Publications

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rna interference mediated knockdown of brugia malayi udp-galactopyranose mutase severely affects parasite viability, embryogenesis and in vivo development of infective larvae.galactofuranose is an essential cell surface component present in bacteria, fungi and several nematodes such as caenorhabditis spp., brugia spp., onchocerca spp. and strongyloides spp. this sugar maintains the integrity of parasite surface and is essential for virulence. udp-galactopyranose mutase (bmugm) plays a key role in galf biosynthesis by catalyzing conversion of udp-galactopyranose into udp-galactofuranose and knockout studies of the gene in leishmania major, mycobacterium and aspergillu ...201728103957
canine leishmaniosis caused by leishmania major and leishmania tropica: comparative findings and serology.infection and clinical disease associated with leishmania major and leishmania tropica, two common agents of human cutaneous leishmaniosis, have rarely been reported in dogs. this study describes dogs infected with these leishmania spp. prevalent in the middle east and north africa, and compares the serological response of dogs infected with leishmania infantum, l. major or l. tropica to whole promastigote antigen enzyme-linked immunosorbent assay (elisa) of each species and to rk39 dipstick.201728285601
understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional ts-dhfr.most species, such as humans, have monofunctional forms of thymidylate synthase (ts) and dihydrofolate reductase (dhfr) that are key folate metabolism enzymes making critical folate components required for dna synthesis. in contrast, several parasitic protozoa, including leishmania majorg(lm), plasmodium falciparum (pf), toxoplasma gondii (tg) and cryptosporidium hominis(ch), contain a unique bifunctional thymidylate synthase-dihydrofolate reductase (ts-dhfr) having the two sequential catalytic ...201728338744
designing and cloning molecular constructs to knock out n-acetylglucosamine phosphatidylinositol de-n-acetylase (gpi12) gene in leishmania major (mrho/ir/75/er).leishmaniasis represents a major public health concern in tropical and sub-tropical countries. at present, there is no efficacious vaccine against the disease and new control methods are needed. one way to access this important goal is to knock out genes of specific macromolecules to evaluate the effect of deletion on the growth, multiplication, pathogenesis and immunity of the parasite. the aim of this study was to design and clone molecular constructs to knock out n-acetylglucosamine phosphati ...201728127356
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
genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite leishmania.5-hydroxymethyluracil (5hmu) is a thymine base modification found in the genomes of a diverse range of organisms. to explore the functional importance of 5hmu, we develop a method for the genome-wide mapping of 5hmu-modified loci based on a chemical tagging strategy for the hydroxymethyl group.201728137275
pharmacological inhibition of p110δ subunit of pi3k confers protection against experimental leishmaniasis.this study aimed to evaluate the immuno-prophylactic and -therapeutic effect of p110δ-specific pharmacological inhibitors (cal-101 and ic87114), either alone or in combination with amphotericin b, against experimental cutaneous leishmaniasis (cl) and visceral leishmaniasis (vl).201727999013
synthesis and in vitro screening of 29, 30-dibromo-28-oxoallobetulin against parasitic protozoans, leishmania donovani and leishmania major.a simple synthesis and in vitro antileishmanial activity of 29,30-dibromo-28-oxoallobetulin against the parasitic protozoans, leishmania donovani and leishmania major is described. the structure of the compound is established on the basis of spectral data (ir, nmr, ms). both the antiproliferative effect and the cell cycle progression were studied.201726009654
psychosocial impact of scars due to cutaneous leishmaniasis on high school students in errachidia province, morocco.in morocco, cutaneous leishmaniasis (cl) is usually known to be a slowly healing localized skin disease, but in some cases, it can lead to mutilating scars. the outbreak of cl due to leishmania major in the errachidia province in southeastern morocco between 2008 and 2010 left many adolescents with permanent scar tissue on the face or other exposed body parts. we studied the psychosocial impact of cl on these young people.201728385151
the transcriptome of leishmania major developmental stages in their natural sand fly vector.the life cycle of the leishmania parasite in the sand fly vector involves differentiation into several distinctive forms, each thought to represent an adaptation to specific microenvironments in the midgut of the fly. based on transcriptome sequencing (rna-seq) results, we describe the first high-resolution analysis of the transcriptome dynamics of four distinct stages of leishmania major as they develop in a natural vector, phlebotomus duboscqi the early transformation from tissue amastigotes t ...201728377524
treatment outcome of the drug-resistant zoonotic cutaneous leishmaniasis by glucantime.resistance of leishmania species to antimonial drugs has increased. hence, in the present study leishmania major isolates were collected from patients with resistance phenotype and the presence/absence of resistance to glucantime was investigated.201728349020
antiparasitic lead discovery: toward optimization of a chemotype with activity against multiple protozoan parasites.human african trypanosomiasis (hat), chagas disease, and leishmaniasis present a significant burden across the developing world. existing therapeutics for these protozoal neglected tropical diseases suffer from severe side effects and toxicity. previously, neu-1045 (3) was identified as a promising lead with cross-pathogen activity, though it possessed poor physicochemical properties. we have designed a library of analogues with improved calculated physicochemical properties built on the quinoli ...201728337329
lb broth-lyophilized rabbit serum (llr) as a new and suitable culture medium for cultivation of promastigotes of leishmania major.fetal calf serum is the major part and the most expensive ingredient of the leishmania culture media. here, the efficacy of the lb broth-lyophilized rabbit serum medium (llr) was evaluated in cultivation of leishmaniamajor. conventional luria-bertani (lb) broth medium was prepared and autoclaved for 15 min at 121 °c and then lyophilized rabbit serum was added at the 1, 2.5, 5 and 10 % final concentrations. the efficacy of medium was evaluated by assessing the growth ability and replication patte ...201728316420
clinical presentation of cutaneous leishmaniasis caused by leishmania major.the diagnosis of cutaneous leishmaniasis (cl) is based on the microscopic detection of amastigote, isolation of the parasite, or the detection of leishmania dna. nevertheless, since these techniques are time consuming and not usually available in many endemic countries, the diagnosis remains clinical. consequently, such disease may be overlooked because of its similarity to other skin diseases. the aim of this study is to describe the clinical polymorphism of cl caused by leishmaniamajor.201728253508
effect of hydroalcoholic extract of echinacea purpurea in combination with meglumine antimoniate on treatment of leishmania major-induced cutaneous leishmaniasis in balb/c mice.progressive resistance of leishmania parasite to available drugs including, meglumine antimoniate, has been reported from various regions of the world, especially iran.201728251109
biotransformation of a potent anabolic steroid, mibolerone, with cunninghamella blakesleeana, c. echinulata, and macrophomina phaseolina, and biological activity evaluation of its metabolites.seven metabolites were obtained from the microbial transformation of anabolic-androgenic steroid mibolerone (1) with cunninghamella blakesleeana, c. echinulata, and macrophomina phaseolina. their structures were determined as 10β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (2), 6β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (3), 6β,10β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (4), 11β,17β-dihydroxy-(20-hydroxymethyl)-7α,17α-dimethylestr-4-en-3-one (5), 1α,17β-dihydroxy-7α,17α-dimethylestr ...201728234904
immunogenicity and efficacy of a bivalent dna vaccine containing leif and tsa genes against murine cutaneous leishmaniasis.there is no effective vaccine for the prevention and elimination of leishmaniasis. for this reason, we assessed the protective effects of dna vaccines containing leif, tsa genes alone, or leif-tsa fusion against cutaneous leishmaniasis pegfp-n1 plasmid (empty vector) and phosphate buffer saline (pbs) were used as control groups. therefore, cellular and humoral immune responses were evaluated before and after the challenge with leishmania major. lesion diameter was also measured 3-12 weeks after ...201728233451
circulating species of leishmania at microclimate area of boulemane province, morocco: impact of environmental and human factors.cutaneous leishmaniasis (cl) is widely distributed in morocco where its geographical range and incidence are related to environmental factors. this study aimed to examine the impact of several factors on the distribution of cl in boulemane province, which is characterized by several microclimates, and to identify the leishmania species circulating in these areas.201728228154
unusual presentation of cutaneous leishmaniasis: ocular leishmaniasis.the leishmaniases are parasitic diseases that are transmitted to humans by infected female sandflies. cutaneous leishmaniasis (cl) is one of 3 main forms of the disease. cl is the most common form of the disease and is endemic in many urban and rural parts of iran and usually caused by two species of leishmania: l. major and l. tropica. we report a case of unusual leishmaniasis with 25 lesions on exposed parts of the body and right eyelid involvement (ocular leishmaniasis). the patient was a 75- ...201728210511
enhanced survival of leishmania major in neutrophil granulocytes in the presence of apoptotic cells.neutrophil granulocytes are the first leukocytes that encounter and phagocytose leishmania major (l. major) parasites in the infected skin. the parasites can nonetheless survive within neutrophils. however, the mechanisms enabling the survival of leishmania within neutrophils are still elusive. previous findings indicated that human neutrophils can engulf apoptotic cells. since apoptotic neutrophils are abundant in infected tissues, we hypothesized that the uptake of apoptotic cells results in d ...201728187163
pretreatment of mesenchymal stem cells with leishmania major soluble antigens induce anti-inflammatory properties in mouse peritoneal macrophages.recent studies have demonstrated the influential role of microbial stimulus in characteristics and immunomodulatory effects of mesenchymal stem cells (mscs). due to the migration of mscs to infection site, it is of importance to understand the interaction of microbial ligands with mscs in order to clarify the positive or negative role of mscs in the control of infection. in this research, we assess leishmanial soluble antigen (lsa)-primed mscs on macrophage immune responses to lipopolysaccharide ...201728176354
progressive perforation of the nasal septum due to leishmania major: a case of mucosal leishmaniasis in a traveler.this report describes a case of mucosal leishmaniasis caused by leishmania major with destructive perforation of the nasal septum illustrating the diagnostic challenges of a rare clinical presentation of l. major infection in a traveler. the atypical presentation may have been associated with the use of cortisone as a potential trigger for the progressive destruction of the nasal septum.201728138053
use of optical imaging technology in the validation of a new, rapid, cost-effective drug screen as part of a tiered in vivo screening paradigm for development of drugs to treat cutaneous leishmaniasis.in any drug discovery and development effort, a reduction in the time of the lead optimization cycle is critical to decrease the time to license and reduce costs. in addition, ethical guidelines call for the more ethical use of animals to minimize the number of animals used and decrease their suffering. therefore, any effort to develop drugs to treat cutaneous leishmaniasis requires multiple tiers of in vivo testing that start with higher-throughput efficacy assessments and progress to lower-thr ...201728137819
dataset for distribution of sider2 elements in the leishmania major genome and transcriptome.this paper contains data related to the research article entitled "genomic cartography and proposal of nomenclature for the repeated, interspersed elements of the leishmania major sider2 family and identification of sider2-containing transcripts" [1]. sider2 elements are repeated sequences, derived from, nowadays, extinct retrotransposons, that populate the genomes of protist of the genera leishmania. this dataset (supplementary file 1), an inventory of 1100 sider2 elements, was generated by sur ...201728127581
expression of pro-inflammatory genes in lesions and neutrophils during leishmania major infection in balb/c mice.leishmaniasis is a worldwide disease prevalent in tropical and sub-tropical countries in the world. characterization of inflammatory responses produced in cutaneous leishmaniasis has not yet been completed.201728127365
holothuria leucospilota extract induces apoptosis in leishmania major promastigotes.the present study aimed to survey antileishmanial activity of methanolic holothuria leucospilota extract against leishmania major promastigotes in vitro.201728127339
optimization of the timing of induction for the assessment of nitric oxide production in leishmania major infected macrophage cells.the present study was conducted to investigate the optimized timing for macrophages induction and nitric oxide (no) production against invading leishmania parasite.201728127337
leishmania major: genetic profiles of the parasites isolated from chabahar, southeastern iran by ppip-pcr.leishmaniasis is important vector-borne parasitic disease worldwide, caused by the genus leishmania. the objective of the current study was to identify genetic polymorphism in l. major, one of the species causing cutaneous leishmaniasis (cl), isolated from southeastern iran, using permissively primed intergenic polymorphic-polymerase chain reaction (ppip-pcr) method.201728127333
expression analysis of multiple genes may involve in antimony resistance among leishmania major clinical isolates from fars province, central iran.treatment of cutaneous leishmaniasis (cl) is being faced with serious difficulties in fars province, due to emerging of resistance against meglumine antimonite (glucantime®). in this context, determining some biomarkers for drug sensitivity monitoring seems to be highly essential. different studies have been carried out to decipher the genes might be involved in antimony resistant phenotype in leishmania spp. here, we selected three genes: aqp (as drug transporter), tdr-1-1(as drug activator), a ...201728096850
continual renewal and replication of persistent leishmania major parasites in concomitantly immune hosts.in most natural infections or after recovery, small numbers of leishmania parasites remain indefinitely in the host. persistent parasites play a vital role in protective immunity against disease pathology upon reinfection through the process of concomitant immunity, as well as in transmission and reactivation, yet are poorly understood. a key question is whether persistent parasites undergo replication, and we devised several approaches to probe the small numbers in persistent infections. we fin ...201728096392
molecular characterization of leishmania parasites in giemsa-stained slides from cases of human cutaneous and visceral leishmaniasis, eastern algeria.in algeria, visceral leishmaniasis (vl) is due to leishmania (l.) infantum, while three cutaneous forms (cl) are caused by leishmania major, leishmania tropica and leishmania infantum. in this study, the use of giemsa-stained slides was evaluated with two pcr techniques, in eastern algeria.201728301305
chroman-4-one derivatives targeting pteridine reductase 1 and showing anti-parasitic activity.flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (ptr1) inhibitors. herein, we focus our attention on the chroman-4-one scaffold. three chroman-4-one analogues (1-3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (trypanosoma brucei ptr1-tbptr1 and leishmania major-lmptr1) and parasites (trypanosoma brucei and leishmania infantum). a crystal structure of tbptr1 in complex with com ...201728282886
natural infection of nesokia indica with leishmania major and leishmania infantum parasites in damghan city, northern iran.various species of rodents are proven reservoir hosts of zoonotic cutaneous leishmaniasis in different provinces of iran and potential reservoir hosts of zoonotic visceral leishmaniasis. therefore, this study was conducted to determine the leishmanial infection of rodents in damghan city from april to september, 2015. sum of 100 rodents of three species; nesokia indica (95), mus musculus (3), and microtus socialis (2), were trapped alive and their tissue samples were examined using parasitologic ...201728267441
genomic cartography and proposal of nomenclature for the repeated, interspersed elements of the leishmania major sider2 family and identification of sider2-containing transcripts.the genomes of most eukaryotic organisms contain a large number of transposable elements that are able to move from one genomic site to another either by transferring of dna mobile elements (transposons) or transpose via reverse transcription of an rna intermediate (retroposons). an exception to this rule is found in protists of the subgenus leishmania, in which active retroposons degenerated after a flourishing era, leaving only retroposon remains; these have been classified into two families: ...201728034676
in vitro antileishmanial activity of novel azoles (3-imidazolylflavanones) against promastigote and amastigote stages of leishmania major.leishmaniasis is a protozoan infectious disease widely distributed all around the world. first line drugs including antimoniales are insufficient due to resistance in endemic areas and high toxicity. azole antifungals like ketoconazole (kcz) are also used as antileishmanial agents for several decades. in the present study, we evaluated in vitro antileishmanial effects of new azole antifungals namely 3-imidazolylflavanones (ifs) and their oximes (ifos) against leishmania major (l. major) parasite ...201728017860
a novel protein coding potential of long intergenic non-coding rnas (lincrnas) in the kinetoplastid protozoan parasite leishmania major.cutaneous leishmaniasis (cl) is caused by a kinetoplastid protozoan parasite leishmania major, as a skin ulcer at the site of the sandfly bite. cl is curable and in most cases ulcers heal spontaneously within three to six months leaving a scar and disfiguration. complete genome of l. major was reported in 2005 at the very initial phase of kinetoplastid parasite genome sequencing project. presently, l. major genome is most studied and comprehensively annotated genome and therefore, it is being us ...201727988178
parasites dampen dendritic cell activation to ensure their survival.dendritic cells (dcs) are critical for induction of protective immunity against leishmania major. however, dc activation occurs only several weeks after parasite transmission. parasites synthesize a macrophage-inducible c-type lectin (mincle) ligand. engagement of mincle by the parasite ligand dampens dc activation, thus delaying induction of interferon-γ-producing t cells responsible for parasite eradication.201727988097
molecular detection of leishmania parasites and host blood meal identification in wild sand flies from a new endemic rural region, south of iran.zoonotic cutaneous leishmaniosis (zcl) remains the most crucial vector-borne public health disease particularly in endemic rural parts of iran. the main aim of this study is to identify wild sand flies (diptera: psychodidae), determine their infection rate, and differentiate their host blood meal sources using the polymerase chain reaction-restriction fragment length polymorphism (pcr-rflp) technique. sand fly populations were caught with sticky paper traps from 10 different villages in the coun ...201727854189
comparative genomics of tunisian leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity.zoonotic cutaneous leishmaniasis caused by leishmania (l.) major parasites affects urban and suburban areas in the center and south of tunisia where the disease is endemo-epidemic. several cases were reported in human patients for which infection due to l. major induced lesions with a broad range of severity. however, very little is known about the mechanisms underlying this diversity. our hypothesis is that parasite genomic variability could, in addition to the host immunological background, co ...201727818279
amiodarone triggers induction of apoptosis in cutaneous leishmaniasis agents.leishmaniasis is a parasitic disease that is an important problem of public health worldwide. the aim of this study was to assess the cytotoxic effects of amiodarone (amd) on leishmania tropica (mhom/af/88/kk27) and l. major (mrho/ir/75/er) promastigotes and to observe the programmed cell death features. the colorimetric mtt assay was used to find l. tropica and l. major viability and the obtained results were expressed as 50% inhibitory concentration (ic50). annexin-v fluos staining was perform ...201727553974
imported cutaneous leishmaniasis caused by leishmania major in a chinese laborer who worked in saudi arabia.we report an imported case of cutaneous leishmaniasis in a 37-year-old man from saudi arabia caused by leishmania major. he presented with non-healing nodulo-ulcerative lesions with a "volcanic crater" on the lower limbs. it was clearly cutaneous leishmaniasis - a rare disease in china - as reflected by the patient's clinical history, the lesions' morphology, histopathological examination, culture and pcr analysis of the lesions. the patient was completely cured after two cycles of sodium stibog ...201727438208
cytotoxic, anti-inflammatory, and leishmanicidal activities of diterpenes isolated from the roots of caesalpinia pulcherrima.a phytochemical investigation on the chloroform extract of caesalpinia pulcherrima roots led to the isolation of ten known furanocassane diterpenoids, vouacapen-5α-ol (1), 8,9,11,14-didehydrovouacapen-5α-ol (2), 6β-cinnamoyl-7β-hydroxyvouacapen-5α-ol (3), pulcherrin a (4), pulcherrin b (5), pulcherrin j (6), pulcherrimin a (7), pulcherrimin b (8), pulcherrimin c (9), and pulcherrimin e (10). chemical transformation of 3 and 7 gave compounds 6β-hydroxyisovouacapenol c (11), 6β-cinnamoyl-7β-acetox ...201727340793
polymerase chain reaction detection and inducible nitric-oxide synthase expression of leishmania major in mice inoculated by two different routes.leishmania major needs a sensitive and specific method for proper diagnosis. this study aims to study the course and histopathology of l. major in certain tissues of experimentally infected balb/c mice after subcutaneous (sc) and intraperitoneal (ip) inoculation.201726998433
leishmania hasp and sherp genes are required for in vivo differentiation, parasite transmission and virulence attenuation in the host.differentiation of extracellular leishmania promastigotes within their sand fly vector, termed metacyclogenesis, is considered to be essential for parasites to regain mammalian host infectivity. metacyclogenesis is accompanied by changes in the local parasite environment, including secretion of complex glycoconjugates within the promastigote secretory gel and colonization and degradation of the sand fly stomodeal valve. deletion of the stage-regulated hasp and sherp genes on chromosome 23 of lei ...201728095465
in silico prediction of leishmania major-specific cd8(+) epitopes. 201728094883
interplay between a cytosolic and a cell surface carbonic anhydrase in ph homeostasis and acid tolerance of leishmania.leishmania parasites have evolved to endure the acidic phagolysosomal environment within host macrophages. how leishmania cells maintain near-neutral intracellular ph and proliferate in such a proton-rich mileu remains poorly understood. we report here that, in order to thrive in acidic conditions, leishmania major relies on a cytosolic and a cell surface carbonic anhydrase, lmca1 and lmca2, respectively. upon exposure to acidic medium, the intracellular ph of the lmca1(+/-), lmca2(+/-) and lmca ...201728062849
utility of western blot analysis for the diagnosis of cutaneous leishmaniasis.cutaneous leishmaniasis (cl) is a parasitic disease with a relatively wide distribution in different areas of the world, including iran. the parasite is mainly diagnosed microscopically, but serological approaches might be useful for diagnosis as well. this study aimed to assess the efficacy of an immunoblotting system for serodiagnosis of cutaneous leishmaniasis in iran.201726811727
comparison of parasite burden using real-time polymerase chain reaction assay and limiting dilution assay in leishmania major infected mouse.limiting dilution assay is considered as the gold standard method for quantifying the number of parasites in the animal model of leishmania infection. nowadays, real-time pcr is being increasingly applied to quantify infectious agents. in the present study, a real-time pcr assay was developed to estimate parasite burdens in lymph nodes of leishmania major infected balb/c mice. enumeration of parasites was also performed by limiting dilution assay and compared with the results of real-time pcr ba ...201726811723
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
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
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
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
comparison of proteome profiling of two sensitive and resistant field iranian isolates of leishmania major to glucantime® by 2- dimensional electrophoresis.in this study, two-dimensional gel electrophoresis (2-de) method was applied to determine and compare the protein spots expressed in the two field isolates of leishmania major and recovered from the patients who were clinically sensitive and resistant to glucantime® treatment.201725904942
effect of amphotericin b nanodisks on leishmania major infected mice.to assess the efficacy of a novel formulation of the polyene antibiotic, amphotericin b (amb), as therapy for cutaneous leishmaniasis in different mouse strains.201725584195
antileishmanial activity of ferula assa-foetida oleo gum resin against leishmania major: an in vitro study.in ayurveda, asafetida is introduced as a valuable remedy for flatulence, hysteria, nervous disorders, whooping cough, pneumonia and bronchitis in children and also considered as an aphrodisiac agent. presently, leishmaniasis is common in most countries of the world and is a serious health problem in the world. some plant medicines and natural products have a new candidate for treatment of leishmaniasis.201725624696
evaluation of methylene blue as photosensitizer in promastigotes of leishmania major and leishmania braziliensis.the cutaneous leishmaniasis is caused by the protozoan of the genus leishmania. it is considered by who as a public health issue and a neglected disease, which affects rural workers and it is also a risk to travelers in endemic areas. the conventional treatment is toxic and leads to severe side effects. the photodynamic therapy has been studied as an alternative treatment to cutaneous leishmaniasis. this study aimed to evaluate the methylene blue internalization and the impact of the pdt in the ...201728457848
differential activation of human keratinocytes by leishmania species causing localized or disseminated disease.all leishmania species parasites are introduced into mammalian skin through a sand fly bite, but different species cause distinct clinical outcomes. mouse studies suggest that early responses are critical determinants of subsequent adaptive immunity in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant cell in the epidermis. we hypothesized that leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection. ...201728647347
vaccination with a leishmania infantum hsp70-ii null mutant confers long-term protective immunity against leishmania major infection in two mice models.the immunization with genetically attenuated leishmania cell lines has been associated to the induction of memory and effector t cell responses against leishmania able to control subsequent challenges. a leishmania infantum null mutant for the hsp70-ii genes has been described, possessing a non-virulent phenotype.201728558043
new epidemiological pattern of cutaneous leishmaniasis in two pre-saharan arid provinces, southern morocco.three leishmania species are responsible of cutaneous leishmaniasis (cl) in morocco. zoonotic cl due to leishmania major and leishmania infantum, the first is known as established in the eastern arid regions, whereas the latter evolves sporadically, especially in the north. while leishmania tropica, classically considered anthroponotic, is endemic in the semi-arid regions and is largely distributed throughout the country. the aim of this study was to identify the leishmania species causing cl in ...201728527882
modeling zoonotic cutaneous leishmaniasis incidence in central tunisia from 2009-2015: forecasting models using climate variables as predictors.transmission of zoonotic cutaneous leishmaniasis (zcl) depends on the presence, density and distribution of leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence onenvironmental and climate factors. zcl in tunisia is one of the most common forms of leishmaniasis. the aim of this paper was to build a regression model of zcl cases to identify the relationship between zcl occurrence and possible risk factors, and to develop a predicting mod ...201728841642
insights into the dynamics and dissociation mechanism of a protein redox complex using molecular dynamics.leishmania major peroxidase (lmp) is structurally and functionally similar to the well-studied yeast cytochrome c peroxidase (ccp). a recent brownian dynamics study showed that l. major cytochrome c (lmcytc) associates with lmp by forming an initial complex with the n-terminal helix a of lmp, followed by a movement toward the electron transfer (et) site observed in the lmp-lmcytc crystal structure. critical to forming the active electron transfer complex is an intermolecular arg-asp ion pair at ...201728841378
structural characterization of acidic m17 leucine aminopeptidases from the tritryps and evaluation of their role in nutrient starvation in trypanosoma brucei.leucine aminopeptidase (lap) is found in all kingdoms of life and catalyzes the metal-dependent hydrolysis of the n-terminal amino acid residue of peptide or amino acyl substrates. laps have been shown to participate in the n-terminal processing of certain proteins in mammalian cells and in homologous recombination and transcription regulation in bacteria, while in parasites, they are involved in host cell invasion and provision of essential amino acids for growth. the enzyme is essential for su ...201728815215
cutaneous leishmaniasis in saudi arabia: a comprehensive overview.despite the great efforts by health authorities in kingdom of saudi arabia (ksa), cutaneous leishmaniasis (cl) continues to be a major public health problem in the country. many risk factors make ksa prone to outbreaks and epidemics; among these, rapid urbanization and the huge population movement are the most important. the disease is endemic in many parts of ksa, with the majority of cases concentrated in six regions, including al-qaseem, riyadh, al-hassa, aseer, ha'il, and al-madinah. leishma ...201728806141
promising antileishmanial effectiveness of doxorubicin and doxil against leishmania major: an in vitro assay.to evaluate the effect of doxorubicin and its pegylated liposomal formulation (doxil, caelyx) on in vitro susceptibility of promastigote and amastigote stages of leishmania major.201728756917
arginase activity of leishmania isolated from patients with cutaneous leishmaniasis.cutaneous leishmaniasis (cl) is one of the most important vector-borne parasitic diseases, highly endemic in iran, and its prevalence is increasing all over the country. arginase (arg) activity in isolated leishmania parasites from cl patients is yet to be explored. this study aimed to compare the arg activity of isolated leishmania promastigotes from cl patients with a standard strain of leishmania major and its influences on the disease pathogenesis. we recruited 16 confirmed cl patients from ...201728731592
first report on natural infection of phlebotomus sergenti with leishmania tropica in a classical focus of leishmania major in tunisia.in tunisia, chronic cutaneous leishmaniasis due to leishmania tropica is an important health problem. its spreading has not been fully elucidated. information on sandfly vectors, as well as their associated leishmania species, is of paramount importance since vector dispersion is one of the major factors responsible for pathogen dissemination. ninety-seven unfed females belonging to the genera sergentomyia and phlebotomus were collected between june and august 2015 using sticky paper traps. poly ...201728719307
in vitro and in vivo control of secondary bacterial infection caused by leishmania major.bacterial infections of cutaneous leishmaniasis cause skin ulcers on mice, resulting in increased tissue deterioration, and these infections can be controlled with liquid allicin. to isolate and identify the incidences of real secondary bacterial infections in mice, we performed the current study by injecting mice (n = 50) with leishmania major. l. major infections were initiated by an intramuscular injection of 0.1 ml roswell park memorial institute (rpmi 1640 media/mouse (10(7) promastigote/ml ...201728703780
divergent roles for ly6c+ccr2+cx3cr1+ inflammatory monocytes during primary or secondary infection of the skin with the intra-phagosomal pathogen leishmania major.inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. to define the role of monocytes during primary or secondary infection with an intra-phagosomal pathogen we employed leishmania major-red fluorescent protein (rfp) parasites and multi-color flow cytometry to define and enumerate infected and uninfected inflammatory cells in the skin. during primary infection, infected monocytes had altered maturation and were the initial mononuclear host cell for parasi ...201728666021
gallic and ellagic acids: two natural immunomodulator compounds solve infection of macrophages by leishmania major.leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from leishmania genus. conventional treatments are high costly, and promote a sort of side effects. besides, protozoan resistance to treatments has been reported. natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control para ...201728643086
a computational methodology to overcome the challenges associated with the search for specific enzyme targets to develop drugs against leishmania major.we present an approach for detecting enzymes that are specific of leishmania major compared with homo sapiens and provide targets that may assist research in drug development. this approach is based on traditional techniques of sequence homology comparison by similarity search and markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. from 67 enzymes represented by 42 enzym ...201728638238
biodistribution and in vivo antileishmanial activity of 1,2-distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine liposome-intercalated amphotericin b.1,2-distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (dshemspc) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. our previous study revealed that liposome (lip)-intercalated amphotericin b (amb) prepared from dshemspc (dshemspc-amb-lip) possesses excellent colloidal properties and in vitro antifungal and antileishmanial activities similar to those of the liposomal amb preparation ambisom ...201728630182
a dicre recombinase-based system for inducible expression in leishmania major.here we present the establishment of an inducible system based on the dimerizable cre recombinase (dicre) for controlled gene expression in the protozoan parasite leishmania. rapamycin-induced dicre activation promoted efficient flipping and expression of gene products in a time and dose-dependent manner. the dicre flipping activity induced the expression of target genes from both integrated and episomal contexts broadening the applicability of the system. we validated the system by inducing the ...201728629935
identification of etiologic agents of cutaneous leishmaniasis in palpebral position followed by effective therapy.cutaneous leishmaniasis (cl) is a self-healing lesion but prevention of complications and involvement of vital organs such as palpebra requires proper treatment.201728616411
the antileishmanial effects of lowsonia inermis and cedrus libani on leishmania major promastigotes: an in vitro study.leishmaniasis is a parasitic disease caused by different species of protozoan parasites belonging to the genus leishmania. in this study, leishmania major (mrho/ir/75/er) promastigotes were cultured at 23-25 °c in brain heart infusion (bhi) medium supplemented with 10 % heat-inactivated fetal bovine serum (fbs) and penicillin and streptomycin. antileishmanial effects of lowsonia inermis and cedrus libani methanolic extracts (0.07, 0.15, 0.31, 0.62, 1.25, 2.5, 5, 10 mg/ml) on leishmania major pro ...201728615844
autophagy downstream of endosomal toll-like receptor signaling in macrophages is a key mechanism for resistance to leishmania major infection.leishmaniasis is caused by protozoan parasites of the genus leishmania in mammalians, these parasites survive and replicate in macrophages and parasite elimination by macrophages is critical for host resistance. endosomal toll-like receptors (tlrs) have been shown to be crucial for resistance to leishmania major in vivo for example, mice in the resistant c57bl/6 genetic background that are triple-deficient for tlr3, -7, and -9 (tlr3/7/9(-/-)) are highly susceptible to l. major infection. tlr3/7/ ...201728607148
b-1 cells modulate the murine macrophage response to leishmania major infection.to investigate the modulatory effect of b-1 cells on murine peritoneal macrophages infected with leishmania major (l. major) in vitro.201728588758
crystal structure and functional analysis of leishmania major pseudoperoxidase.leishmania major pseudoperoxidase (lmpp) is a recently discovered heme protein expressed by the human pathogen. previous in vivo and in vitro studies suggest that lmpp is a crucial element of the pathogen's defense mechanism against the reactive nitrogen species peroxynitrite produced during the host immune response. to shed light on the potential mechanism of peroxynitrite detoxification, we have determined the 1.76-å x-ray crystal structure of lmpp, revealing a striking degree of homology with ...201728584975
the midgut microbiota plays an essential role in sand fly vector competence for leishmania major.for many arthropod vectors, the diverse bacteria and fungi that inhabit the gut can negatively impact pathogen colonization. our attempts to exploit antibiotic treatment of colonized phlebotomus duboscqi sand flies in order to improve their vector competency for leishmania major resulted instead in flies that were refractory to the development of transmissible infections due to the inability of the parasite to survive and to colonize the anterior midgut with infective, metacyclic stage promastig ...201728580630
a crispr cas9 high-throughput genome editing toolkit for kinetoplastids.clustered regularly interspaced short palindromic repeats (crispr), crispr-associated gene 9 (cas9) genome editing is set to revolutionize genetic manipulation of pathogens, including kinetoplastids. crispr technology provides the opportunity to develop scalable methods for high-throughput production of mutant phenotypes. here, we report development of a crispr-cas9 toolkit that allows rapid tagging and gene knockout in diverse kinetoplastid species without requiring the user to perform any dna ...201728573017
tumor suppressor p53 induces apoptosis of host lymphocytes experimentally infected by leishmania major, by activation of bax and caspase-3: a possible survival mechanism for the parasite.apoptosis of infected host macrophages by leishmania spp. is mainly addressed as one of the survival mechanisms of the parasite. however, there is no eligible data about whether tumor suppressor p53 could induce the apoptosis of host lymphocytes-treated leishmania major via the mitochondrial intrinsic pathway. in this study, the amastigotes of l. major obtained from ten cutaneous leishmaniases (cl) patients were separately isolated and cultured in n.n.n and rpmi 1640 media. l. major was definite ...201728560572
leishmania labcg1 and labcg2 transporters are involved in virulence and oxidative stress: functional linkage with autophagy.the g subfamily of abc (atp-binding cassette) transporters of leishmania include 6 genes (abcg1-g6), some with relevant biological functions associated with drug resistance and phospholipid transport. several studies have shown that leishmania labcg2 transporter plays a role in the exposure of phosphatidylserine (ps), in virulence and in resistance to antimonials. however, the involvement of this transporter in other key biological processes has not been studied.201728558770
characterization of the protein tyrosine phosphatase lmprl-1 secreted by leishmania major via the exosome pathway.similar to other intracellular pathogens, leishmania parasites are known to evade the antimicrobial effector functions of host immune cells. to date, however, only a few virulence factors have been described for leishmania major, one of the causative agents of cutaneous leishmaniasis. here, we have characterized the expression and function of an l. major phosphatase, which we termed lmprl-1. this enzyme shows a strong structural similarity to the human phosphatases of regenerating liver (prl-1, ...201728507071
tlc-uv hyphenated with maldi-tofms for the screening of invertase substrates in plant extracts.in this study, thin-layer chromatography (tlc) hyphenated with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tofms) was developed for the screening of invertase substrates in complex matrices. bfra, a specific β-d-fructofuranosidase from leishmania major, was chosen as a model enzyme to screen biological activity in plant extracts due to its capacity to hydrolyze specific carbohydrates. tlc was considered to be a reliable technique for screening substrates ( ...201728501191
pyrrole-indolinone su11652 targets the nucleoside diphosphate kinase from leishmania parasites.nucleoside diphosphate kinases (ndks) are key enzymes in the purine-salvage pathway of trypanosomatids and have been associated with the maintenance of host-cell integrity for the benefit of the parasite, being potential targets for rational drug discovery and design. the ndk from leishmania major (lmndk) and mutants were expressed and purified to homogeneity. thermal shift assays were employed to identify potential inhibitors for lmndk. calorimetric experiments, site-directed mutagenesis and mo ...201728499874
genetic metabolic complementation establishes a requirement for gdp-fucose in leishmania.to survive in its sand fly vector, the trypanosomatid protozoan parasite leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. in leishmania major strain friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (lpg). during differentiation to infective metacyclics, d-arabinopyranose (d-arap) caps the lpg side-chain galactose residues, blocking interaction with the midgut lectin ppgalec, t ...201728465349
eyelid cutaneous leishmaniasis: a case report.cutaneous leishmaniasis (cl) is the most common parasitic disease transmitted by vectors in iran. cl is endemic in many urban and rural parts of iran and usually caused by two species of leishmania as l. major and l. tropica transmitted to humans from parasite reservoirs by the bite of female sandflies. we report a case of ocular leishmaniasis with eyelid involvement presentation. the patient was a 70-yr-old housewife woman referred to health care center in city of kashan, central iran in 2012. ...201728451564
use of two-photon microscopy to study leishmania major infection of the skin.intra-vital two-photon microscopy (2p-ivm) allows for in-situ investigation of tissue organization, cell behavior and the dynamic interactions between different cell types in their natural environment. this methodology has also expanded our understanding of the immune response against pathogens. leishmania are protozoan intracellular parasites that have adapted to successfully establish infection within the context of an inflammatory response in the skin following transmission by the bite of an ...201728434998
skin-resident cd4+ t cells protect against leishmania major by recruiting and activating inflammatory monocytes.tissue-resident memory t cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by cd4+ resident memory t cells are still being defined. in this study we addressed this issue with a population of protective skin-resident, ifnγ-producing cd4+ memory t cells generated following leishmania major infection. we previously found that resident memory t cells recruit circulating effector t cells to enhance immunity. ...201728419151
leishmania major large rab gtpase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis.we previously identified a leishmania (l.) major large rab gtpase (lmlrab), a new atypical rab gtpase protein. it is highly conserved in leishmania species while displaying low level of homology with mammalian homologues. leishmania small rab gtpases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large rab gtpases proteins has not been characterized yet. we report here the immunogenicity of both recombinant rlmlrab and rlmlrabc, in individuals wi ...201728416006
an integrated approach towards the discovery of novel non-nucleoside leishmania major pteridine reductase 1 inhibitors.despite the fact that leishmania ssp are pteridine auxotrophs, dihydrofolate reductase-thymidylate synthase (dhfr-ts) inhibitors are ineffective against leishmania major. on the other hand pteridine reductase 1 (ptr1) inhibitors proved to be lethal to the parasite. aiming at identifying hits that lie outside the chemical space of known ptr1 inhibitors, pharmacophore models that differentiate true-binders from decoys and explain the structure-activity relationships of known inhibitors were employ ...201728407565
epidemiological profile of cutaneous leishmaniasis in morocco, 2004-2013.the main objective of our study is to provide a comprehensive overview of the situation of cutaneous leishmaniasis in morocco. we therefore conducted a retrospective descriptive study covering the decade 2004-2013. data were collected from the moroccan ministry of health's annual reports about the national program against leishmaniasis. these data show a regression in the cases due to leishmania major and the persistence of l. tropica transmission. mapping cutaneous leishmaniasis cases reported ...201728406415
chemical composition of mentha pulegium and rosmarinus officinalis essential oils and their antileishmanial, antibacterial and antioxidant activities.the aim of the study was the determination of the chemical composition of mentha pulegium l. and rosmarinus officinalis l. essential oils and the evaluation of their antileishmanial, antibacterial and antioxidant activities. essential oils (eos) were isolated using steam distillation and the chemical composition was determined using gc-ms analysis. the antibacterial activity was tested against ten pathogenic strains using the diffusion method, the minimum inhibitory concentration (mic) and the m ...201728821401
protein kinase c-delta (pkcδ), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice.we previously demonstrated that protein kinase c-δ (pkcδ) is critical for immunity against listeria monocytogenes, leishmania major, and candida albicans infection in mice. however, the functional relevance of pkcδ during mycobacterium tuberculosis (mtb) infection is unknown. pkcδ was significantly upregulated in whole blood of patients with active tuberculosis (tb) disease. lung proteomics further revealed that pkcδ was highly abundant in the necrotic and cavitory regions of tb granulomas in mu ...201728832027
efficacy of paromomycin-chloroquine combination therapy in experimental cutaneous leishmaniasis.the 4-aminoquinoline chloroquine (cq) is clinically used in combination with doxycycline to cure chronic q fever, as it enhances the activity of the antibiotic against the causative bacterium coxiella burnetii residing within macrophage phagolysosomes. as there is a similar cellular host-pathogen biology for leishmania parasites, this study aimed to determine whether such an approach could also be the basis for a new, improved treatment for cutaneous leishmaniasis (cl). we have evaluated the in ...201728607026
alpha alumina nanoparticle conjugation to cysteine peptidase a and b: an efficient method for autophagy induction.autophagy as a cellular pathway facilitates several immune responses against infection. it also eliminates invading pathogens through transferring content between the cytosol and the lysosomal vesicles and contributes to the cross-presentation of exogenous antigens to t lymphocytes via mhc class i pathway. autophagy induction is one of the main targets for new drugs and future vaccine formulations. nanoparticles are one of the candidates for autophagy induction. cysteine peptidase a (cpa) and cy ...201728496946
structural influences on the activity of bismuth(iii) indole-carboxylato complexes towards helicobacter pylori and leishmania.seven new bismuth(iii) complexes derived from indole-carboxylic acids have been synthesised: five are homoleptic; [bi(iaa)3] b1, [bi(ipa)3] b2, [bi(iba)3] b3, [bi(mica)3] b4, [bi(iga)3] b6, and two are heteroleptic [biph(mica)2] b5 (where iaa-h=2-(1h-indol-3-yl)acetic acid, ipa-h=3-(1h-indol-3-yl)propanoic acid, iba-h=4-(1h-indol-3-yl)butanoic acid, iga-h=2-(1h-indol-3-yl)-2-oxoacetic acid, and mica-h=1-methyl-1h-indole-3-carboxylic acid). all complexes were fully characterised by elemental anal ...201728583712
murine cutaneous leishmaniasis investigated by maldi mass spectrometry imaging.imaging mass spectrometry (ims) is recognized as a powerful tool to investigate the spatial distribution of untargeted or targeted molecules of a wide variety of samples including tissue sections. leishmania is a protozoan parasite that causes different clinical manifestations in mammalian hosts. leishmaniasis is a major public health risk in different continents and represents one of the most important neglected diseases. cutaneous lesions from mice experimentally infected with leishmania spp. ...201728783195
sensitive molecular diagnostics for cutaneous leishmaniasis.rapid diagnosis of cutaneous leishmaniasis (cl) and identification of leishmania species is highly important for the disease management. in israel, cl is caused mainly by leishmania major and leishmania tropica species.201728795077
macromolecular biosynthetic parameters and metabolic profile in different life stages of leishmania braziliensis: amastigotes as a functionally less active stage.it was recently hypothesized that leishmania amastigotes could constitute a semi-quiescent stage characterized by low replication and reduced metabolic activity. this concept developed with leishmania (leishmania) mexicana and leishmania (leishmania) major models might explain numerous clinical and sub-clinical features of leishmania (viannia) braziliensis infections, like reactivation of the disease, non-response to chemotherapy or asymptomatic infections. we compared here in vitro the prolifer ...201728742826
[cutaneous leishmaniasis in israel 2016 - an update].leishmaniasis is endemic in israel and is increasing in its frequency. the pathogens that cause cutaneous leishmaniasis (cl) in israel are leishmania major (l. major) and leishmania tropica (l. tropica). in recent years, there have been significant changes in the distribution of these species. l. major is endemic mainly in the negev, arava and the beit she'an valley. l. tropica is endemic in tiberias, northern sea of galilee, samaria and in the vicinity of jerusalem such as at kfar adumim, ma'al ...201628530056
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