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efficacy of recombinant canine distemper virus expressing leishmania antigen against leishmania challenge in dogs.canine distemper virus (cdv) vaccination confers long-term protection against cdv reinfection. to investigate the utility of cdv as a polyvalent vaccine vector for leishmania, we generated recombinant cdvs, based on an avirulent yanaka strain, that expressed leishmania antigens: lack, tsa, or lmsti1 (rcdv-lack, rcdv-tsa, and rcdv-lmsti1, respectively). dogs immunized with rcdv-lack were protected against challenge with lethal doses of virulent cdv, in the same way as the parental yanaka strain. ...201526162094
expression and purification of a new recombinant camel hepcidin able to promote the degradation of the iron exporter ferroportin1.hepcidin, a 25-amino-acid and highly disulfide bonded antimicrobial peptide, is the central regulator of iron homeostasis. this hormone is expressed in response to iron and inflammation and interacts with ferroportin1 (fpn1), the only known iron exporter in vertebrates, inducing its internalization and degradation. thus, the export of iron from cells to plasma will be significantly diminished. thereby, hepcidin has become the target of intense research studies due to its profound biomedical sign ...201526169129
rapd-pcr reveals genetic polymorphism among leishmania major strains from tunisian patients.zoonotic cutaneous leishmaniasis caused by leishmania (l.) major is endemoepidemic in the center and south of tunisia. the clinical course of the disease varies widely among different patients and geographic regions. although genetic diversity in l. major parasites has been suggested as a potential factor influencing their pathogenic variability, little information on genetic polymorphism among l. major strains is available in the literature. this work aimed to estimate the genetic variability w ...201526170197
taci deficiency leads to alternatively activated macrophage phenotype and susceptibility to leishmania infection.the tnf family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (taci), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. here, we report that compared with wt mouse, taci ko μϕs expressed lower levels of toll-like receptors (tlrs), cd14, myeloid differentiation primary response protein 88, and adaptor protein toll/il-1 receptor domain-containing adapter-inducing ifn-β and responded po ...201526170307
frequency of seropositivity against infectious agents amongst pemphigus vulgaris patients: a case-control study on strongyloides stercoralis, helicobacter pylori, toxoplasma gondii, leishmania major, and epstein-barr virus.environmental and genetic factors may contribute to the pathogenesis of pemphigus vulgaris (pv) as an autoimmune disease. we aimed to determine rates of seropositivity for immunoglobulin g (igg) antibodies against a number of infectious agents in untreated and treated pv patients and in healthy individuals.201526175264
an epidemiological study of cutaneous leishmaniasis using active case finding among elementary school students in pakdasht, southeast of tehran, iran 2013-2014.cutaneous leishmaniasis is one of the prevalent health problems in tropical and subtropical areas including iran. therefore, it is essential to identify the prevalence and new foci of this disease in different regions of iran. this study aimed to determine the epidemiology of cutaneous leishmaniasis by active surveillance in elementary schools in pakdasht city, southeast of tehran, iran 2013-2014.201526175293
recombinant leishmania major lipophosphoglycan 3 activates human t-lymphocytes via tlr2-independent pathway.leishmaniasis is one of the most common infectious diseases transmitted by an obligate intracellular genus leishmania. as there is no efficient vaccination strategy for leishmaniasis, new immunostimulatory components may enhance protective immune responses against this parasite. lipophosphoglycan 3 (lpg3) is an essential protein required for lpg assembling. in this study, the ability of recombinant lpg3 (rlpg) and its fragments to activate isolated healthy human t-cells and cytokine secretion wa ...201626181511
the lack of effectiveness of hyperbaric oxygenation as a treatment for leishmania major in a mouse model.we aimed to study the effectiveness of hyperbaric oxygen therapy (hot) (100% oxygen at 2 ata for 70 minutes each session for 20 consecutive days) on balb/c male mice infected with leishmania major. fifty-one mice were assigned to six groups. group 1 was treated with hot from 1 day after the inoculation. in groups 2-5, treatment began when the cutaneous lesions appeared. group 2 received hot only, group 3 received topical therapy with leshcutan only, groups 4 and 5 received a combination of hot a ...201526204005
leishmania major udp-sugar pyrophosphorylase salvages galactose for glycoconjugate biosynthesis.leishmaniases are a set of tropical and sub-tropical diseases caused by protozoan parasites of the genus leishmania whose severity ranges from self-healing cutaneous lesions to fatal visceral infections. leishmania parasites synthesise a wide array of cell surface and secreted glycoconjugates that play important roles in infection. these glycoconjugates are particularly abundant in the promastigote form and known to be essential for establishment of infection in the insect midgut and effective t ...201526215058
skin-resident memory cd4+ t cells enhance protection against leishmania major infection.leishmaniasis causes a significant disease burden worldwide. although leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. although circulating leishmania-specific t cells are known to play a critical role in immunity, the role of memory t cells present in peripheral tissues has not been explored. here, we identify a population of skin-resident leishmania-specific memory cd4+ t cells. thes ...201526216123
the proliferation potential of promastigotes of the main leishmania species of the old world in nnn culture medium prepared using blood of four different mammals.the efficacy of the in vitro cultivation of promastigotes of four leishmania spp. was tested in the biphasic novy-macneal-nicolle (nnn) medium prepared using blood from different animals (horse, donkey, goat and sheep). the aim was to test which nnn preparation gave the best yield in the shortest time for different parasite species, in order to obtain a large crop of promastigotes for experimental work and for antigen preparation. promastigotes of leishmania infantum, leishmania donovani, leishm ...201526219203
generation of an aquaglyceroporin aqp1 null mutant in leishmania major.the leishmania aquaglyceroporin aqp1 plays an important physiological role in water and uncharged polar solutes transport, volume regulation, osmotaxis, and is a key determinant of antimony resistance. by targeted gene disruption, we generated a leishmania major promastigote aqp1 null mutant. this required several attempts but a chromosomal null aqp1 mutant was obtained by loss of heterozygosity in the presence of a rescue plasmid encoding aqp1. growth in the absence of selection led to the loss ...201526222914
autophagic digestion of leishmania major by host macrophages is associated with differential expression of bnip3, ctse, and the mirnas mir-101c, mir-129, and mir-210.autophagy participates in innate immunity by eliminating intracellular pathogens. consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. in the current study, interactions between leishmania major (l. m.) and the autophagic machinery of bone marrow-derived macrophages (bmdm) were analyzed.201526226952
fitness and phenotypic characterization of miltefosine-resistant leishmania major.trypanosomatid parasites of the genus leishmania are the causative agents of leishmaniasis, a neglected tropical disease with several clinical manifestations. leishmania major is the causative agent of cutaneous leishmaniasis (cl), which is largely characterized by ulcerative lesions appearing on the skin. current treatments of leishmaniasis include pentavalent antimonials and amphotericin b, however, the toxic side effects of these drugs and difficulty with distribution makes these options less ...201526230675
natural infection of bats with leishmania in ethiopia.the leishmaniases, a group of diseases with a worldwide-distribution, are caused by different species of leishmania parasites. both cutaneous and visceral leishmaniasis remain important public health problems in ethiopia. epidemiological cycles of these protozoans involve various sand fly (diptera: psychodidae) vectors and mammalian hosts, including humans. in recent years, leishmania infections in bats have been reported in the new world countries endemic to leishmaniasis. the aim of this study ...201526232657
evaluation of apoptotic and antileishmanial activities of artemisinin on promastigotes and balb/c mice infected with leishmania major.in leishmaniasis, some drugs prescribed for treatment have toxic effects and there are reports about drug resistance in some countries. due to this fact, using herbal drugs such as artemisinin with good efficacy and low toxic effect might be suitable.201726246824
hoarseness as the presenting symptom of visceral leishmaniasis with muco-cutaneous lesions: a case report.herein, a 28-year-old man with hoarseness, skin and oral lesions is presented. at the time of admission, the patient had an erythematous plaque on his chin near his lower lip and an erythematous-violaceous plaque on his palate near the opening of the pharynx and 20 kg weight lost in last one year. the biopsy of his skin lesions by hematoxylin and eosin staining revealed an infiltration of the dermis by lymphoplasma and histiocytic cells with a loose granuloma formation suggestive of leishmaniasi ...201726246830
functional role of lysine 12 in leishmania major aqp1.leishmania major aquaglyceroporin (aqp1) is an adventitious metalloid channel that allows the bidirectional movement of arsenite and antimonite. here we demonstrate that aqp1 is subjected to proteasome-dependent degradation. treatment of leishmania promastigotes with the proteasome inhibitor mg132 resulted in increased aqp1 accumulation. site-directed mutagenesis in aqp1 revealed that alteration of lysine 12 to either alanine or arginine improves protein stability. aqp1 expression is stabilized ...201526259900
characterization of the b cell response to leishmania infection after anti-cd20 b cell depletion.anti-cd20 depletion therapies targeting b cells are commonly used in malignant b cell disease and autoimmune diseases. there are concerns about the ability of b cells to respond to infectious diseases acquired either before or after b cell depletion. there is evidence that the b cell response to existing or acquired viral infections is compromised during treatment, as well as the antibody response to vaccination. our laboratory has an experimental system using co-infection of c3h mice with both ...201526261496
antigenic profile of heat-killed versus thimerosal-treated leishmania major using sodium dodecyl sulfate-polyacrylamide gel electrophoresis.leishmania is a parasitic protozoan of trypanosomatidae family which causes a wide spectrum of diseases ranging from self-healing cutaneous lesions to deadly visceral forms. in endemic areas, field trials of different preparations of leishmania total antigen were tested as leishmaniasis vaccine. two preparations of killed leishmania major were produced in iran, which were heat-killed vaccine called autoclaved l. major (alm) and thimerosal-treated freeze-thawed vaccine called killed l. major (klm ...201526261830
exploring biochemical and functional features of leishmania major phosphoenolpyruvate carboxykinase.this work reports the first functional characterization of leishmanial pepck. the recombinant leishmania major enzyme (lmj_pepck) exhibits equivalent kcat values for the phosphoenolpyruvate (pep) and oxaloacetate (oaa) forming reactions. the apparent km towards oaa is 10-fold lower than that for pep, while the km values for adp and atp are equivalent. mutagenesis studies showed that d241, d242 and h205 of lmj_pepck like the homologous residues of all known pepcks are implicated in metal ions bin ...201526271440
efficacy of permethrin treated bed nets against leishmania major infected sand flies.insecticide treated nets (itns) are a potential tool to help control sand flies and prevent leishmaniasis. however, little is currently known about the response of leishmania infected sand flies to itns. in this study, phlebotomus duboscqi sand flies were infected with the parasite leishmania major. infected and noninfected sand flies were then evaluated against permethrin treated and untreated bed nets in a laboratory assay that required sand flies to pass through suspended netting material to ...201526276941
detection of leishmania major and leishmania tropica in domestic cats in the ege region of turkey.leishmaniosis is a group of diseases caused by different species of leishmania parasites in mammalian species. the aim of the present study was to investigate the presence of leishmania spp. dna in cats using real time polymerase chain reaction (rt-pcr) assays targeting internal transcribed spacer (its1) and heat-shock protein 70 gene (hsp70) regions with leishmania species-specific primers and probes. blood samples were collected from 147 cats (73 female; 74 male) in the endemic regions for zoo ...201526277567
identification, biochemical characterization, and in-vivo expression of the intracellular invertase bfra from the pathogenic parasite leishmania major.the parasitic life cycle of leishmania includes an extracellular promastigote stage that occurs in the gut of the insect vector. during that period, the sucrose metabolism and more specifically the first glycosidase of this pathway are essential for growth and survival of the parasite. we investigated the expression of the invertase bfra in the promastigote and amastigote stages of three parasite species representative of the three various clinical forms and of various geographical areas, namely ...201526279524
assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in l. major infected balb/c mice.patients affected by cutaneous leishmaniasis need a topical treatment which cures lesions without leaving scars. lesions are produced not only by the parasite but also by an uncontrolled and persistent inflammatory immune response. in this study, we proposed the loading of β-lapachone (β-lp) in lecithin-chitosan nanoparticles (np) for targeting the drug to the dermis, where infected macrophages reside, and promote wound healing. although the loading of β-lp in np did not influence the drug antil ...201526282379
lymphocytic choriomeningitis virus expands a population of nkg2d+cd8+ t cells that exacerbates disease in mice coinfected with leishmania major.leishmaniasis is a significant neglected tropical disease that is associated with a wide range of clinical presentations and a lifelong persistent infection. because of the chronic nature of the disease, there is a high risk for coinfection occurring in patients, and how coinfections influence the outcome of leishmaniasis is poorly understood. to address this issue, we infected mice with leishmania major and 2 wk later with lymphocytic choriomeningitis virus (lcmv) and then monitored the course ...201526290604
the structure of the holo-acyl carrier protein of leishmania major displays a remarkably different phosphopantetheinyl transferase binding interface.the genome of leishmania major encodes a type ii fatty acid biosynthesis pathway for which no structural or biochemical information exists. here, for the first time, we have characterized the central player of the pathway, the acyl carrier protein (lmacp), using nuclear magnetic resonance (nmr). structurally, the lmacp molecule is similar to other type ii acps, comprising a four-helix bundle, enclosing a hydrophobic core. dissimilarities in sequence, however, exist in helix ii (recognition helix ...201526293213
leishmania tarentolae secreting the sand fly salivary antigen ppsp15 confers protection against leishmania major infection in a susceptible balb/c mice model.cutaneous leishmaniasis is a zoonotic, vector-borne disease causing a major health problem in several countries. no vaccine is available and there are limitations associated with the current therapeutic regimens. immune responses to sand fly saliva have been shown to protect against leishmania infection. a cellular immune response to ppsp15, a protein from the sand fly phlebotomus papatasi, was sufficient to control leishmania major infection in mice. this work presents data supporting the vacci ...201526298575
identification of immunodominant leishmania major antigenic markers of the early c57bl/6 and balb/c mice infection stages.the c57bl/6 mouse strain is resistant to leishmania (l.) major infection and, unlike susceptible balb/c, develops small self healing cutaneous lesions. the specific antibody responses of c57bl/6 and balb/c mice were previously characterized by the predominance of igg2a ("resistant" isotype associated with th1) and igg1 ("pathogenic" isotype associated with th2) antibodies, respectively. in this study, we looked for the presence of antigens able to elicit an exclusive or predominant igg1 producti ...201526299940
spatio-temporal genetic structuring of leishmania major in tunisia by microsatellite analysis.in tunisia, cases of zoonotic cutaneous leishmaniasis caused by leishmania major are increasing and spreading from the south-west to new areas in the center. to improve the current knowledge on l. major evolution and population dynamics, we performed multi-locus microsatellite typing of human isolates from tunisian governorates where the disease is endemic (gafsa, kairouan and sidi bouzid governorates) and collected during two periods: 1991-1992 and 2008-2012. analysis (f-statistics and bayesian ...201526302440
interaction of macrophage antigen 1 and cd40 ligand leads to il-12 production and resistance in cd40-deficient mice infected with leishmania major.although some studies indicate that the interaction of cd40 and cd40l is critical for il-12 production and resistance to cutaneous leishmaniasis, others suggest that this pathway may be dispensable. in this article, we compared the outcome of leishmania major infection in both cd40- and cd40l-deficient mice after treatment with ril-12. we show that although cd40 and cd40l knockout (ko) mice are highly susceptible to l. major, treatment with ril-12 during the first 2 wk of infection causes resolu ...201526304989
in vitro infectivity assessment by drug susceptibility comparison of recombinant leishmania major expressing enhanced green fluorescent protein or egfp-luciferase fused genes with wild-type parasite.leishmaniasis is a worldwide uncontrolled parasitic disease due to the lack of effective drug and vaccine. to speed up effective drug development, we need powerful methods to rapidly assess drug effectiveness against the intracellular form of leishmania in high throughput assays. reporter gene technology has proven to be an excellent tool for drug screening in vitro. the effects of reporter proteins on parasite infectivity should be identified both in vitro and in vivo. in this research, we init ...201526323836
intracellular survival of leishmania major depends on uptake and degradation of extracellular matrix glycosaminoglycans by macrophages.leishmania parasites replicate within the phagolysosome compartment of mammalian macrophages. although leishmania depend on sugars as a major carbon source during infections, the nutrient composition of the phagolysosome remains poorly described. to determine the origin of the sugar carbon source in macrophage phagolysosomes, we have generated a n-acetylglucosamine acetyltransferase (gnat) deficient leishmania major mutant (∆gnat) that is auxotrophic for the amino sugar, n-acetylglucosamine (glc ...201526334531
potential application of nanochitosan film as a therapeutic agent against cutaneous leishmaniasis caused by l. major.antileishmanial drugs traditionally used for treatment of cutaneous leishmaniasis are mainly toxic, ineffective for some parasite isolates, and costly. since chitosan is reported to accelerate wound healing, the aims of this study were to assess the effectiveness of nanochitosan films in the treatment of cutaneous leishmaniasis caused by leishmania major (iranian strain) and to investigate alterations of antioxidant enzyme activities and malondialdehyde levels. six weeks after l. major inoculati ...201526346452
unusual forms of cutaneous leishmaniasis due to leishmania major.cutaneous leishmaniasis (cl) due to leishmania major (l. major) is common in the middle east; however, this skin infection may be under-diagnosed when it presents atypically.201626347371
ultraviolet b efficacy in improving antileishmanial effects of silver nanoparticles.cutaneous leishmaniasis (cl) is a parasitic disease caused by various species of the flagellated protozoan, leishmania. regardless of the numerous studies, there are still serious challenges in the treatment of cl. this study aimed at evaluating the influence of a low dose ultraviolet b (uvb) radiation along with silver nanoparticles (agnps) on a mouse model of cl induced by leishmania major.201526351559
synthesis and evaluation of dna based quantum dot fluorescence in situ hybridization (fish) probe for telomere detection.efficient oligonucleotide probe design and synthesis based on polymer-coated cdse/zns quantum dot (qd) is demonstrated for detection of telomeres in human monocyte and leishmania major, a protozoan pathogenic parasite. the highly photoluminescent polymer-coated qds conjugated with various length of telomere probe sequences were prepared via carbodiimide chemistry and characterized. specific detection of telomere was observed when dna sequence was (cccaat)n (n = 5 or 3) probe sequence, rather tha ...201526353719
validation of recombinant salivary protein ppsp32 as a suitable marker of human exposure to phlebotomus papatasi, the vector of leishmania major in tunisia.during a blood meal, female sand flies, vectors of leishmania parasites, inject saliva into the host skin. sand fly saliva is composed of a large variety of components that exert different pharmacological activities facilitating the acquisition of blood by the insect. importantly, proteins present in saliva are able to elicit the production of specific anti-saliva antibodies, which can be used as markers for exposure to vector bites. serological tests using total sand fly salivary gland extracts ...201526368935
cutaneous infection with leishmania major mediates heterologous protection against visceral infection with leishmania infantum.visceral leishmaniasis (vl) is a fatal disease of the internal organs caused by the eukaryotic parasite leishmania. control of vl would best be achieved through vaccination. however, this has proven to be difficult partly because the correlates of protective immunity are not fully understood. in contrast, protective immunity against nonfatal cutaneous leishmaniasis (cl) is well defined and mediated by rapidly recruited, ifn-γ-producing ly6c(+)cd4(+) t cells at the dermal challenge site. protecti ...201526371247
synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines.a series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the c-8 position, was synthesized and evaluated for their antileishmanial activities. two derivatives exhibited very good activity against the promastigote and the amastigote forms of leishmania major in the micromolar to submicromolar ranges, coupled with a low cytotoxicity against macrophages and 3t3 mouse fibroblast cells. through lmck1 inhibition assay, investigations of ...201526383125
development of small-molecule trypanosoma brucei n-myristoyltransferase inhibitors: discovery and optimisation of a novel binding mode.the enzyme n-myristoyltransferase (nmt) from trypanosoma brucei has been validated both chemically and biologically as a potential drug target for human african trypanosomiasis. we previously reported the development of some very potent compounds based around a pyrazole sulfonamide series, derived from a high-throughput screen. herein we describe work around thiazolidinone and benzomorpholine scaffolds that were also identified in the screen. an x-ray crystal structure of the thiazolidinone hit ...201526395087
indigenous microbiota and leishmaniasis.animals are colonized by their indigenous microbiota from the early days of life. the estimated number of associated bacterial cells in humans is around of 10(14) per individual, most of them in the gut. several studies have investigated the microbiota-host relationship, and the use of germfree animals has been an important tool in these studies. these animals, when infected with a pathogen, have shown to be sometimes more resistant and other times more susceptible than conventional animals. lei ...201626407073
novel arylalkylamine compounds exhibits potent selective antiparasitic activity against leishmania major.leishmania major (l. major) is a protozoan parasite causal agent of leishmaniasis. it is estimated that 12 million people are currently infected and around 2 million infections occur each year. current treatments suffer of high toxicity for the patient, low efficacy toward the parasite, high cost, and are losing effectiveness due to parasite resistance. discovering novel small molecule with high specificity/selectivity and drug-like properties for anti-leishmanial activity remains a significant ...201526410073
the role of the c-terminus and kpn loop in the quaternary structure stability of nucleoside diphosphate kinase from leishmania parasites.nucleoside diphosphate kinase (ndk) is a housekeeping enzyme that plays key roles in nucleotide recycling and homeostasis in trypanosomatids. moreover, it is secreted by the intracellular parasite leishmania to modulate the host response. these functions make ndk an attractive target for drug design and for studies aiming at a better understanding of the mechanisms mediating host-pathogen interactions. here, we report the crystal structures of three mutants of the ndk from leishmania major (lmnd ...201526410384
bismuth(iii) α-hydroxy carboxylates: highly selective toxicity of glycolates towards leishmania major.eight bismuth(iii) complexes derived from the simple α-hydroxycarboxylic acids; gluconic (h₆-glu), tartaric (h₄-tar), mandelic (h₂-man), malic (h₃-mal) and glycolic (h₂-gly) have been synthesised and characterised. the complexes are formed through direct treatment of the organic acids with bi(no₃)3·5h₂o ([bi(h₂-tar)(h₃- tar)] 2, [bi(mal)(no₃)(h₂o)₂] 6, [bi(gly)(no₃)(h₂o)] 8) or bi(otbu)₃ ([bi(h-tar)(h₂o)₂] 1, [bi(man)(h-man) (h₂o)] 4, [bi2(h-mal)₃] 5, [bi(gly)(h-gly)] 7), or through metathesis o ...201526411702
magnesium oxide nanoparticles coated with glucose can silence important genes of leishmania major at sub-toxic concentrations.the aim of this study was to investigate the effect of magnesium oxide nanoparticles (mgo nps) and mgo nps coated with glucose (monpcg) on leishmania (l) major. first, the promastigotes of l. major were separately incubated with serial concentrations of mgo nps and monpcg for 24, 48, and 72 h at 37 °c. then, the cell viability of promastigotes was evaluated by mtt assay. on the other hand, the relative expression of cpb and gp63 genes was detected by quantitative-real time pcr. based on results, ...201526413865
stability and toxicity of tris-tolyl bismuth(v) dicarboxylates and their biological activity towards leishmania major.a series of 29 tris-tolyl bismuth(v) di-carboxylato complexes of composition [bi(tol)3(o2cr)2] involving either ortho, meta or para substituted tolyl ligands have been synthesized and characterised. of these 15 were assessed for their toxicity towards leishmania promastigotes and human fibroblast cells, with ten then being subsequently assessed against parasite amastigotes. the carboxylate ligands are drawn from a series of substituted and biologically relevant benzoic acids which allow a compar ...201526425978
pathogen- and host-directed antileishmanial effects mediated by polyhexanide (phmb).cutaneous leishmaniasis (cl) is a neglected tropical disease caused by protozoan parasites of the genus leishmania. cl causes enormous suffering in many countries worldwide. there is no licensed vaccine against cl, and the chemotherapy options show limited efficacy and high toxicity. localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/ ...201526431058
leishmania major phosphoglycerate kinase transcript and protein stability contributes to differences in isoform expression levels.leishmania contains two phosphoglycerate kinase (pgk) genes, pgkb and pgkc, which code for the cytosolic and glycosomal isoforms of the enzyme, respectively. although differences in pgkb and pgkc transcript and protein levels and isoform activities have been well documented, the mechanisms of control of both transcript and protein abundance have not been described to date. to better understand the regulation of leishmania pgk expression, we investigated the stabilities of both pgk transcripts us ...201526431819
cd98 heavy chain is a potent positive regulator of cd4+ t cell proliferation and interferon-γ production in vivo.upon their recognition of antigens presented by the mhc, t cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. the cd98 heavy chain (cd98hc, slc3a2) plays a crucial role in the proliferation of both cd4+ and cd8+ t cells, although it is unclear if cd98hc directly regulates the t cell effector functions that are not linked with t cell proliferation in vivo. here, we demonstrate that cd98hc is requi ...201526444422
mast cells have no impact on cutaneous leishmaniasis severity and related th2 differentiation in resistant and susceptible mice.the genus leishmania comprises different protozoan parasites which are causative agents of muco-cutaneous and systemic, potentially lethal diseases. after infection with the species leishmania major, resistant mice expand th1 cells which stimulate macrophages for leishmania destruction. in contrast, susceptible mice generate th2 cells which deactivate macrophages, leading to systemic spread of the pathogens. th-cell differentiation is determined within the first days, and th2 cell differentiatio ...201626449668
cutaneous leishmaniasis in the central provinces of hama and edlib in syria: vector identification and parasite typing.cutaneous leishmaniasis is a disease transmitted by sand fly bites. this disease is highly prevalent in syria where leishmania major and leishmania tropica are the known aetiological agents. in 2011, more than 58,000 cases were reported in the country by the ministry of health. the central region of the country harbors 20 % of the reported cases. however, the epidemiology of the disease in this area is not well understood. an epidemiological survey was conducted in 2010 to identity the circulati ...201526459055
[gerbils, as experimental animals (meriones unguiculatus): is a good role model for leishmania major?].this study aimed to observation the possible visceralization tendency and dissemination of l. major amastigotes in gerbils (meriones unguiculatus) using a classic smear technique, inoculated into enriched novy-macneal-nicolle (nnn) culture and polymerase chain reaction (pcr) assay for diagnosis of infection.201526470928
some epidemiological aspects of cutaneous leishmaniasis in a new focus, central iran.following the epidemic of cutaneous leishmaniasis in khatam county, yazd province, this study was carried out to determine vector, and animal reservoir host(s) and investigate the human infection during 2005-2006. four rural districts where the disease had higher prevalence were selected. sticky paper traps were used to collect sand flies during april to november, biweekly. meanwhile rodents were captured using sherman traps from august to november. households and primary schools were visited an ...201526483838
the immunology of a healing response in cutaneous leishmaniasis treated with localized heat or systemic antimonial therapy.the effectiveness of systemic antimonial (sodium stibogluconate, pentostam, ssg) treatment versus local heat therapy (thermomed) for cutaneous leishmaniasis was studied previously and showed similar healing rates. we hypothesized that different curative immune responses might develop with systemic and local treatment modalities.201526485398
implication of different domains of the leishmania major metacaspase in cell death and autophagy.metacaspases (mcas) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine-cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. the role of mcas is subject to debate: roles in cell cycle control, in cell death or even in cell survival have been suggested. in this study, using a leishmania major mca-deficient strain, we showed that l. major mca (lmjmca) not only had a role similar to caspases in cell death but a ...201526492367
antileishmanial activity of compounds derived from the medicines for malaria venture open access box against intracellular leishmania major amastigotes.leishmaniasis is a complex tropical disease caused by kinetoplastid parasitic protozoa of the genus leishmania and is transmitted by the sand fly insect vector. cutaneous leishmaniasis (cl) is the most common form of this disease, and cl infections often result in serious skin lesions and scars. cl remains a public health problem in many endemic countries worldwide because of the absence of effective, safe, and cost-effective drugs for treatment. one of the strategies we chose to use to find nov ...201626503273
specific k39 antibody response and its persistence after treatment in patients with imported leishmaniasis.the sensitivity of a k39 elisa (leishmania igg, virion/serion) for the detection of antibodies in patients with imported leishmaniasis was compared with an immunofluorescence assay (ifa), which was applied as "golden standard". the retrospective study comprised 93 ifa-positive or borderline sera from 42 patients with visceral (n = 16) or cutaneous (n = 26) leishmaniasis. patients had acquired infection predominately in the mediterranean area or the middle east. the leishmania species (leishmania ...201626508007
nlrp12 is a neutrophil-specific, negative regulator of in vitro cell migration but does not modulate lps- or infection-induced nf-κb or erk signalling.nod-like receptors (nlr) are a family of cytosolic pattern recognition receptors that include many key drivers of innate immune responses. nlrp12 is an emerging member of the nlr family that is closely related to the well-known inflammasome scaffold, nlrp3. since its discovery, various functions have been proposed for nlrp12, including the positive regulation of dendritic cell (dc) and neutrophil migration and the inhibition of nf-κb and erk signalling in dc and macrophages. we show here that nl ...201626514298
immunotherapeutic effects of chitin in comparison with chitosan against leishmania major infection.chitin and chitosan microparticles (mps) are important immune system stimulators. the aim of this study was to evaluate the protective effects of these compounds in comparison with each other against leishmania infection in balb/c mice infected with leishmania major (l. major). female balb/c mice were injected subcutaneously with 2×10(5) promastigotes. chitin and/or chitosan mps (<40 μm) were subcutaneously injected in the balb/c mice with two-day intervals until two weeks. mice in all groups we ...201626518128
the activity of ozonated olive oil against leishmania major promastigotes.cutaneous leishmaniasis is a common and endemic disease in khorasan province in north-east of iran. the pentavalant antimony (sb v) is the mainstay of treatment that has many side effects and resistance to the drug has been reported. the microbicidal effect of ozone was proven in different microorganisms. since there is no study in this respect and to achieve a low cost and effective treatment, we decided to evaluate the efficacy of ozone against promastigotes of leishmania major, in vitro.201526523224
depletion of udp-glucose and udp-galactose using a degron system leads to growth cessation of leishmania major.interconversion of udp-glucose (udp-glc) and udp-galactose (udp-gal) by the udp-glc 4´-epimerase intimately connects the biosynthesis of these two nucleotide sugars. their de novo biosynthesis involves transformation of glucose-6-phosphate into glucose-1-phosphate by the phosphoglucomutase and subsequent activation into udp-glc by the specific udp-glc pyrophosphorylase (ugp). besides ugp, leishmania parasites express an uncommon udp-sugar pyrophosphorylase (usp) able to activate both galactose-1 ...201526529232
first detection of leishmania major dna in sergentomyia (sintonius) clydei (sinton, 1928, psychodidae: phlebotominae), from an outbreak area of cutaneous leishmaniasis in tunisia.in recent years there has been growing interest in sergentomyia species. their role in the spread of mammalian leishmaniasis appears repeatedly in the literature and the possibility of its implication in leishmania transmission to humans remains controversial. sergentomyia (sintonius) clydei is one of several cryptic species sharing therefore common morphologic criteria with others species of the subgenera sintonius. little is known about this specie in tunisia. we sampled and identified differe ...201626538476
genetic differences between two leishmania major-like strains revealed by suppression subtractive hybridization.leishmania major, the causative agent of zoonotic leishmaniasis, is restricted to old world countries. molecular and biochemical techniques have been used to identify some l. major-like isolated in south america including brazil. here, two l. major-like strains, one virulent (bh49) and one non-virulent (bh121), were subjected to suppression subtractive hybridization (ssh) technique in order to identify differentially expressed genes. ssh technique identified nine cdna fragments exhibiting high h ...201526542948
biophysical characterization of the nucleoside diphosphate kinase of leishmania major and effect of the p95s mutation.nucleoside diphosphate kinases (ndk; ec 2.7.4.6) are enzymes required for maintaining intracellular levels of nucleosides triphosphates (ntp) through transfer the γ-phosphoryl group from a ntp to a ndp. the enzyme is associated with several biological functions including prevention of host atp-mediated cytolysis during pathogenic infections. here we present the biophysical characterization of ndk from leishmania major and the effect of a mutation on the protein structure in solution. the structu ...201626548994
cinnamic acid bornyl ester derivatives from valeriana wallichii exhibit antileishmanial in vivo activity in leishmania major-infected balb/c mice.human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by leishmania major or leishmania donovani, respectively. some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileish ...201526554591
the role of glcnac-pi-de-n-acetylase gene by gene knockout through homologous recombination and its consequences on survival, growth and infectivity of leishmania major in in vitro and in vivo conditions.at present, there are no efficacious vaccines or effective drugs against leishmaniasis; therefore new and innovative control methods are urgently required. one way to achieve this important goal is through using reverse genetic engineering to evaluate important enzymes, proteins and macromolecules. one of the most important enzymes for glycosylphosphatidylinositol (gpi) biosynthetic pathways is glcnac-pi-de-n-acetylase (gpi12). the molecular constructs were cloned in escherichia coli strain top ...201626571069
morphological and immunohistochemical clues for the diagnosis of cutaneous leishmaniasis and the interpretation of cd1a status.cd1a immunoexpression by amastigotes of leishmania major and l tropica has been demonstrated.201626577511
the changing profile of cutaneous leishmaniasis agent in a central province of iran.cutaneous leishmaniasis in iran is usually caused by leishmania major or l. tropica. however, the direct examination or the cultures of biopsies for diagnosis are not very sensitive. the objective of this study was to identify the responsible species obtained from patients suspected of cutaneous leishmaniasis referred to the reference laboratory atyazd in iran during 2010-2011 using parasitological and molecular assays. after completing a clinical/epidemiologic data questionnaire for 145 patient ...201326591671
metabolomics-based study of logarithmic and stationary phases of promastigotes in leishmania major by 1h nmr spectroscopy.cutaneous leishmaniasis is one of the most important parasitic diseases in humans. in this disease, one of the responsible organisms is leishmania major, which is transmitted by sandfly vector. there are specific differences in biochemical profiles and metabolite pathways in logarithmic and stationary phases of leishmania parasites. in the present study, 1h nmr spectroscopy was used to examine the metabolites outliers in the logarithmic and stationary phases of promastigotes in l. major to enlig ...201626592771
development of a new antileishmanial aziridine-2,3-dicarboxylate-based inhibitor with high selectivity for parasite cysteine proteases.leishmaniasis is one of the major neglected tropical diseases of the world. druggable targets are the parasite cysteine proteases (cps) of clan ca, family c1 (cac1). in previous studies, we identified two peptidomimetic compounds, the aziridine-2,3-dicarboxylate compounds 13b and 13e, in a series of inhibitors of the cathepsin l (cl) subfamily of the papain clan cac1. both displayed antileishmanial activity in vitro while not showing cytotoxicity against host cells. in further investigations, th ...201626596939
"bind and crawl" association mechanism of leishmania major peroxidase and cytochrome c revealed by brownian and molecular dynamics simulations.leishmania major, the parasitic causative agent of leishmaniasis, produces a heme peroxidase (lmp), which catalyzes the peroxidation of mitochondrial cytochrome c (lmcytc) for protection from reactive oxygen species produced by the host. the association of lmp and lmcytc, which is known from kinetics measurements to be very fast (∼10(8) m(-1) s(-1)), does not involve major conformational changes and has been suggested to be dominated by electrostatic interactions. we used brownian dynamics simul ...201526598276
new primers for detection of leishmania infantum using polymerase chain reaction.leishmania infantum causes visceral leishmaniasis (vl) in the new world. the diagnosis of vl is confirmed by parasitological and serological tests, which are not always sensitive or specific. our aim was to design new primers to perform a polymerase chain reaction (pcr) for detecting l. infantum. sequences of the minicircle kinetoplast dna (kdna) were obtained from genbank, and the flc2/rlc2 primers were designed. samples of dna from l. infantum, leishmania amazonensis, leishmania braziliensis, ...201726603223
crystal structure of phosphoglucomutase from leishmania major at 3.5 å resolution.the crystal structure of phosphoglucomutase (lmpgm) from the parasite leishmania major has been solved at 3.5 å resolution. although the active form of the enzyme is monomeric in solution, four molecules (a, b, c, d) were found in the asymmetric unit, of which the pairs (a,d) and (b,c) were of identical inter-subunit geometry. the parasitic enzyme constituted of four domains exhibited the canonical 'heart' shape of the protein, with domains i to iii having a conserved α|β core, while the fourth ...201626607241
natural hybrid of leishmania infantum/l. donovani: development in phlebotomus tobbi, p. perniciosus and lutzomyia longipalpis and comparison with non-hybrid strains differing in tissue tropism.infection caused by parasites from l. donovani complex can manifest as a serious visceral disease or a self-healing milder cutaneous form. the different tropism and pathology in humans is caused by the interaction between parasites, host and vector determinants but the mechanisms are not well understood. in cukurova region in turkey we previously identified a major focus of cutaneous leishmaniasis caused by l. donovani/infantum hybrids (cuk strain) and isolated this parasite from the locally abu ...201526608249
antileishmanial diterpenoid alkaloids from aconitum spicatum (bruhl) stapf.the crude extracts of tubers of aconitum spicatum (bruhl) stapf were investigated for in vitro antileishmanial activity against leishmania major. the dichloromethane extract at ph 2.5 showed antileishmanial activity with ic50 value of 27.10 ± 0.0 μg/ml. chromatographic purification of the dichloromethane extract led to isolation of three c-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). compounds 3 and 2 showed antileishmanial activity with ic50 = 36.10 ± 3 ...201526615865
4-arylamino-6-nitroquinazolines: synthesis and their activities against neglected disease leishmaniasis.4-arylamino-6-nitroquinazolines (2-25) were synthesized and evaluated for their leishmanicidal activities against leishmania major promastigotes in vitro with ic50 values = 1.87-61.48 μm. among the twenty four synthetic derivatives, 4-[4'-(methylsulfanyl)phenyl]amino-6-nitroquinazoline (21), and 4-(2'-methoxyphenyl)amino-6-nitroquinazoline (8) showed excellent antileishmanial activities with ic50 values 1.87 ± 0.31 and 4.37 ± 0.02 μm, respectively, more active than the standard drug, pentamidine ...201626619389
double-blind randomized efficacy field trial of alum precipitated autoclaved leishmania major (alum-alm) vaccine mixed with bcg plus imiquimod vs. placebo control group.canine visceral leishmaniasis (cvl) is not only an emerging veterinary concern but also a public health threat in endemic areas. the aim of this study was to assess the efficacy, immunogenicity and safety of two doses of aluminum hydroxide (alum) precipitated leishmania major (alum-alm) mixed with bcg plus imiquimod against cvl.201726622290
differential impact of lpg-and pg-deficient leishmania major mutants on the immune response of human dendritic cells.leishmania major infection induces robust interleukin-12 (il12) production in human dendritic cells (hdc), ultimately resulting in th1-mediated immunity and clinical resolution. the surface of leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (lpg) and other phosphoglycan-containing molecules (pgs), making these glycoconjugates the likely pathogen-associated molecular patterns (pamps) responsible for il12 induction.201526630499
comparative study of viscerotropic pathogenicity of leishmania major amastigotes and promastigotes based on identification of mitochondrial and nucleus sequences.experimental viscerotropic leishmaniasis is regularly caused by leishmania tropica promastigotes. in the current investigation, the viscerotropic pathogenicities of leishmania major amastigotes and promastigotes were compared and evaluated based on their heterogeneity traits and number of inoculated parasites in experimental mammalian hosts. serous exudate from 50 patients was infected, 44 with l. major and 6 with l. tropica; only balb/c mice inoculated with 1-2 × 10(4-6) l. major amastigotes ma ...201626631188
hisak70: progress towards a vaccine against different forms of leishmaniosis.leishmania major and leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (cl) and visceral leishmaniosis (vl), respectively. the leishmanioses represent the second-largest parasitic killer in the world after malaria. recently, we succeeded in generating a plasmid dna (pcmv-hisa70m2a) and demonstrated that immunized mice were protected against l. major challenge. the efficacy of the dna-vaccine was further enhanced by the inclusion of kmp-11 antigen int ...201526653170
the mechanistic study of leishmania major dihydro-orotate dehydrogenase based on steady- and pre-steady-state kinetic analysis.leishmania major dihydro-orotate dehydrogenase (dhodhlm) has been considered as a potential therapeutic target against leishmaniasis. dhodhlm, a member of class 1a dhodh, oxidizes dihydro-orotate (dho) to orotate (oro) during pyrimidine biosynthesis using fumarate (fum) as the oxidizing substrate. in the present study, the chemistry of reduction and reoxidation of the flavin mononucleotide (fmn) cofactor in dhodhlm was examined by steady- and pre-steady state kinetics under both aerobic and anae ...201626656485
apoptotic cell clearance of leishmania major-infected neutrophils by dendritic cells inhibits cd8⁺ t-cell priming in vitro by mer tyrosine kinase-dependent signaling.neutrophils are the predominant recruited and infected cells during the early stages of leishmania major infection in the skin, and depletion of neutrophils promotes immunity to infection transmitted by sand fly bite. in order to better understand how the acute neutrophilic response suppresses immunity, we assessed the consequences of the interaction between neutrophils recovered from the skin-inoculation site and bone marrow-derived dendritic cells (dcs) in vitro. the capture of infected, apopt ...201526658192
cloning and constructing a plasmid encoding leishmania eukaryotic initiation factor gene of leishmania major fused with green fluorescent protein gene as a vaccine candidate.leishmaniasis is usually treated with chemotherapy; however, toxicity, resistance and high-cost limit use of the chemical drugs. leishmania eukaryotic initiation factor (leif) protein acts the same as interleukin (il)-12 and reduces the secretion of il-4 in lymph node cells of mice infected with leishmania major. the aim of this study was cloning of the gene encoding leif antigen into eukaryotic expression plasmid pegfp-n1.201526681377
genome-wide prediction of vaccine candidates for leishmania major: an integrated approach.despite the wealth of information regarding genetics of the causative parasite and experimental immunology of the cutaneous leishmaniasis, there is currently no licensed vaccine against it. in the current study, a two-level data mining strategy was employed, to screen the leishmania major genome for promising vaccine candidates. first, we screened a set of 25 potential antigens from 8312 protein coding sequences, based on presence of signal peptides, gpi anchors, and consensus antigenicity predi ...201526681959
egfp reporter protein: its immunogenicity in leishmania-infected balb/c mice.optical reporter genes such as green fluorescent protein (gfp) and luciferase are efficiently and widely used in monitoring and studying the protective/therapeutic potential of candidate agents in leishmaniasis. but several observations and controversial reports have generated a main concern, whether enhanced gfp (egfp) affects immune response. to address this issue, we studied the immunogenicity of egfp in vivo by two lines of stably transfected parasites (leishmania major (egfp) or l. major (e ...201626685673
the nlrp3 inflammasome, il-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of leishmania major in c57bl/6 mice.infection of c57bl/6 mice with most leishmania major strains results in a healing lesion and clearance of parasites from the skin. infection of c57bl/6 mice with the l. major seidman strain (lmsd), isolated from a patient with chronic lesions, despite eliciting a strong th1 response, results in a nonhealing lesion, poor parasite clearance, and complete destruction of the ear dermis. we show here that in comparison to a healing strain, lmsd elicited early upregulation of il-1β mrna and il-1β-prod ...201626689285
first report of naturally infected sergentomyia minuta with leishmania major in tunisia.many sand fly species are implicated in the transmission cycle of leishmania parasites around the world. incriminating new sand flies species, as vectors of leishmania is crucial to understanding the parasite-vector transmission cycle in different areas in tunisia and surrounding countries.201526692017
expression of pd-1/lag-3 and cytokine production by cd4(+) t cells during infection with plasmodium parasites.cd4(+) t cells play critical roles in protection against the blood stage of malarial infection; however, their uncontrolled activation can be harmful to the host. in this study, in which rodent models of plasmodium parasites were used, the expression of inhibitory receptors on activated cd4(+) t cells and their cytokine production was compared with their expression in a bacterial and another protozoan infection. cd4(+) t cells from mice infected with p. yoelii 17xl, p yoelii 17xnl, p. chabaudi, ...201626696540
mesenchymal stem cells alter macrophage immune responses to leishmania major infection in both susceptible and resistance mice.mesenchymal stem cells (mscs) are attracted to inflammation site and switch immune system to modulate inflammatory responses. this ability makes mscs the best candidate cells for stem cell therapy of infection diseases. therefore, we aimed to evaluate the modulatory effect of adipose-derived mscs (ad-mscs) on macrophages in leishmania (l.) major infection. macrophages and mscs were isolated from both susceptible (balb/c) and resistance (c57bl/6) strains. after co-culture of ad-mscs with macropha ...201626703818
inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on leishmania major growth and trypanosoma brucei trypanothione reductase.a number of phenothiazine-, phenoxazine- and related tricyclics-derived chloroacetamides were synthesized and evaluated in vitro for antiprotozoal activities against leishmania major (l. major) promastigotes. several analogs were remarkably potent inhibitors, with antileishmanial activities being comparable or superior to those of the reference antiprotozoal drugs. furthermore, we explored the structure-activity relationships of n-10 haloacetamides that influence the potency of such analogs towa ...201626708110
cationic immune stimulating complexes containing soluble leishmania antigens: preparation, characterization and in vivo immune response evaluation.cationic immune stimulating complexes (pluscoms) are particulate antigen delivery systems. pluscoms consist of cationic immunostimulatory complexes (iscoms) derivatives and are able to elicit in vivo t cell responses against an antigen.201526714419
simultaneous transcriptional profiling of leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions.parasites of the genus leishmania are the causative agents of leishmaniasis, a group of diseases that range in manifestations from skin lesions to fatal visceral disease. the life cycle of leishmania parasites is split between its insect vector and its mammalian host, where it resides primarily inside of macrophages. once intracellular, leishmania parasites must evade or deactivate the host's innate and adaptive immune responses in order to survive and replicate.201526715493
conserved curvature of rna polymerase i core promoter beyond rrna genes: the case of the tritryps.in trypanosomatids, the rna polymerase i (rnapi)-dependent promoters controlling the ribosomal rna (rrna) genes have been well identified. although the rnapi transcription machinery recognizes the dna conformation instead of the dna sequence of promoters, no conformational study has been reported for these promoters. here we present the in silico analysis of the intrinsic dna curvature of the rrna gene core promoters in trypanosoma brucei, trypanosoma cruzi, and leishmania major. we found that, ...201526718450
lmabcb3, an atypical mitochondrial abc transporter essential for leishmania major virulence, acts in heme and cytosolic iron/sulfur clusters biogenesis.mitochondria play essential biological functions including the synthesis and trafficking of porphyrins and iron/sulfur clusters (isc), processes that in mammals involve the mitochondrial atp-binding cassette (abc) transporters abcb6 and abcb7, respectively. the mitochondrion of pathogenic protozoan parasites such as leishmania is a promising goal for new therapeutic approaches. leishmania infects human macrophages producing the neglected tropical disease known as leishmaniasis. like most trypano ...201626728034
the dynamics of lateral gene transfer in genus leishmania - a route for adaptation and species diversification.the genome of leishmania major harbours a comparably high proportion of genes of prokaryote origin, acquired by lateral gene transfer (lgt). some of these are present in closely related trypanosomatids, while some are detected in leishmania only. we have evaluated the impact and destiny of lgt in genus leishmania.201626730948
correction: depletion of udp-glucose and udp-galactose using a degron system leads to growth cessation of leishmania major.[this corrects the article doi: 10.1371/journal.pntd.0004205.].201626735928
antileishmanial activities of greek juniper (juniperus excelsa m.bieb.) against leishmania major promastigotes.petroleum ether, chloroform, ethyl acetate, and n-butanol fractions of greek juniper (juniperus excelsa m.bieb. from the family cupressaceae) were evaluated for antileishmanial activities against leishmania major promastigotes compared to meglumine antimoniate (glucantime). in vitro toxicity assay was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and microplate elisa reader. extracts were prepared in ethanol/dimethyl sulfoxide (80/20) at 10 to 0.62 mg/ml. the stan ...201726747836
killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.protozoan infections are a serious global health problem. natural killer (nk) cells and cytolytic t lymphocytes (ctls) eliminate pathogen-infected cells by releasing cytolytic granule contents--granzyme (gzm) proteases and the pore-forming perforin (pfn)--into the infected cell. however, these cytotoxic molecules do not kill intracellular parasites. cd8(+) ctls protect against parasite infections in mice primarily by secreting interferon (ifn)-γ. however, human, but not rodent, cytotoxic granule ...201626752517
cross-protective efficacy from a immunogen firstly identified in leishmania infantum against tegumentary leishmaniasis.experimental vaccine candidates have been evaluated to prevent leishmaniasis, but no commercial vaccine has been proved to be effective against more than one parasite species. lihyt is a leishmania-specific protein that was firstly identified as protective against leishmania infantum. in this study, lihyt was evaluated as a vaccine to against two leishmania species causing tegumentary leishmaniasis (tl): leishmania major and leishmania braziliensis. balb/c mice were immunized with rlihyt plus sa ...201626756314
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