Publications

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erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia.malaria, a major global health challenge worldwide, is accompanied by a severe anemia secondary to hemolysis and increased erythrophagocytosis. iron is an essential functional component of erythrocyte hemoglobin and its availability is controlled by the liver-derived hormone hepcidin. we examined the regulation of hepcidin during malarial infection in mice using the rodent parasite plasmodium berghei k173. mice infected with plasmodium berghei k173 develop a severe anemia and die after 18 to 22 ...201727658439
maldi-tof ms as an innovative tool for detection of plasmodium parasites in anopheles mosquitoes.malaria is still a major public health issue worldwide, and one of the best approaches to fight the disease remains vector control. the current methods for mosquito identification include morphological methods that are generally time-consuming and require expertise, and molecular methods that require laboratory facilities with relatively expensive running costs. matrix-assisted laser desorption ionization time-of-flight mass spectrometry (maldi-tof ms) technology, routinely used for bacterial id ...201728049524
functional characterization of plasmodium berghei psop25 during ookinete development and as a malaria transmission-blocking vaccine candidate.plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (tbv) candidates. putative secreted ookinete protein 25 (psop25) is a highly conserved ookinete surface protein, and has been shown to be a promising novel tbv target. here, we further investigated the tbv activities of the full-length recombinant psop25 (rpsop25) protein in plasmodium berghei, and characterized the potential functions of psop25 during the p. berghei lif ...201728057055
magnetic nanoparticles are highly toxic to chloroquine-resistant plasmodium falciparum, dengue virus (den-2), and their mosquito vectors.a main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. we investigated the toxicity of magnetic nanoparticles (mnp) produced by magnetospirillum gryphiswaldense (strain msr-1) on chloroquine-resistant (cq-r) and sensitive (cq-s) plasmodium falciparum, dengue virus (den-2), and two of their main vectors, anopheles stephensi and aedes aegypti, respectively. mnp were studied by fourier-transform infrared spectroscopy and transmission elect ...201727815736
anopheles stephensi heme peroxidase hpx15 suppresses midgut immunity to support plasmodium development.the heme peroxidase hpx15 is an evolutionary conserved anopheline lineage-specific gene. previously, we found that this gene is present in the genome of 19 worldwide distributed different species of anopheles mosquito and its orthologs are absent in other mosquitoes, insects, or human. in addition, 65-99% amino acid identity among these 19 orthologs permitted us to hypothesize that the functional aspects of this gene might be also conserved in different anophelines. in this study, we found that ...201728352267
plant hormone cytokinins control cell cycle progression and plastid replication in apicomplexan parasites.cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. here, we show that the apicomplexan parasites toxoplasma gondii and plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. cytokinins regulate the growth and cell cycle progression of t. gondii by mediating expression of the cyclin gene tgcyc4. ...201728344153
extended protection capabilities of an immature dendritic-cell targeting malaria sporozoite vaccine.mouse studies evaluating candidate malaria vaccines have typically examined protective efficacy over the relatively short time frames of several weeks after the final of multiple immunizations. the current study examines the protective ability in a mouse model system of a novel protein vaccine construct in which the adjuvant polyinosinic polycytidilic acid (poly(i:c)) is used in combination with a vaccine in which the immature dendritic cell targeting chemokine, macrophage inflammatory protein 3 ...201728342669
the maternally inheritable wolbachia walbb induces refractoriness to plasmodium berghei in anopheles stephensi.the endosymbiont wolbachia walbb induces refractoriness to plasmodium falciparum in anopheles stephensi, the primary mosquito vector of human malaria in the middle east and south asia. however, it remains unknown whether such refractoriness can be extended to other malaria species. in particular, it was reported that under very specific conditions, walbb can enhance plasmodium infection in some hosts. here, we measured the impact of walbb on the rodent malaria parasite plasmodium berghei in a. s ...201728337184
oxidative stress and genes regulation of cerebral malaria upon zizyphus spina-christi treatment in a murine model.the development and spread of multidrug-resistant strains of malarial parasites have led to an overwhelming increase in the resistance to current antimalarial drugs. the urgent need for alternative antimalarial drugs has directed some of the current studies toward folkloric medicine approaches. interestingly, the zizyphus spina cristi leaf extract (zle) has been found to exhibit antiplasmodial activity. this study evaluated the protective effect of zle against plasmodium berghei-induced cerebral ...201728336326
effects of artesunate on some biochemical parameters in pregnant albino wistar rats challenged with lethal strain plasmodium berghei nk65: appreciating the activities of artemisinin drugs on key pregnancy hormone balance.in humans, malaria in pregnancy can cause serious maternal and foetal morbidity and in extreme untreated cases, foetal mortality occurs. the therapeutic approach to curbing this malaise is the administration of an effective and/or combinations of anti-malaria medicaments. acute or chronic administration of some of these drugs, however, gives rise to some adverse medical conditions including reproductive dysfunction, especially in pregnancy. studies aimed at the hormonal interplays following admi ...201728336173
antimalarial and antiplasmodial activity of husk extract and fractions of zea mays.zea mays l. (poacae) husk decoctions are traditionally used in the treatment of malaria by various tribes in nigeria.201728320254
docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives.a series of 4-anilinoquinoline triazine derivatives were designed, synthesized and screened for in vivo antimalarial activity against a chloroquine-sensitive strain of plasmodium berghei. the compounds were further subjected to in vitro antimalarial activity against chloroquine-resistant w2 strain of plasmodium falciparum and β-haematin inhibition studies. all the compounds exhibited in vivo antimalarial activity better than that shown by the standard drug, chloroquine. twelve out of fifteen com ...201728318947
immunophenotyping of blood mononuclear cells from p. berghei (nk-65) infected and immunized balb/c mice.the present study demonstrates the alterations in the frequencies of helper, cytotoxic and suppressor t cells in blood of p. berghei infected and tpa immunized rodent host towards the induction of protective immune response. statistically significant (p < 0.005) number of cd4(+) t cells was recorded on d9 [post challenge (pc)] meanwhile cd4(+) treg cells were found to be declined in immunized mice as compared to infected. this increase in frequencies of t helper cells points towards the stimulat ...201728316421
comparative susceptibility of different mouse strains to liver-stage infection with plasmodium berghei sporozoites assessed using in vivo imaging.the liver stages of plasmodium parasites are important targets for the discovery and development of prophylactic drugs.201728291500
rhesus macaque and mouse models for down-selecting circumsporozoite protein based malaria vaccines differ significantly in immunogenicity and functional outcomes.non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. transgenic rodent parasites expressing genes of human plasmodium are now routinely used for efficacy studies of human malaria vaccines. mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are suffi ...201728288639
transdermal delivery of oleanolic acid attenuates pro-inflammatory cytokine release and ameliorates anaemia in p. berghei malaria.malaria remains a major health problem in many tropical areas. severe malaria infection is associated with secondary complications including anaemia leading to a need for the search of affordable antimalarial agents that can clear the parasitaemia and ameliorate anaemia during infection. the current study investigated the effects of transdermally delivered oa on malaria parasites, hct and selected plasma cytokine concentrations in p. berghei-infected male sprague-dawley rats. the study was carri ...201728283442
quantitative characterization of hemozoin in plasmodium berghei and vivax.the incidence and global distribution of chloroquine resistant (cr) plasmodium vivax infection has increased since emerging in 1989. the mechanism of resistance in cr p. vivax has not been defined. the resistance likely relates to the formation and disposition of hemozoin as chloroquine's primary mechanism of action involves disruption of hemozoin formation. cr p. berghei strains, like cr p. vivax strains, are confined to reticulocyte host cells and reportedly they do not accumulate appreciable ...201728279945
new derivatives of quinoline-4-carboxylic acid with antiplasmodial activity.new analogues of the recently published compound ddd107498 were prepared. their activities were examined in vitro against the chloroquine-sensitive nf54 strain. the most active were also tested against the multiresistant k1 strain of plasmodium falciparum. a couple of the newly synthesized compounds showed promising antiplasmodial activity and selectivity. a single compound showed adequate reduction of parasitaemia (98.1%) in mice infected with plasmodium berghei. survival time was doubled compa ...201728279559
primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms.primaquine is an anti-malarial used to prevent plasmodium vivax relapses and malaria transmission. however, pq metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (g6pd). fifteen pq-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes.201728279180
targeting angiotensin ii type-1 receptor (at1r) inhibits the harmful phenotype of plasmodium-specific cd8(+) t cells during blood-stage malaria.cd8(+) t-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. our group and other have been shown that angiotensin ii (ang ii) and its receptor at1 (at1r), a key effector axis of renin-angiotensin system (ras), have immune regulatory effects on t cells. previously, we showed that inhibition of at1r signaling protects mice against the lethal disease induced by plasmodium berghei anka infection however, most of the ang ii/at1r actions were characterized by using on ...201728261571
vaccination with altered peptide ligands of a plasmodium berghei circumsporozoite protein cd8 t-cell epitope: a model to generate t cells resistant to immune interference by polymorphic epitopes.many pathogens, including the malaria parasite plasmodium falciparum, display high levels of polymorphism within t-cell epitope regions of proteins associated with protective immunity. the t-cell epitope variants are often non-cross-reactive. herein, we show in a murine model, which modifies a protective cd8 t-cell epitope from the circumsporozoite protein (cs) of plasmodium berghei (syipsaeki), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive ...201728261200
in vivo efficacy of top five surveyed ghanaian herbal anti-malarial products.anti-malarial herbal preparations (hps) continue to enjoy high patronage in ghana despite reports that the artemisinin-based combination therapy (act), the recommended first choice for treatment of uncomplicated malaria in the country, remains efficacious. a major issue with the use of these preparations is inadequate or unreliable data on their efficacy and quality. an assessment of the potency and quality of the most popular commercial anti-malarial hps in ghana was, therefore, carried out. th ...201728259160
antimalarials with benzothiophene moieties as aminoquinoline partners.malaria is a severe and life-threatening disease caused by plasmodium parasites that are spread to humans through bites of infected anopheles mosquitoes. here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting plasmodium falciparum parasite growth. synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. benzothiophenes presented in this paper showed improved activities against a chloroquine su ...201728245583
gancidin w, a potential low-toxicity antimalarial agent isolated from an endophytic streptomyces suk10.endophytic streptomyces strains are potential sources for novel bioactive molecules. in this study, the diketopiperazine gancidin w (gw) was isolated from the endophytic actinobacterial genus streptomyces, suk10, obtained from the bark of shorea ovalis tree, and it was tested in vivo against plasmodium berghei pzz1/100. gw exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg(-1) body weight on day four using the 4-day suppression test method on male icr strain mice. comparing gw at ...201728223778
palmitoylation of plasmodium alveolins promotes cytoskeletal function.s-palmitoylation is a post-translational lipid modification that is widespread among plasmodium proteins and essential for parasite development. little is known about the contribution of palmitoylation to the function of individual parasite molecules and structures. alveolins are major components of the subpellicular network (spn), a cortical cytoskeleton primarily involved in providing mechanical strength to the cell. we show here that the alveolin imc1c is palmitoylated on a conserved cysteine ...201728223095
anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria.the widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. in this study, chloroquine derivatives were evaluated for the improved anti-malarial activity.201728212631
erratum to: characterization of a plasmodium berghei sexual stage antigen pbph as a new candidate for malaria transmission-blocking vaccine. 201728209188
cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. the identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. here we demonstrate that members of an apicomplexan-specific protein family-the novel putative transporters (npts)-play key roles in the uptake of cationic amino acids. we show that an npt from toxoplasma gondii (tgnpt1) is a selective arginine tran ...201728205520
the deubiquitinating enzyme cylindromatosis dampens cd8(+) t cell responses and is a critical factor for experimental cerebral malaria and blood-brain barrier damage.cerebral malaria is a severe complication of human malaria and may lead to death of plasmodium falciparum-infected individuals. cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. although cd8(+) t cells have been implicated in the development of murine experimental cerebral malaria (ecm), several other studies have shown that cd8(+) t cells confer protection agai ...201728203236
plasmodium berghei plasmepsin viii is essential for sporozoite gliding motility.plasmodium aspartic proteases, termed plasmepsins (pms) play many critical roles such as haemoglobin degradation, cleavage of pexel proteins and sporozoite development in the parasite life cycle. most of the plasmepsins are well characterized, however the role of pm viii in plasmodium remains unknown. here, we elucidate the functions of pm viii (pbanka_132910) in the rodent malaria parasite plasmodium berghei (pb). by targeted gene deletion, we show that pbpm viii is critical for sporozoite egre ...201728192122
antimalarial, antiplasmodial and analgesic activities of root extract of alchornea laxiflora.alchornea laxiflora (benth.) pax. & hoffman (euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in nigeria.201728183236
the antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria.according to the who, and despite reduction in mortality rates, there were an estimated 438 000 malaria deaths in 2015. therefore new antimalarials capable of limiting organ damage are still required. we show that systemic and lung adenovirus (ad)-mediated over-expression of trappin-2 (t-2) an antibacterial molecule with anti-inflammatory activity, increased mice survival following infection with the cerebral malaria-inducing plasmodium berghei anka (pbanka) strain. systemically, t-2 reduced pba ...201728181563
cellular stress associated with the differentiation of plasmodium berghei ookinetes.for malaria transmission, plasmodium parasites must develop in the mosquito vector. oxidative stress in the insect midgut, triggered by environmental changes (e.g., ph and temperature), influences the cellular signaling involved in differentiation from gametocytes to mobile ookinetes for the purpose of parasite survival. oxidative stress activates the homeostatic response to stress characterized by the phosphorylation eif2α, the attenuation of protein synthesis, and the transcription of genes pa ...201728177775
the antimalarial effect of curcumin is mediated by the inhibition of glycogen synthase kinase-3β.curcumin, a bioactive compound in curcuma longa, exhibits various pharmacological activities, including antimalarial effects. in silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (gsk3β)-inhibitory properties. the involvement of gsk3 in the antimalarial effects in vivo is yet to be demonstrated. in this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host gsk3β. intraperitoneal administration of curcu ...201728146408
plasmodium berghei exp-1 interacts with host apolipoprotein h during plasmodium liver-stage development.the first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. hepatic plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (pv). here, we show that, during the parasite's hepatic replication, the c-terminal region of the parasitic pv membrane pro ...201728137845
increased cd11b and hypoxia-inducible factors-1alpha expressions in the lung tissue and surfactant protein-d levels in serum are related with acute lung injury in severe malaria of c57bl/6 mice.we aimed to reveal the role of cd11b and hypoxia-inducible factors-1alpha (hif-1α) expressions on monocytes and alveolar macrophages of lung tissue, and the levels of serum surfactant protein-d (sp-d) in severe malaria-associated acute lung injury (ali).201728127335
sex-specific biology of the human malaria parasite revealed from the proteomes of mature male and female gametocytes.the gametocytes of the malaria parasites are obligate for perpetuating the parasite's life cycle through mosquitoes, but the sex-specific biology of gametocytes is poorly understood. we generated a transgenic line in the human malaria parasite plasmodium falciparum, which allowed us to accurately separate male and female gametocytes by flow cytometry. in-depth analysis of the proteomes by liquid chromatography-tandem mass spectrometry identified 1244 and 1387 proteins in mature male and female g ...201728126901
sequestration of cholesterol within the host late endocytic pathway restricts liver-stage plasmodium development.while lysosomes are degradative compartments and one of the defenses against invading pathogens, they are also hubs of metabolic activity. late endocytic compartments accumulate around plasmodium berghei liver-stage parasites during development, and whether this is a host defense strategy or active recruitment by the parasites is unknown. in support of the latter hypothesis, we observed that the recruitment of host late endosomes (les) and lysosomes is reduced in uis4(-) parasites, which lack a ...201728122820
grammomys surdaster, the natural host for plasmodium berghei parasites, as a model to study whole-organism vaccines against malaria.inbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. to establish a more rigorous animal model, we acquired african woodland thicket rats of the genus grammomys, the natural hosts for plasmodium berghei thicket rats were acquired and identified as grammomys surdaster by skull and teeth measurements and mitochondrial dna genotyping. herein, we demonstrate that thicket rats are highly susceptible to infection by p berghei, an ...201728115674
motility precedes egress of malaria parasites from oocysts.malaria is transmitted when an infected anopheles mosquito deposits plasmodium sporozoites in the skin during a bite. sporozoites are formed within oocysts at the mosquito midgut wall and are released into the hemolymph, from where they invade the salivary glands and are subsequently transmitted to the vertebrate host. we found that a thrombospondin-repeat containing sporozoite-specific protein named thrombospondin-releated protein 1 (trp1) is important for oocyst egress and salivary gland invas ...201728115054
pharmacomodulation of the antimalarial plasmodione: synthesis of biaryl- and n-arylalkylamine analogues, antimalarial activities and physicochemical properties.with the aim of increasing the structural diversity on the early antimalarial drug plasmodione, an efficient and versatile procedure to prepare a series of biaryl- and n-arylalkylamines as plasmodione analogues is described. using the naturally occurring and commercially available menadione as starting material, a 2-step sequence using a kochi-anderson reaction and subsequent pd-catalyzed suzuki-miyaura coupling was developed to prepare three representative biphenyl derivatives in good yields fo ...201728106855
impact of extended duration of artesunate treatment on parasitological outcome in a cytocidal murine malaria model.artemisinin-based combination therapies are a key pillar in global malaria control and are recommended as a first-line plasmodium falciparum treatment. they rely upon a rapid 4-log-unit reduction in parasitemia by artemisinin compounds with a short half-life and the killing of remaining parasites by a partner compound with a longer half-life. current treatment guidelines stipulate giving three 24-h-interval doses or six 12-h-interval doses over a 3-day period. due to the short half-life of artes ...201728096162
platelets activate a pathogenic response to blood-stage plasmodium infection but not a protective immune response.clinical studies indicate that thrombocytopenia correlates with the development of severe falciparum malaria, suggesting that platelets either contribute to control of parasite replication, possibly as innate parasite killer cells or function in eliciting pathogenesis. removal of platelets by anti-cd41 mab treatment, platelet inhibition by aspirin, and adoptive transfer of wild-type (wt) platelets to cd40-ko mice, which do not control parasite replication, resulted in similar parasitemia compare ...201728096086
the threshold of protection from liver-stage malaria relies on a fine balance between the number of infected hepatocytes and effector cd8(+) t cells present in the liver.since the demonstration of sterile protection afforded by injection of irradiated sporozoites, cd8(+) t cells have been shown to play a significant role in protection from liver-stage malaria. this is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. we used an adoptive transfer model to elucidate the kinetics of the effect ...201728087668
cloning, characterization and transmission blocking potential of midgut carboxypeptidase a in anopheles stephensi.transmission-blocking vaccines (tbv) interrupt malaria parasite transmission and hence form an important component for malaria eradication. mosquito midgut exopeptidases such as aminopeptidase n & carboxypeptidase b have demonstrated tbv potential. in the present study, we cloned and characterized carboxypeptidase a (cpa) from the midgut of an important malarial vector, anopheles stephensi. clustalw amino acid alignment and in silico 3-dimensional structure analysis of cpa predicted the presence ...201728087198
in vivo antiplasmodial activity and toxicological assessment of hydroethanolic crude extract of ajuga remota.malaria is one of the most life-threatening health problems worldwide and treatment has been compromised by drug resistance. identifying lead molecules from natural products might help to find better anti-malarial drugs, since those obtained from natural sources are still effective against malarial parasites. this study aimed at investigating the in vivo antiplasmodial activity of crude extract of the leaves of ajuga remota together with its safety in mice models.201728086782
a knockout screen of apiap2 genes reveals networks of interacting transcriptional regulators controlling the plasmodium life cycle.a family of apicomplexa-specific proteins containing ap2 dna-binding domains (apiap2s) was identified in malaria parasites. this family includes sequence-specific transcription factors that are key regulators of development. however, functions for the majority of apiap2 genes remain unknown. here, a systematic knockout screen in plasmodium berghei identified ten apiap2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three wer ...201728081440
modulation of host cell sumoylation facilitates efficient development of plasmodium berghei and toxoplasma gondii.sumoylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport, and protein-protein interactions. several viruses and bacteria modulate host sumoylation machinery for efficient infection. plasmodium sporozoites are infective forms of malaria parasite that invade mammalian hepatocytes and transforms into exoerythrocytic forms (eefs). here, we show that during eef development, the distribution of sumoylated proteins in host ...201728078755
a novel and conserved plasmodium sporozoite membrane protein speld is required for maturation of exo-erythrocytic forms.plasmodium sporozoites are the infective forms of malaria parasite to vertebrate host and undergo dramatic changes in their transcriptional repertoire during maturation in mosquito salivary glands. we report here the role of a novel and conserved plasmodium berghei protein encoded by pbanka_091090 in maturation of exo-erythrocytic forms (eefs) and designate it as sporozoite surface protein essential for liver stage development (pbspeld). pbanka_091090 was previously annotated as pb402615.00.0 an ...201728067322
antimalarial activity of syzygium guineense during early and established plasmodium infection in rodent models.in ethiopia, the leaves of syzygium guineense have been found useful for the prevention and cure of malaria, and demonstrated antiplasmodial activity in vitro. nevertheless, no scientific study has been conducted to confirm its antimalarial activity in vivo. therefore, the objective of the study was to evaluate the antimalarial effect of syzygium guineense leaf extract in mice.201728056963
in vivo antimalarial activity of crude extracts and solvent fractions of leaves of strychnos mitis in plasmodium berghei infected mice.malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-saharan africa. today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. medicinal plants are the unquestionable source of effective antimalarials. the present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant strychnos mitis in plasmodium berghei infected mice.201728056932
in vitro and in vivo antimalarial potential of oleoresin obtained from copaifera reticulata ducke (fabaceae) in the brazilian amazon rainforest.in view of the wide variety of the flora of the amazon region, many plants have been studied in the search for new antimalarial agents. copaifera reticulata is a tree distributed throughout the amazon region which contains an oleoresin rich in sesquiterpenes and diterpenes with β-caryophyllene as the major compound. the oleoresin has demonstrated antiparasitic activity against leishmania amazonensis. because of this previously reported activity, this oleoresin would be expected to also have anti ...201728160850
activation and exhaustion of antigen-specific cd8(+) t cells occur in different splenic compartments during infection with plasmodium berghei.the spleen is the major organ in which t cells are primed during infection with malaria parasites. however, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. we examined murine cd8(+) t cell responses during infection with plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (ova) protein and compared the responses with those elicited by listeria monocytogenes expressing the sam ...201728163249
the mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging.a wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. hence observation of these regions has wide application to understanding host-pathogen interactions. interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with ...201728351758
evaluation of plasmodium vivax cell-traversal protein for ookinetes and sporozoites as a preerythrocytic p. vivax vaccine.four different vaccine platforms, each targeting the human malaria parasite plasmodium vivax cell-traversal protein for ookinetes and sporozoites (pvceltos), were generated and assessed for protective efficacy. these platforms consisted of a recombinant chimpanzee adenoviral vector 63 (chad63) expressing pvceltos (ad), a recombinant modified vaccinia virus ankara expressing pvceltos (mva), pvceltos conjugated to bacteriophage qβ virus-like particles (vlps), and a recombinant pvceltos protein exp ...201728179403
transient expression of plasmodium berghei msp8 and hap2 in the marine protozoan parasite perkinsus marinus.perkinsus marinus is a protozoan parasite of molluscs that can be propagated in vitro in a defined culture medium, in the absence of host cells. we previously reported that p. marinus trophozoites can be transfected with high efficiency by electroporation using a plasmid based on moe, a highly expressed gene, and proposed its potential use as a "pseudoparasite." this is a novel gene expression platform for parasites of medical relevance for which the choice of the surrogate organism is based on ...201727723436
evidence of cross-stage cd8+ t cell epitopes in malaria pre-erythrocytic and blood stage infections.malaria parasites have a complex, multi-stage life cycle, and there is a widely held view that each stage displays a distinct set of antigens presented to the immune system. yet, molecular analysis of malaria parasites suggests that many putative antigenic targets are shared amongst the different stages. the specificities of these cross-stage antigens and the functions of the immune responses they elicit are poorly characterised. it is well known that cd8+ t cells play opposing immune functions ...201728380250
a novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions.transmission-blocking interventions (tbis) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. tbis include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. accurate methodologies are key to assess tbi efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. measuring intervention e ...201728376897
preferentially expanding vγ1(+) γδ t cells are associated with protective immunity against plasmodium infection in mice.γδ t cells play a crucial role in controlling malaria parasites. dendritic cell (dc) activation via cd40 ligand (cd40l)-cd40 signaling by γδ t cells induces protective immunity against the blood-stage plasmodium berghei xat (pbxat) parasites in mice. however, it is unknown which γδ t-cell subset has an effector role and is required to control the plasmodium infection. here, using antibodies to deplete tcr vγ1(+) cells, we saw that vγ1(+) γδ t cells were important for the control of pbxat infecti ...201728012161
sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance.the present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (al) from a nanostructured lipid carrier (nlc) of lumefantrine (lum) and estimate the potential of al as an oral delivery system in malariogenic wistar mice. lum-nlcs were prepared by hot homogenization using precirol(®) ato 5/transcutol(®) hp and tallow fat/transcutol(®) hp optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. lum-nlc characteristics, ...201727932882
the plasmodium falciparum cell-traversal protein for ookinetes and sporozoites as a candidate for preerythrocytic and transmission-blocking vaccines.recent studies have shown that immune responses against the cell-traversal protein for plasmodium ookinetes and sporozoites (celtos) can inhibit parasite infection. while these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the plasmodium falciparum celtos in vivo using a newly developed rodent malaria chimeric parasite expressing the p. falciparum celtos (pfceltos), we evaluated the protective ...201727895131
progress in imaging methods: insights gained into plasmodium biology.over the past decade, major advances in imaging techniques have enhanced our understanding of plasmodium spp. parasites and their interplay with mammalian hosts and mosquito vectors. cryoelectron tomography, cryo-x-ray tomography and super-resolution microscopy have shifted paradigms of sporozoite and gametocyte structure, the process of erythrocyte invasion by merozoites, and the architecture of maurer's clefts. intravital time-lapse imaging has been revolutionary for our understanding of pre-e ...201727890922
antiplasmodial activity of heinsia crinita (rubiaceae) and identification of new iridoids.heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. its stem bark powder is found in some peripheral markets in the democratic republic of the congo (drc) as a remedy against malaria. investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties.201727890637
differences in the modulation of reactive species, lipid bodies, cyclooxygenase-2, 5-lipoxygenase and ppar-γ in cerebral malaria-susceptible and resistant mice.proinflammatory responses are associated with the severity of cerebral malaria. no, h2o2, eicosanoid and ppar-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. this work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible cba and c57bl/6 and -resistant balb/c mice. mice were infected with plasmodium berghei anka, and the survival rates and parasitemia curves were assessed. on the sixth day post-infection, ...201727887739
usp15 regulates type i interferon response and is required for pathogenesis of neuroinflammation.genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. we identified a mutation in the gene encoding the deubiquitination enzyme usp15 (usp15(l749r)) that protected mice against both experimental cerebral malaria (ecm) induced by plasmodium berghei and experimental autoimmune encephalomyelitis (eae). c ...201727721430
uptake of parasite-derived vesicles by astrocytes and microglial phagocytosis of infected erythrocytes may drive neuroinflammation in cerebral malaria.astrocytes and microglia are activated during cerebral malaria (cm) and contribute to the production and release of several mediators during neuroinflammatory processes. whether these changes are the consequence of a direct crosstalk between glial cells and the malarial parasite and how these cells participate in the pathogenesis of cm is not yet clear. we therefore examined the interaction of astrocytes and microglia with plasmodium berghei anka-infected red blood cells using primary cell cultu ...201727696532
the evolutionary divergence of stat transcription factor in different anopheles species.anopheles mosquito transmits plasmodium, the malaria causing parasite. different species of anopheles mosquito dominate in a particular geographical location and are capable of transmitting specific strains of plasmodium. it is important to understand the biology of different anophelines to control the parasite transmission. stat is an evolutionary conserved transcription factor that regulates the parasite development in african malaria vector anopheles gambiae. unlike drosophila and aedes aegyp ...201727664587
glut1-mediated glucose uptake plays a crucial role during plasmodium hepatic infection.intracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite plasmodium berghei and that glucose uptake via the glut1 transporter is specifically enhanced in p. berghei-infected cells. we further show that atp levels of cells containing developing parasites are decreased, which is known to enhance membrane glut1 activity. in addition, glut1 mo ...201727404888
antimalarial activity of fractions of aqueous extract of acacia nilotica root.the problem of resistance of malarial parasites to available antimalarial drugs makes the development of new drugs imperative, with natural plant products providing an alternative source for discovering new drugs.201727104040
controlled release of artemisone for the treatment of experimental cerebral malaria.cerebral malaria (cm) is a leading cause of malarial mortality resulting from infection by plasmodium falciparum. treatment commonly involves adjunctive care and injections or transfusion of artemisinins. all artemisinins that are in current use are metabolized to dihydroxyartemisinin (dha), to which there is already some parasite resistance. we used artemisone, a derivative that does not convert to dha, has improved pharmacokinetics and anti-plasmodial activity and is also anti-inflammatory (an ...201728249591
minocycline prevents cerebral malaria, confers neuroprotection and increases survivability of mice during plasmodium berghei anka infection.cerebral malaria (cm) is a neurological complication arising due to plasmodium falciparum or plasmodium vivax infection. minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. in this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ecm). the currently accepted mouse model, c57bl/6 mice infected with plasmodium berghei anka, was used fo ...201727865203
antiplasmodial activity of the ethanolic root bark extract of icacina senegalensis in mice infected by plasmodium berghei.the root of icacina senegalensis is used for the treatment of malaria and related conditions in southeastern nigeria.201727845882
antiplasmodial, antioxidant and immunomodulatory activities of ethanol extract of vernonia amygdalina del. leaf in swiss mice.vernonia amygdalina (v. amygdalina) leaf is locally employed in the southern region of nigeria in the treatment of malaria infection. this study evaluated the in vivo antiplasmodial, antioxidant and immunomodulatory effect of ethanol extract of v. amygdalina leaf.201727222837
parasitemia induces high plasma levels of interleukin-17 (il-17) and low levels of interleukin-10 (il-10) and transforming growth factor-ß (tgf-ß) in pregnant mice infected with malaria.during pregnancy, the balanced dominance of the t helper17 response shifts to a th2 response that is characterised by the production of il-10, following the completion of the implantation process. transforming growth factor-β (tgf-β) expression is associated with the completion of trophoblast invasion and placental growth. this study assessed the effect of malaria infection on the levels of il-17, il-10, and tgf-β in the plasma of pregnant mice with malaria.201726715893
novel metalloantimalarials: transmission blocking effects of water soluble cu(i), ag(i) and au(i) phosphane complexes on the murine malaria parasite plasmodium berghei.the water soluble phosphane complexes [m(l)4]pf6 (m=cu(i), ag(i)) and [au(l)4]cl (l=thp (tris(hydroxymethyl)phosphane) or pta (1,3,5-triaza-7-phosphaadamantane)) showed notable in vitro activity against plasmodium early sporogonic stages, the sexual forms of the malaria parasite that are responsible for infection of the mosquito vector. effects varied according to both, the type of metal and phosphane ligands. [ag(thp)4]pf6 was the best performing complex exhibiting a half inhibitory concentrati ...201727815977
tacrolimus prevents murine cerebral malaria.tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transplantation. tacrolimus is also reported to inhibit plasmodium falciparum growth in vitro. here, we report that tacrolimus prevented the death from cerebral malaria of plasmodium berghei anka-infected c57bl/6j mice, but not their death from malaria due to the high parasitaemia and severe anaemia. the mycophenolate mofetil-treated mice showed higher mortality from cerebral malaria and succumbed to malar ...201727546479
in vivo antimalarial activity of extracts of tanzanian medicinal plants used for the treatment of malaria.plants used in traditional medicine have been the source of a number of currently used antimalarial medicines and continue to be a promising resource for the discovery of new classes of antimalarial compounds. the aim of this study was to evaluate in vivo antimalarial activity of four plants; erythrina schliebenii harms, holarrhena pubescens buch-ham, phyllanthus nummulariifolius poir, and caesalpinia bonducella (l.) flem used for treatment of malaria in tanzania. in vivo antimalarial activity w ...201727144154
in vivo antimalarial activities of russelia equisetiformis in plasmodium berghei infected mice.the rising problem of resistance to most commonly used antimalarials remains a major challenge in the control of malaria suggesting the need for new antimalarial agents. this work explores the antiplasmodial potential of ethanol extract of russelia equisetiformis in chloroquine plasmodium berghei infected mice. swiss albino mice were intraperitoneally infected with chloroquine-resistant p. berghei (anka). experimental mice were treated for four days consecutively with graded doses of plant extra ...201726664070
interleukin-18 antagonism improved histopathological conditions of malaria infection in mice.interleukin 18 (il-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. previous studies have demonstrated the promising therapeutic potential of modulating il-18 bioactivity in various pathological conditions. however, its involvement during malaria infection has yet to be established. in this study, we demonstrated the effect of modulating il-18 on the histopathological conditions of malaria infected mice.201726622294
anti-plasmodial activity of ethanolic extract of root and stem back of cassia sieberiana dc on mice.this study assessed within 4 days of suppressive test in vivo antimalarial activity of ethanolic extract of root and stem bark of cassia sieberiana dc against chloroquine sensitive strain of plasmodium berghei nk65 in mice.201726401393
antimalarial evaluation of the leaf latex of aloe citrina and its major constituent.malaria is one of the major obstacles to the socioeconomic development of several developing countries. adequate treatment of the disease is becoming increasingly difficult due to the worsening problems of drug resistance in many parts of the world. therefore, increased efforts in antimalarial drug discovery are urgently needed.201726120228
yeast lysates carrying the nucleoprotein from measles virus vaccine as a novel subunit vaccine platform to deliver plasmodium circumsporozoite antigen.yeast cells represent an established bioreactor to produce recombinant proteins for subunit vaccine development. in addition, delivery of vaccine antigens directly within heat-inactivated yeast cells is attractive due to the adjuvancy provided by the yeast cell. in this study, pichia pastoris yeast lysates carrying the nucleoprotein (n) from the measles vaccine virus were evaluated as a novel subunit vaccine platform to deliver the circumsporozoite surface antigen (cs) of plasmodium. when expres ...201728662722
virus-like particle (vlp) plus microcrystalline tyrosine (mct) adjuvants enhance vaccine efficacy improving t and b cell immunogenicity and protection against plasmodium berghei/vivax.vaccination is the most effective prophylactic tool against infectious diseases. despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. microcrystalline tyrosine (mct) is a well described depot used in licensed allergy immunotherapy products and in clinical development. however, its proof of concept in prophylactic vaccines has only recently been explored. mct has never been used in combination with virus-like particles (vlps), whic ...201728468322
in vivo imaging of pathogen homing to the host tissues.hematogenous dissemination followed by tissue tropism is a characteristic of the infectious process of many pathogens including those transmitted by blood-feeding vectors. after entering into the blood circulation, these pathogens must arrest in the target organ before they infect a specific tissue. here, we describe a non-invasive method to visualize and quantify the homing of pathogens to the host tissues. by using in vivo bioluminescence imaging we quantify the accumulation of luciferase-expr ...201728522323
antecedent nippostrongylus infection alters the lung immune response to plasmodium berghei.in endemic regions, it is not uncommon for patients to be co-infected with soil-transmitted helminths and malaria. although both malaria and many helminth species use the lungs as a site of development, little attention has been paid to the impact that pulmonary immunity induced by one parasite has on the lung response to the other. to model the consequences of a prior hookworm exposure on the development of immunity to malaria in the lungs, mice were infected with nippostrongylus brasiliensis a ...201728475238
a plasmodium plasma membrane reporter reveals membrane dynamics by live-cell microscopy.during asexual replication within the anopheles mosquito and their vertebrate host, plasmodium parasites depend on the generation of a massive amount of new plasma membrane to produce thousands of daughter parasites. how the parasite plasma membrane (ppm) is formed has mostly been studied by electron microscopy, which does not allow an insight into the dynamics of this process. we generated a plasmodium berghei reporter parasite line by gfp-tagging of a non-essential ppm-localized protein, and f ...201728851956
multifunctional involvement of a c2h2 zinc finger protein (pbzfp) in malaria transmission, histone modification, and susceptibility to dna damage response.in sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. the quest for understanding regulatory mechanisms of meiotic recombination in plasmodium led to identification of a gene encoding a protein that contains 11 copies of c2h2 zinc fingers (znf). reverse genetic approaches were used to create plasmodium berghei parasites either lacking expression of full-length plasmodium berghei zinc finger protein (pbzfp) (knock ...201728851851
preparation and in vivo evaluation of anti-plasmodial properties of artemisinin loaded pcl-peg-pcl nanoparticles.artemisinin (art) has anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and anti-malarial effects, but its application is limited due to its low water solubility and poor oral bioavailability. in this study, the bioavailability, water solubility and anti-plasmodial property of art were improved by pcl-peg-pcl triblock copolymers.201728851256
antioxidant defense system induced by cysteine-stabilized peptide fraction of aqueous extract of morinda lucida leaf in selected tissues of plasmodium berghei-infected mice.this study evaluated the responses of some antioxidant parameters in selected tissues of plasmodium berghei-infected mice treated with cysteine-stabilized peptide fraction (cspf) of aqueous extract of morinda lucida leaf.201728844216
chemopreventive and remediation effect of adansonia digitata l. baobab (bombacaceae) stem bark extracts in mouse model malaria.adansonia digitata l. baobab (bombacaceae) solvent extracts have been reported to possess medicinal properties and are currently been used traditionally for the treatment of malaria and several other diseases and infection; however few reports exist in literature that provides supportive scientific evidence in favour of its medicinal use.201728843893
perillyl alcohol exhibits in vitro inhibitory activity against plasmodium falciparum and protects against experimental cerebral malaria.the development of new drugs is one of the strategies to control malaria. isoprenoid biosynthesis in plasmodium falciparum is an essential pathway for parasite survival, and therefore a potential target for new antimalarial drugs. indeed, plant-derived secondary metabolites such as terpenes exhibit antimalarial activity in vitro by inhibiting isoprenoid biosynthesis in p. falciparum. in this study, the in vitro antiplasmodial activity of perillyl alcohol (poh) was evaluated, along with its in vi ...201728843818
dysregulation of limk-1/cofilin-1 pathway: a possible basis for alteration of neuronal morphology in experimental cerebral malaria.loss of cognition even after survival is the salient feature of cerebral malaria (cm). currently, the fate of neuronal morphology is not studied at the ultra-structural level in cm. recent studies suggest that maintenance of neuronal morphology and dendritic spine density (actin dynamics in particular) are essential for proper cognitive functions. limk-1/cofilin-1signaling pathway is known to involve in the maintenance of actin dynamics through regulation of cofilin-1, in executing learning and ...201728843047
plasmodium berghei cap93, a novel oocyst capsule-associated protein, plays a role in sporozoite development. 201728841886
inverted recruitment of autophagy proteins to the plasmodium berghei parasitophorous vacuole membrane.selective autophagy and related mechanisms can act as variable defense mechanisms against pathogens and can therefore be considered as intracellular immune responses. when in hepatocytes, plasmodium parasites reside in a parasitophorous vacuole (pv) and the pv membrane (pvm) is the main contact site between host cell and parasite. early in infection, the pvm is directly labeled with host cell autophagy proteins lc3b and p62 (nucleoporin 62). we investigated the recruitment of different selective ...201728841718
phenotypic approach artemisinin resistance in malaria rodent as in vivo model.the aim of this study is to prove the development of artemisinin resistance phenotypically in malaria rodent as an in vivo resistance development model in humans.201728831224
immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (hrf) of the parasite.while most subunit malaria vaccines provide only limited efficacy, pre-erythrocytic and erythrocytic genetically attenuated parasites (gap) have been shown to confer complete sterilizing immunity. we recently generated a plasmodium berghei (pbnk65) parasite that lacks a secreted factor, the histamine releasing factor (hrf) (pbnk65 hrfδ), and induces in infected mice a self-resolving blood stage infection accompanied by a long lasting immunity. here, we explore the immunological mechanisms underl ...201728831137
down-regulation of tim-3 in monocytes and macrophages in plasmodium infection and its association with parasite clearance.t-cell immunoglobulin and mucin-domain-containing molecule 3 (tim-3) has complicated roles in regulating monocytes and macrophages in various diseases and it tends to be an inhibitory molecule to facilitate the immune escape of parasites in malaria. however, the mechanisms of tim-3 mediated responses in monocytes and macrophages in malaria have not been clear. in this study, we found that plasmodium infection down-regulated tim-3 expression in peripheral monocytes of patients suffering from plas ...201728824565
tlr4-mediated placental pathology and pregnancy outcome in experimental malaria.malaria-associate pregnancy has a significant impact on infant morbidity and mortality. the detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. herein we sought to evaluate the effect of toll-like receptors (tlrs) activation on placental malaria (pm) development by using the plasmodium berghei nk65(gfp) infection model. we observed that activation of the innate immune system by parasites leads to pm due to local i ...201728819109
hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity.antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. here, we report the identification and characterization of hexahydroquinolines (hhqs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite plasmodium falciparum. this activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and re ...201728808258
reduction of mosquito survival in mice vaccinated with anopheles stephensi glucose transporter.despite the fact that recent efforts to control/eradicate malaria have contributed to a significant decrease in the number of cases and deaths, the disease remains a global health challenge. vaccines based on mosquito salivary gland antigens are a potential approach for reducing vector populations and malaria parasites. the anopheles agap007752 gene encodes for a glucose transporter that is upregulated during plasmodium infection, and its knockdown decreases the number of sporozoites in mosquito ...201728804714
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