in vivo detection and quantification of liver stage parasites to assess the effects of candidate vaccines or drugs. typically, the onset of blood stage parasitaemia is used as a surrogate endpoint to estimate the efficacy of vaccines and drugs targeting pre-erythrocytic para ... | 2013 | 24098596 |
| apoptosis of non-parasitised red blood cells in plasmodium yoelii malaria. | recently, while studying erythrocytic apoptosis during plasmodium yoelii infection, we observed an increase in the levels of non-parasitised red blood cell (nrbc) apoptosis, which could be related to malarial anaemia. therefore, in the present study, we attempted to investigate whether nrbc apoptosis is associated with the peripheral rbc count, parasite load or immune response. to this end, balb/c mice were infected with p. yoelii 17xl and nrbc apoptosis, number of peripheral rbcs, parasitaemia ... | 2013 | 24037189 |
| the expression of malarial invasion-related molecules is affected by two different nitric oxide-based treatments. | the host immune response to parasitic infections plays an important role in controlling multiplication of the parasite and reducing clinical symptoms and life-threatening complications. nitric oxide (no), an important innate immune factor and classic th1 immune effector, may play a role in inhibiting plasmodium infection. in this study, we used two different approaches (l-arginine [precursor of no] and noc5 [short-time no donor]) to prove the roles of no in malaria infection. we used 6-8 week-ol ... | 2013 | 23951927 |
| observed octameric assembly of a plasmodium yoelii peroxiredoxin can be explained by the replacement of native "ball-and-socket" interacting residues by an affinity tag. | peroxiredoxins (prxs) are ubiquitous and efficient antioxidant enzymes crucial for redox homeostasis in most organisms, and are of special importance for disease-causing parasites that must protect themselves against the oxidative weapons of the human immune system. here, we describe reanalyses of crystal structures of two prxs from malaria parasites. in addition to producing improved structures, we provide normalizing explanations for features that had been noted as unusual in the original repo ... | 2013 | 23934758 |
| carrier protein influences immunodominance of a known epitope: implication in peptide vaccine design. | we investigated how the processing of a given antigen by antigen presenting cells (apc) is dictated by the conformation of the antigen and how this governs the immunodominance hierarchy. to address the question, a known immunodominant sequence of bacteriophage lambda repressor n-terminal sequence 12-26 [λr(12-26)] was engineered at the n and c termini of a heterologous leishmanial protein, kinetoplastid membrane protein-11 (kmp-11); the resulting proteins were defined as n-kmp-11 and c-kmp-11 re ... | 2013 | 23928464 |
| molecular analysis of non-specific protection against murine malaria induced by bcg vaccination. | although the effectiveness of bcg vaccination in preventing adult pulmonary tuberculosis (tb) has been highly variable, epidemiologic studies have suggested that bcg provides other general health benefits to vaccinees including reducing the impact of asthma, leprosy, and possibly malaria. to further evaluate whether bcg immunization protects against malarial parasitemia and to define molecular correlates of this non-specific immunity, mice were vaccinated with bcg and then challenged 2 months la ... | 2013 | 23861742 |
| immunization with apical membrane antigen 1 confers sterile infection-blocking immunity against plasmodium sporozoite challenge in a rodent model. | apical membrane antigen 1 (ama-1) is a leading blood-stage malaria vaccine candidate. consistent with a key role in erythrocytic invasion, ama-1-specific antibodies have been implicated in ama-1-induced protective immunity. ama-1 is also expressed in sporozoites and in mature liver schizonts where it may be a target of protective cell-mediated immunity. here, we demonstrate for the first time that immunization with ama-1 can induce sterile infection-blocking immunity against plasmodium sporozoit ... | 2013 | 23836827 |
| correlation between plasmodium yoelii nigeriensis susceptibility to artemisinin and alkylation of heme by the drug. | evidence of artemisinin (art) resistance in all of the greater mekong region is currently of major concern. understanding of the mechanisms of resistance developed by plasmodium against artemisinin and its derivatives is urgently needed. we here demonstrated that art was able to alkylate heme in mice infected by the art-susceptible strain of plasmodium yoelii nigeriensis, y-control. after long-term drug pressure, the parasite strain (y-art3) was 5-fold less susceptible to art than y-control. in ... | 2013 | 23752508 |
| an essential role for c5ar signaling in the optimal induction of a malaria-specific cd4+ t cell response by a whole-killed blood-stage vaccine. | the protective immunity induced by the whole-killed parasite vaccine against malarial blood-stage infection is dependent on the cd4(+) t cell response. however, the mechanism underlying this robust cd4(+) t cell response elicited by the whole-killed parasite vaccine is still largely unknown. in this study, we observe that immunization with plasmodium yoelii-parasitized rbc lysate activates complement c5 and generates c5a. however, the protective efficacy against p. yoelii 17xl challenge is consi ... | 2013 | 23709683 |
| ability of tep1 in intestinal flora to modulate natural resistance of anopheles dirus. | blocking transmission of malaria is a reliable way to control and eliminate infection. however, in-depth knowledge of the interaction between plasmodium and mosquito is needed. studies suggest that innate immunity is the main mechanism inhibiting development of malaria parasites in the mosquito. recent studies have found that use of antibiotics that inhibit the mosquito gut flora can reduce the immune response of anopheles gambiae, thereby contributing to the development of malaria parasites. in ... | 2013 | 23648664 |
| the role of serine-type serine repeat antigen in plasmodium yoelii blood stage development. | a key step for the survival of the malaria parasite is the release from and subsequent invasion of erythrocytes by the merozoite. differences in the efficiency of these two linked processes have a direct impact on overall parasite burden in the host and thereby virulence. a number of parasite proteases have recently been shown to play important roles during both merozoite egress as well as merozoite invasion. the rodent malaria parasite plasmodium yoelii has been extensively used to investigate ... | 2013 | 23634205 |
| effect of chloroquine, methylene blue and artemether on red cell and hepatic antioxidant defence system in mice infected with plasmodium yoelii nigeriensis. | reactive oxygen species are mediators of tissue injury and are involved in malaria infection. in this study, the status of red cell and hepatic oxidative stress and antioxidant defence indices were investigated during plasmodium yoelii nigeriensis (p. yoelii) infection, and treatment with chloroquine (cq), methylene blue (mb) or artemether (art) in mice. p. yoelii infection caused a significant (p < 0.05) increase in oxidative stress as evidenced by the elevated level of malondialdehyde. this wa ... | 2013 | 23604568 |
| cytokine dysregulation associated with malarial anemia in plasmodium yoelii infected mice. | the mechanisms of malaria anemia remain incompletely understood although much effort has been put on studies in both human and murine systems. hematopoiesis is regulated by the proliferation, differentiation and maturation of erythropoietic progenitor cells into erythrocytes and is tightly controlled by a complex communication network of cytokines as signal mediators. the present study used the murine p. yoelii 17xnl malaria model to investigate the profile of cytokines and leukocytes throughout ... | 2013 | 23573367 |
| a t-cell response to a liver-stage plasmodium antigen is not boosted by repeated sporozoite immunizations. | development of an antimalarial subunit vaccine inducing protective cytotoxic t lymphocyte (ctl)-mediated immunity could pave the way for malaria eradication. experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by plasmodium parasites has so far prohibited the identification of sufficient discrete t-cell antigens to develop subunit vaccines that produce sterile immunity. here, using mice singly immunized with pl ... | 2013 | 23530242 |
| resistance to malaria by enhanced phagocytosis of erythrocytes in lmp7-deficient mice. | general cellular functions of proteasomes occur through protein degradation, whereas the specific function of immunoproteasomes is the optimization of antigen processing associated with mhc class i. we and others previously reported that deficiency in subunits of immunoproteasomes impaired the activation of antigen-specific cd8(+) t cells, resulting in higher susceptibility to tumor and infections. we demonstrated that cd8(+) t cells contributed to protection against malaria parasites. in this s ... | 2013 | 23527234 |
| suppression of host p53 is critical for plasmodium liver-stage infection. | plasmodium parasites infect the liver and replicate inside hepatocytes before they invade erythrocytes and trigger clinical malaria. analysis of host signaling pathways affected by liver-stage infection could provide critical insights into host-pathogen interactions and reveal targets for intervention. using protein lysate microarrays, we found that plasmodium yoelii rodent malaria parasites perturb hepatocyte regulatory pathways involved in cell survival, proliferation, and autophagy. notably, ... | 2013 | 23478020 |
| malaria inhibits surface expression of complement receptor 1 in monocytes/macrophages, causing decreased immune complex internalization. | complement receptor 1 (cr1) expressed on the surface of phagocytic cells binds complement-bound immune complexes (ic), playing an important role in the clearance of circulating ic. this receptor is critical to prevent accumulation of ic, which can contribute to inflammatory pathology. accumulation of circulating ic is frequently observed during malaria, although the factors contributing to this accumulation are not clearly understood. we have observed that the surface expression of cr1 on monocy ... | 2013 | 23440418 |
| synthesis and antimalarial activity of 3,3-spiroanellated 5,6-disubstituted 1,2,4-trioxanes. | novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant plasmodium yoelii nigeriensis in swiss mice by oral route at doses ranging from 96 mg/kg × 4 days to 24 mg/kg × 4 days. the most active compound of the series (compound 25) provided 100% protection at 24 mg/kg × 4 days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising activity. in this model, β-arteether p ... | 2013 | 24900640 |
| biological assay of a novel quinoxalinone with antimalarial efficacy on plasmodium yoelii yoelii. | compound 1-methyl-7-nitro-4-(5-(piperidin-1-yl)pentyl)-3,4-dihydroquinoxalin-2(1h)-one (vam2-6) was evaluated against a blood-induced infection with chloroquine-sensitive plasmodium yoelii yoelii lethal strain in cd1 mice in a 4-day test scheme. ld50 of the compound was 56.51 mg/kg and ld10 was 20.58 mg/kg (taken as the highest dose). animals were treated by oral gavage of 20, 10, and 5 mg/kg. mice in the untreated control group showed a progressively increasing parasitemia leading to mouse deat ... | 2013 | 23338979 |
| accumulation of major histocompatibility complex class ii(+)cd11c(-) non-lymphoid cells in the spleen during infection with plasmodium yoelii is lymphocyte-dependent. | the spleen is the main organ for immune defense during infection with plasmodium parasites and splenomegaly is one of the major symptoms of such infections. using a rodent model of plasmodium yoelii infection, mhc class ii(+)cd11c(-) non-t, non-b cells in the spleen were characterized. although the proportion of conventional dendritic cells was reduced, that of mhc ii(+)cd11c(-) non-t, non-b cells increased during the course of infection. the increase in this subpopulation was dependent on the p ... | 2013 | 23278848 |
| parasites and cancers: parasite antigens as possible targets for cancer immunotherapy. | an adverse relationship between some parasite infections and cancer in the human population has been reported by different research groups. anticancer activity of some parasites such as trypanosoma cruzi, toxoplasma gondii, toxocara canis, acantamoeba castellani and plasmodium yoelii has been shown in experimental animals. moreover, it has been shown that cancer-associated mucin-type o-glycan compositions are made by parasites, therefore cancers and parasites have common antigens. in this report ... | 2012 | 23231515 |
| outcome of primary lethal and nonlethal plasmodium yoelii malaria infection in balb/c and ifn-γ receptor-deficient mice following chloroquine treatment. | ifn-γ receptor-deficient (ifn-γr(-/-)) mice and control wild-type (wt) mice, with or without chloroquine (cq) treatment, were infected intraperitoneally with plasmodium yoelii 17xl (lethal) and p. yoelii 17xnl (nonlethal), and then mouse survival, parasitemia, and antibody production were investigated during the course of infection. without cq treatment, both ifn-γr(-/-) and wt mice were susceptible to infection showing 100 % mortality after infection with 1 × 10(5) p. yoelii 17xl-parasitized er ... | 2013 | 23180129 |
| bile acid-based 1,2,4-trioxanes: synthesis and antimalarial assessment. | a new series of bile acid-based trioxanes 23a-d, 24a-d, 25a-d, 26a, 26b, and 26d have been synthesized and assessed for their antimalarial activity against multidrug-resistant plasmodium yoelii in swiss mice by oral route. the antimalarial activity of these trioxanes showed a strong dependence on the side-chain length; shortening side-chain length lead to increase in activity. the antimalarial activity also showed even stronger dependence on the stereochemistry at c3 and c6 (c21 in figure 5) of ... | 2012 | 23163291 |