Publications

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 ...	2016	26728034
therapeutic effect of scrophularia striata ethanolic extract against localized cutaneous leishmaniasis caused by leishmania major (mrho/ir/75/er).	we evaluated the effect of the ethanolic extract of scrophularia striata on the iranian strain of leishmania major (mrho/ir/75/er) both in vitro and in vivo conditions.	2016	27957441
validation of a thin-layer chromatography/densitometry method for the characterization of invertase activity.	this paper presents a kinetic study of invertase, a specific fructofuranosidase cloned from the leishmania major genome. the kinetic parameters of the β-d-fructofuranosidase from leishmania major (bfra) were determined using thin-layer chromatography (tlc) and uv-densitometry (tlc@uv) specifically developed for the separation and detection of three carbohydrates namely sucrose, glucose and fructose. separation was performed on tlc silica gel 60 f254 plates impregnated with sodium bisulphate and ...	2016	27912968
gene-specific sex effects on eosinophil infiltration in leishmaniasis.	sex influences susceptibility to many infectious diseases, including some manifestations of leishmaniasis. the disease is caused by parasites that enter to the skin and can spread to the lymph nodes, spleen, liver, bone marrow, and sometimes lungs. parasites induce host defenses including cell infiltration, leading to protective or ineffective inflammation. these responses are often influenced by host genotype and sex. we analyzed the role of sex in the impact of specific gene loci on eosinophil ...	2016	27895891
in vitro anti-leishmanial activity of satureja hortensis and artemisia dracunculus extracts on leishmania major promastigotes.	cutaneous leishmaniasis is one of the important skin diseases with diverse clinical manifestations. with an incidence of 0.7-1.3 million cases annually, this disease is often reported from six countries, including iran. accordingly, the purpose of this study was to evaluate the anti-leishmanial effect of the three plant hydroalcoholic extracts including fleawort (plantago psyllium l.), savory (satureja hortensis l.) and tarragon (artemisia dracunculus l.) on leishmania major promastigotes. the h ...	2016	27876985
evaluation of the alum-naloxone adjuvant activity against experimental murine leishmaniasis due to l. major.	leishmaniasis is caused by intracellular parasites of leishmania species, which are transmitted by the bite of the sandfly. recovery and protection against the infection depends on the induction of a strong th1 type of immune response. vaccination of mice with the opioid antagonist naloxone can promote the activation of the th1 responses. we studied the efficacy of the mixture of naloxone and alum, as an adjuvant, to enhance immune responses and induce protection against leishmania major infecti ...	2016	27876902
codelivery of dna vaccination encoding leif gene and il-12 increases protection against leishmania major infection in balb/c mice.	previous studies have shown that leishmania elongation initiation factor (leif) antigen causes a partial immunity against leishmaniasis. the antigen develops type i immunity by overexpression of inflammatory cytokines such as interleukin-12 (il-12), ifn-γ and tnf-α. therefore, we evaluated immune responses induced by the leif gene against leishmania major infection. immunization with leif gene alone or with il-12 induced th1 response and produced higher ifn-γ and lower il-4 levels by splenocytes ...	2016	26868280
cutaneous leishmaniasis: an overlooked etiology of midfacial destructive lesions.	midline destructive lesions of the face (mdl) have a wide range of etiologies. cutaneous leishmaniasis (cl) is rarely reported as a possible cause.	2016	26862748
resequencing and assembly of seven complex loci to improve the leishmania major (friedlin strain) reference genome.	leishmania parasites cause severe human diseases known as leishmaniasis. these eukaryotic microorganisms possess an atypical chromosomal architecture and the regulation of gene expression occurs almost exclusively at post-transcriptional levels. accordingly, sequencing of the genome of leishmania major, and subsequently the genome of other related species, was paramount for highlighting these peculiar molecular aspects. recently, we carried out an analysis of gene expression by massive sequencin ...	2016	26857920
molecular prevalence and estimated risk of cutaneous leishmaniasis in libya.	cutanoeus leishmaniasis (cl) is an endemic disease in the mediterranean area including libya. the aim of the present study is to detect the prevalent leishmania species obtained from smeared cutaneous lesions in addition to studying the diverse sociodemographic risk factors of the reported cases from different provinces of libya.	2016	26850321
[epidemiological and clinical features of cutaneous leishmaniasis in kairouan-tunisia and characteristics in children].	cutaneous leishmaniasis (cl) remains highly endemic in tunisia. the governorate of kairouan (center) is one of the most affected particularly by zoonotic form due to leishmania major. the purpose of this study was to describe the epidemiological, clinical and therapeutic features of the disease in this governorate and to identify any particularities in children. three hundred and ninety cases were registered over 2 years (2012 and 2013). the average age was 29 years one month [± 22.7] (34.6% of ...	2016	26850105
in vitro and in vivo antileishmanial activities of pistacia vera essential oil.	this study aims to evaluate the in vitro and in vivo antileishmanial activities of pistacia vera essential oil and compare their efficacy with a reference drug, meglumine antimoniate (glucantime®). this essential oil (0-100 µg/ml) was evaluated in vitro against the intracellular amastigote forms of leishmania tropica (mhom/ir/2002/mash2) and then tested on cutaneous leishmaniasis of male balb/c mice by leishmania major (mrho/ir/75/er). in the in vitro assay, it could be observed that p. vera ess ...	2016	26829519
targeting leishmania major parasite with peptides derived from a combinatorial phage display library.	cutaneous leishmaniasis (cl) is a global problem caused by intracellular protozoan pathogens of the genus leishmania for which there are no suitable vaccine or chemotherapy options. thus, de novo identification of small molecules binding to the leishmania parasites by direct screening is a promising and appropriate alternative strategy for the development of new drugs. in this study, we used a random linear hexapeptide library fused to the gene iii protein of m13 filamentous bacteriophage to sel ...	2016	26995695
trypanosoma cruzi polyamine transporter: its role on parasite growth and survival under stress conditions.	trypanosoma cruzi is the etiological agent of chagas disease, a major health problem in latin america. polyamines are polycationic compounds that play a critical role as regulators of cell growth and differentiation. in contrast with other protozoa, t. cruzi is auxotrophic for polyamines because of its inability to synthesize putrescine due to the lack of both, arginine and ornithine decarboxylase; therefore, the intracellular availability of polyamines depends exclusively on transport processes ...	2016	26983938
lmsmdb: an integrated database for metabolic and gene regulatory network in leishmania major and schistosoma mansoni.	a database that integrates all the information required for biological processing is essential to be stored in one platform. we have attempted to create one such integrated database that can be a one stop shop for the essential features required to fetch valuable result. lmsmdb (l. major and s. mansoni database) is an integrated database that accounts for the biological networks and regulatory pathways computationally determined by integrating the knowledge of the genome sequences of the mention ...	2016	26981382
ribosomal rna genes in the protozoan parasite leishmania major possess a nucleosomal structure.	little is known about nucleosome structure and epigenetic regulation of transcription of rrna genes in early-branched eukaryotes. here we analyze the chromatin architecture and distribution of some histone modifications in the rrna genes in the parasitic protozoon leishmania major. southern blots of mnase-partially-digested chromatin with dna probes spanning the whole rrna gene repeat showed that the intergenic spacer presents a tight nucleosomal structure, whereas the promoter region is practic ...	2016	26963795
leishmania-encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence.	leishmania major encodes 2 orthologs of the cytokine macrophage migration inhibitory factor (mif), whose functions in parasite growth or in the host-parasite interaction are unknown. to determine the importance of leishmania-encoded mif, both lmmif genes were removed to produce an mif(-/-) strain of l. major this mutant strain replicated normally in vitro but had a 2-fold increased susceptibility to clearance by macrophages. mice infected with mif(-/-) l. major, when compared to the wild-type st ...	2016	26956417
tamoxifen induces apoptosis of leishmania major promastigotes in vitro.	tamoxifen is an antagonist of the estrogen receptor and currently used for the treatment of breast cancer. the current treatment of cutaneous leishmaniasis with pentavalent antimony compounds is not satisfactory. therefore, in this study, due to its antileishmanial activity, effects of tamoxifen on the growth of promastigotes and amastigotes of leishmania major iranian strain were evaluated in vitro. promastigotes and amastigotes were treated with different concentrations (1, 5, 10, 20, and 50 μ ...	2016	26951973
zinc(ii)-dipicolylamine coordination complexes as targeting and chemotherapeutic agents for leishmania major.	cutaneous leishmaniasis is a neglected tropical disease that causes painful lesions and severe disfigurement. modern treatment relies on a few chemotherapeutics with serious limitations, and there is a need for more effective alternatives. this study describes the selective targeting of zinc(ii)-dipicolylamine (zndpa) coordination complexes toward leishmania major, one of the species responsible for cutaneous leishmaniasis. fluorescence microscopy of l. major promastigotes treated with a fluores ...	2016	26926632
atenolol reduces leishmania major-induced hyperalgesia and tnf-α without affecting il-1β or keratinocyte derived chemokines (kc).	infection with a high dose of the intracellular parasitic protozoan leishmania major induces a sustained hyperalgesia in susceptible balb/c mice accompanied by up-regulation of the pro-inflammatory cytokines il-1β and il-6. interleukin-13 (il-13) has been shown to reduce this hyperalgesia (despite increased levels of il-6) and the levels of il-1β during and after the treatment period. these findings favor the cytokine cascade leading to the production of sympathetic amines (involving tnf-α and k ...	2016	26913003
the glycerol-3-phosphate acyltransferase tbgat is dispensable for viability and the synthesis of glycerolipids in trypanosoma brucei.	glycerolipids are the main constituents of biological membranes in trypanosoma brucei, which causes sleeping sickness in humans. importantly, they occur as a structural component of the glycosylphosphatidylinositol lipid anchor of the abundant cell surface glycoproteins procyclin in procyclic forms and variant surface glycoprotein in bloodstream form, that play crucial roles for the development of the parasite in the insect vector and the mammalian host, respectively. the present work reports th ...	2016	26909872
evaluation of the in vivo leishmanicidal activity of amphotericin b emulgel: an alternative for the treatment of skin leishmaniasis.	the american cutaneous leishmaniasis (acl) is an infectious disease that can be fatal. the first line of treatment is pentavalent antimonies. however, due to its potential to develop resistance, amphotericin b (amb) started to be used as an alternative medicine. current treatments are limited, a fact that has led to a growing interesting in developing new therapies. this study aims to evaluate the therapeutic potential in vivo of an amphotericin b + oleic acid (oa) emulgel in the treatment of cu ...	2016	26902606
computing molecular devices in l.major through transcriptome analysis: structured simulation approach.	in the modern era of post genomics and transcriptomics, non-coding rnas and non-coding regions of many rnas are a big puzzle when we try deciphering their role in specific gene function. gene function assessment is a main task wherein high throughput technologies provide an impressive body of data that enables the design of hypotheses linking genes to phenotypes. gene knockdown technologies and rna-dependent gene silencing are the most frequent approaches to assess the role of key effectors in a ...	2016	26901858
oral treatment with zinc sulfate increases the expression of th1 cytokines mrna in balb/c mice infected with leishmania major.	leishmaniases consist of a group of diseases caused by protozoan parasites of leishmania genus. the outcome of the disease depends on the immune responses of the host as well as the pathogenicity of the strain of the parasite. in murine models, the inoculation of leishmania major into resistant mice results in th1 responses and recovery from the infection. however in the susceptible mice, the same inoculation leads to a profile of th2 responses. zinc (zn) is an essential trace element which is r ...	2016	26896749
the wnt antagonist dickkopf-1 promotes pathological type 2 cell-mediated inflammation.	exposure to a plethora of environmental challenges commonly triggers pathological type 2 cell-mediated inflammation. here we report the pathological role of the wnt antagonist dickkopf-1 (dkk-1) upon allergen challenge or non-healing parasitic infection. the increased circulating amounts of dkk-1 polarized t cells to t helper 2 (th2) cells, stimulating a marked simultaneous induction of the transcription factors c-maf and gata-3, mediated by the kinases p38 mapk and sgk-1, resulting in th2 cell ...	2016	26872695
lipid droplet formation, their localization and dynamics during leishmania major macrophage infection.	leishmania, the causative agent of vector-borne diseases, known as leishmaniases, is an obligate intracellular parasite within mammalian hosts. the outcome of infection depends largely on the activation status of macrophages, the first line of mammalian defense and the major target cells for parasite replication. understanding the strategies developed by the parasite to circumvent macrophage defense mechanisms and to survive within those cells help defining novel therapeutic approaches for leish ...	2016	26871576
cutaneous leishmaniasis of the eyelids: a case series with molecular identification and literature review.	cutaneous leishmaniasis (cl) is a protozoan disease which is endemic in iran. it is transmitted by the phlebotomus sand fly. the eyelid is rarely involved possibly because the movement of the lids impedes the sand fly from biting the skin in this region. here, we report 6 rare cases of eyelid cl. the patients were diagnosed by skin scraping, culture, and pcr from the lesions. skin scraping examination showed leishmania spp. amastigotes in the cytoplasm of macrophages. culture examination was pos ...	2016	28095664
determination the role of rhipicephalus sanguineus for transmission of leishmania major to reservoir animals.	this study aimed to explore the role of rhipicephalus sanguineus in the transmission of leishmania major, the etiological agent of zoonotic cutaneous leishmaniasis.	2016	28091384
aquaglyceroporin1 gene expression in antimony resistance and susceptible leishmania major isolates.	the mechanism of antimony resistance in leishmania has been studied extensively, in connection with decreased influx and/or increased eflux of the drug. aquaporin 1 (aqp1) protein has been shown to mediate the uptake of trivalent antimony. this study was aimed to find the expression level of aqp1 gene in resistant versus non-resistant clinical isolates of leishmania major in iranian patients.	2016	28035115
an in vitro study of antileishmanial effect of portulaca oleracea extract.	leishmaniasis is caused by protozoa of leishmania genus and is considered as a zoonotic disease. it is a major public health problem worldwide, with high endemicity in developing countries like iran. various chemical drugs are used for leishmaniasis treatment, but their side-effects and the emergence of drug resistance have led to look for new effective compounds. the aim of this study was to introduce purslane (portulaca oleracea) as a traditional and medicinal herb which might act as a valuabl ...	2016	28035114
myeloid cell-derived hif-1α promotes control of leishmania major.	hypoxia-inducible factor-1α (hif-1α), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. however, whether and to what extent hif-1α expressed by myeloid cells contributes to the innate immune response against leishmania major parasites is unknown. we observed that leishmania-infected humans and l. major-infected c57bl/6 mice exhibited substantial amounts of hif-1α in acute cutaneous lesions. in vitro, hif-1α was required for leishman ...	2016	27798163
epidemiology of the outbreak, vectors and reservoirs of cutaneous leishmaniasis in mali: a systematic review and meta-analysis.	to compile available data and to estimate the burden, characteristics and risks factors of cutaneous leishmaniasis (cl) in mali.	2016	27794393
ruthenium-clotrimazole complex has significant efficacy in the murine model of cutaneous leishmaniasis.	in previous studies we reported a novel series of organometallic compounds, ru(ii) complexed with clotrimazole, displaying potent trypanosomatid activity with unnoticeable toxicity toward normal mammalian cells. in view of the promising activity of ru-clotrimazole complexes against leishmania major (l. major), the present work sought to investigate the anti-leishmanial activity of the am162 complex in the murine model of cutaneous leishmaniasis. in addition, to facilitate the design of new thera ...	2016	27693373
topical treatment with a two-component gel releasing nitric oxide cures c57bl/6 mice from cutaneous leishmaniasis caused by leishmania major.		2016	27249422
anti leishmania activity of lucilia sericata and calliphora vicina maggots in laboratory models.	use of sterile fly larvae (maggots) of blow flies for the treatment of many different types of skin and soft tissue wounds is called maggot debridement therapy (mdt). the larvae of blow flies secrete a broad spectrum of compounds with diverse mechanisms of action in the gut and salivary glands called excretion/secretion (es) products which showed to have antimicrobial activities against gram negative and positive bacteria. cutaneous leishmaniasis (cl) which is the common form of leishmaniasis is ...	2016	27567983
a label-free, pcr-free and signal-on electrochemical dna biosensor for leishmania major based on gold nanoleaves.	detection of leishmaniasis is important in clinical diagnoses. in the present study, identification of leishmania parasites was performed by a label-free, pcr-free and signal-on ultrasensitive electrochemical dna biosensor. gold nanoleaves were firstly electrodeposited by an electrodeposition method using spermidine as a shape directing agent. the biosensor was fabricated by immobilization of a leishmania major specific dna probe onto gold nanoleaves, and methylene blue was employed as a marker. ...	2016	27769435
leishmania major cutaneous leishmaniasis in 3 travelers returning from israel to the netherlands.		2016	27767930
leishmania uses mincle to target an inhibitory itam signaling pathway in dendritic cells that dampens adaptive immunity to infection.	c-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. here, we have found that human and mouse mincle bind to a ligand released by leishmania, a eukaryote parasite that evades an effective immune response. mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after leishmania major intradermal ear infection. mincle deficiency enhanced adaptive immunity against the parasite, ...	2016	27742545
toll-like receptor 2 (tlr2) plays a role in controlling cutaneous leishmaniasis in vivo, but does not require activation by parasite lipophosphoglycan.	leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide. despite several studies reporting involvement of the innate immune receptor toll-like receptor 2 (tlr2) in the recognition of surface glycolipids from leishmania parasites in vitro, the role of tlr2 and its co-receptors during cutaneous leishmaniasis infection in vivo is unknown.	2016	27716391
molecular characterization of 5s ribosomal rna genes and transcripts in the protozoan parasite leishmania major.	eukaryotic 5s rrna, synthesized by rna polymerase iii (pol iii), is an essential component of the large ribosomal subunit. most organisms contain hundreds of 5s rrna genes organized into tandem arrays. however, the genome of the protozoan parasite leishmania major contains only 11 copies of the 5s rrna gene, which are interspersed and associated with other pol iii-transcribed genes. here we report that, in general, the number and order of the 5s rrna genes is conserved between different species ...	2016	27707420
exploring the leishmania hydrophilic acylated surface protein b (haspb) export pathway by live cell imaging methods.	leishmania major is a human-infective protozoan parasite transmitted by the bite of the female phlebotomine sand fly. the l. major hydrophilic acylated surface protein b (haspb) is only expressed in infective parasite stages suggesting a role in parasite virulence. haspb is a "nonclassically" secreted protein that lacks a conventional signal peptide, reaching the cell surface by an alternative route to the classical er-golgi pathway. instead haspb trafficking to and exposure on the parasite plas ...	2016	27665560
an epidemic outbreak of cutaneous leishmaniasis presenting as suppurative folliculitis: a study of 6 cases.	folliculitis is defined as the inflammation of the follicles. the most common cause of folliculitis is infection. here, we report an unusual cause of suppurative infundibulitis-which had not yet been described in the literature-due to leishmania infection, and exemplified by 6 cases that occurred in the setting of an epidemic outbreak. the 6 individuals were immigrants from morocco. most of them were men (4 men and 2 women), and most of them were less than 30 years old (apart from one 40-year-ol ...	2016	27655127
immunization against cutaneous leishmaniasis by alginate microspheres loaded with autoclaved leishmania major (alm) and quillaja saponins.	leishmania antigens are weak immunogens and need to be potentiated by various adjuvants and delivery systems. alginate microspheres as antigen delivery system and quillaja saponins (qs) as immunoadjuvant have been used to enhance the immune response against autoclaved leishmania major (alm). microspheres were prepared by an emulsification technique and characterized for size, encapsulation efficiency and release profile of encapsulates. balb/c mice were immunized three times in 3-weeks intervals ...	2016	27642328
study of genetic variation of leishmania major based on internal transcribed spacer 1 (its1) in chabahar, iran.	zoonotic cutaneous leishmaniasis (zcl) is polymorphic disease that may show various clinical manifestations.	2016	27635211
topical simvastatin as host-directed therapy against severity of cutaneous leishmaniasis in mice.	we recently demonstrated that statins mediate protection against intracellular pathogens, mycobacterium tuberculosis and listeria monocytogenes in mice. here, we investigated the immunomodulatory potential of simvastatin as a topical or systemic host-directed drug therapy in controlling inflammatory responses in an experimental mouse model of cutaneous leishmaniasis caused by leishmania major (lv39). in an ear infection model, topical application of simvastatin directly on established lesions si ...	2016	27632901
t helper 1 (th1), th2, and th17 responses to leishmania major lipophosphoglycan 3.	leishmania major is the main causal agent of cutaneous leishmaniasis (cl) that remains a serious public health concern in many tropical and subtropical countries. a long-lasting protective vaccine against leishmaniasis remains as a medical unmet need. lipophosphoglycan 3 (lpg3) is one of the class ii lpg genes from hsp90 family involved in the host immune responses. the aim of the present study is to investigate the capability of recombinant lpg3 (rlpg3) to induce th1, th2, th17 responses. the r ...	2016	27611455
characterization of a novel endoplasmic reticulum protein involved in tubercidin resistance in leishmania major.	tubercidin (tub) is a toxic adenosine analog with potential antiparasitic activity against leishmania, with mechanism of action and resistance that are not completely understood. for understanding the mechanisms of action and identifying the potential metabolic pathways affected by this drug, we employed in this study an overexpression/selection approach using tub for the identification of potential targets, as well as, drug resistance genes in l. major. although, tub is toxic to the mammalian h ...	2016	27606425
the role of montanide isa 70 as an adjuvant in immune responses against leishmania major induced by thiol-specific antioxidant-based protein vaccine.	leishmaniasis is a parasitic disease caused by several species of the genus leishmania. montanide isa 70 is an adjuvant composed of a natural metabolizable oil and a very refined emulsifier from the manide monooleate family. the tsa (thiol-specific antioxidant) is a important antigen of leishmania major. the purpose of this work was protein-vaccine efficacy as an protection and excellent candidate in the presence montanide. the expression of recombinant protein was confirmed with sds (sodium dod ...	2016	27605780
in vitro efficacy of ethanolic extract of artemisia absinthium (asteraceae) against leishmania major l. using cell sensitivity and flow cytometry assays.	leishmaniasis is one of the most neglected human diseases with an estimated global burden ranking second in mortality and fourth in morbidity among the tropical infections. chemotherapy involving the use of drugs like glucantime is the mainstay treatment in endemic areas of iran. drug resistance is increasingly prevalent, so search for alternative therapy is gathering pace. medicinal herbs, like wormwood artemisia, have chemical compounds effective against a number of pathogens. in this study, t ...	2016	27605775
in vivo/in vitro immune responses to l. major isolates from patients with no clinical response to glucantime.	leishmaniasis is a major health problem in some endemic areas of tropical and subtropical areas of the world. interleukin-12 (il-12) and interferon gamma (ifn-γ) are essential cytokines associated with initiation of th1 response. the main objective of this study was to evaluate of the type of immune response to l. major isolates from patients with no clinical response to antimonite (glucantime).	2016	27563636
anti-leishmanial activity (in vitro and in vivo) of allicin and allicin cream using leishmania major (sub-strain zymowme lon4) and balb/c mice.	leishmania is a unicellular protozoan parasite that produces several human diseases, ranging from localized self-healing cutaneous lesions to deadly visceral infections.	2016	27537199
crystal structure of an fe-s cluster-containing fumarate hydratase enzyme from leishmania major reveals a unique protein fold.	fumarate hydratases (fhs) are essential metabolic enzymes grouped into two classes. here, we present the crystal structure of a class i fh, the cytosolic fh from leishmania major, which reveals a previously undiscovered protein fold that coordinates a catalytically essential [4fe-4s] cluster. our 2.05 å resolution data further reveal a dimeric architecture for this fh that resembles a heart, with each lobe comprised of two domains that are arranged around the active site. besides the active site ...	2016	27528683
structure-guided discovery of thiazolidine-2,4-dione derivatives as a novel class of leishmania major pteridine reductase 1 inhibitors.	leishmania major, as other protozoan parasites, plague human kind since pre-historic times but it remains a worldwide ailment for which the therapeutic arsenal remains scarce. although l. major is pteridine- and purine-auxotroph, well-established folate biosynthesis inhibitors, such as methotrexate, have poor effect over the parasite survival. the lack of efficiency is related to an alternative biochemical pathway in which pteridine reductase 1 (ptr1) plays a major role. for this reason, this en ...	2016	27517809
transcriptionally driven dna replication program of the human parasite leishmania major.	faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple dna replication origins (oris). although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite leishmania major, building on a better evolutionary understanding of replication organization in eukarya. we found tha ...	2016	27477279
leishmania major infection-induced vegf-a/vegfr-2 signaling promotes lymphangiogenesis that controls disease.	cutaneous leishmaniasis causes a spectrum of diseases from self-healing to severe nonhealing lesions. defining the factors contributing to lesion resolution may help in developing new therapies for those patients with chronic disease. we found that infection with leishmania major increases the expression of vascular endothelial growth factor-a and vascular endothelial growth factor receptor (vegfr)-2 and is associated with significant changes in the blood and lymphatic vasculature at the site of ...	2016	27474074
antileishmanial, antioxidant, and cytotoxic activities of quercus infectoria olivier extract.	currently, there is no effective vaccine available, and chemotherapy is the main approach for treatment of cutaneous leishmaniasis (cl). during recent decades, studies have demonstrated that a number of plant-derived compounds may act as new therapeutic tools against leishmaniasis. this study was evaluated the antileishmanial, antioxidant, and cytotoxic activities of quercus infectoria olivier (oak) extract. the total amount of phenolic and flavonoid compounds was measured in oak extract. high p ...	2016	27470357
comparing acute and chronic human cutaneous leishmaniasis caused by leishmania major and leishmania tropica focusing on arginase activity.	cutaneous leishmaniasis (cl) in iran is mainly caused by leishmania major (l. major) and l. tropica. arginase mediated l-arginine metabolism is an important issue in leishmania parasite propagation. arginase activity in human cl due to l. major and l. tropica have not been studied up to now.	2016	27439742
effect of topical morphine on cutaneous leishmaniasis in an animal model: a preliminary report.	pentavalent antimonials remain the choice of treatment for leishmaniasis, despite their toxicity, high cost, and difficult administration. as an alternative, morphine may induce the healing process of cutaneous leishmaniasis by its immunoregulatory characteristics.	2016	27437123
transcription of leishmania major u2 small nuclear rna gene is directed by extragenic sequences located within a trna-like and a trna-ala gene.	leishmania and other trypanosomatid parasites possess atypical mechanisms of gene expression, including the maturation of mrnas by trans-splicing and the involvement of rna polymerase iii in transcription of all snrna molecules. since snrnas are essential for trans-splicing, we are interested in the study of the sequences that direct their expression. here we report the characterization of l. major u2 snrna promoter region.	2016	27430335
oral azithromycin versus its combination with miltefosine for the treatment of experimental old world cutaneous leishmaniasis.	leishmaniasis is one of the neglected infectious diseases included in the world health organization's list of the top guns of antimicrobial resistance. miltefosine is the first and the only available oral effective therapy for leishmaniasis. for fear of its potential resistance, identification of alternative, effective and safe drugs is urgently needed. therefore, in view of azithromycin promising activity against a number of leishmania species, this work was carried out to evaluate the efficacy ...	2016	27413324
immune responses in dna vaccine formulated with pmma following immunization and after challenge with leishmania major.	leishmaniasis is a major infectious disease caused by protozoan parasites of the genus leishmania. despite of many efforts toward vaccine against leishmania no effective vaccine has been approved yet. dna vaccines can generate more powerful and broad immune responses than conventional vaccines. in order to increase immunity, the dna vaccine has been supplemented with adjuvant. in this study a new nano-vaccine containing tsa recombinant plasmid and poly(methylmethacrylate) nanoparticles (act as a ...	2016	27413316
pathways leading to interleukin-12 production and protective immunity in cutaneous leishmaniasis.	leishmaniasis affects millions of people worldwide and continues to pose public health problem. there is extensive evidence supporting the critical role for il-12 in initiating and maintaining protective immune response to leishmania infection. although gene deletion studies show that cd40-cd40l interaction is an important pathway for il-12 production by antigen-presenting cells and subsequent development of protective immunity in cutaneous leishmaniasis, several studies have uncovered other pat ...	2016	27394077
insights into the structural patterns of the antileishmanial activity of bi- and tricyclic n-heterocycles.	the influence of various structural patterns in a series of novel bi- and tricyclic n-heterocycles on the activity against leishmania major and leishmania panamensis has been studied and compounds that are active in the low micromolar region have been identified. both quinolines and tetrahydrooxazinoindoles (toi) proved to have significant antileishmanial activities, while substituted indoles were inactive. we have also showed that a chloroquine analogue induces leishmania killing by modulating ...	2016	27376396
concomitant immunity induced by persistent leishmania major does not preclude secondary re-infection: implications for genetic exchange, diversity and vaccination.	many microbes have evolved the ability to co-exist for long periods of time within other species in the absence of overt pathology. evolutionary biologists have proposed benefits to the microbe from 'asymptomatic persistent infections', most commonly invoking increased likelihood of transmission by longer-lived hosts. typically asymptomatic persistent infections arise from strong containment by the immune system, accompanied by protective immunity; such 'vaccination' from overt disease in the pr ...	2016	27352043
lack of galectin-3 increases jagged1/notch activation in bone marrow-derived dendritic cells and promotes dysregulation of t helper cell polarization.	galectin-3, an endogenous glycan-binding protein, is abundantly expressed at sites of inflammation and immune cell activation. although this lectin has been implicated in the control of t helper (th) polarization, the mechanisms underlying this effect are not well understood. here, we investigated the role of endogenous galectin-3 during the course of experimental leishmania major infection using galectin-3-deficient (lgals3(-/-)) mice in a balb/c background and the involvement of notch signalin ...	2016	27344022
leishmania major promastigotes evade lc3-associated phagocytosis through the action of gp63.	the protozoan leishmania parasitizes macrophages and evades the microbicidal consequences of phagocytosis through the inhibition of phagolysosome biogenesis. in this study, we investigated the impact of this parasite on lc3-associated phagocytosis, a non-canonical autophagic process that enhances phagosome maturation and functions. we show that whereas internalization of l. major promastigotes by macrophages promoted lc3 lipidation, recruitment of lc3 to phagosomes was inhibited through the acti ...	2016	27280768
an electrochemical genosensor for leishmania major detection based on dual effect of immobilization and electrocatalysis of cobalt-zinc ferrite quantum dots.	identification of leishmania parasites is important in diagnosis and clinical studies of leishmaniasis. although epidemiological and clinical methods are available, they are not sufficient for identification of causative agents of leishmaniasis. in the present study, quantum dots of magnetic cobalt-zinc ferrite (co0.5zn0.5fe2o4) were synthesized and characterized by physicochemical methods. the quantum dots were then employed as an electrode modifier to immobilize a 24-mer specific single strand ...	2016	27260450
antileishmanial activity of date (phoenix dactylifera l) fruit and pit extracts in vitro.	leishmaniasis is considered as a major public health problem worldwide. current drugs in treatment of leishmaniasis have some limitations; thus, the current study was aimed to assess the methanolic extracts of pit and fruit of phoenix dactylifera against leishmania major promastigotes. l major promastigotes were cultured in rpmi 1640 and incubated at 25°c ± 1°c for 24, 48, and 72 hours. for obtaining the ic50 (half maximal inhibitory concentration) value, mtt assay was employed. furthermore, pro ...	2016	27242378
leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages.	phosphatase activity of leishmania spp. has been shown to deregulate the signalling pathways of the host cell. we here show that leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the promastigote secretion medium (psm) as compared with the amastigote secretion medium (asm) and was not due to cell lysis, since parasite viability was not affected by the secretion process. the biochemical characterization showed t ...	2016	27220404
correlation of genetic heterogeneity with cytopathological and epidemiological findings of leishmania major isolated from cutaneous leishmaniasis in southern iran.	cutaneous leishmaniasis (cl) has recently grown into a major public health problem in 88 countries of the world, including iran. it is a polymorphic disease which may show various clinicopathological features. although the effect of the genetic diversity of the parasite has been demonstrated as one of the factors influencing clinical manifestations in cl, no data exist regarding the genetic variation of leishmania major and its microscopical features.	2016	27215312
unraveling the alkaline phosphatase inhibition, anticancer, and antileishmanial potential of coumarin-triazolothiadiazine hybrids: design, synthesis, and molecular docking analysis.	a series of new coumarin-triazolothiadiazine hybrid compounds (5a-j) was designed and synthesized by using the molecular hybridization concept. the cyclocondensation reaction involves the coumarinyl 4-amino-1,2,4-triazole and a range of bromo-acetophenones, delivering the desired products in good yields. the structures of the synthesized compounds were established on the basis of spectro-analytical data. the prepared compounds were evaluated against alkaline phosphatase (alp) where compound 5j i ...	2016	27214743
leishmania major and trypanosoma cruzi present distinct dna damage responses.	leishmania major and trypanosoma cruzi are medically relevant parasites and interesting model organisms, as they present unique biological processes. despite increasing data regarding the mechanisms of gene expression regulation, there is little information on how the dna damage response (ddr) occurs in trypanosomatids. we found that l. major presented a higher radiosensitivity than t. cruzi. l. major showed g1 arrest and displayed high mortality in response to ionizing radiation as a result of ...	2016	27188657
cathepsin b-deficient mice resolve leishmania major inflammation faster in a t cell-dependent manner.	a critical role for intracellular tlr9 has been described in recognition and host resistance to leishmania parasites. as tlr9 requires endolysosomal proteolytic cleavage to achieve signaling functionality, we investigated the contribution of different proteases like asparagine endopeptidase (aep) or cysteine protease cathepsins b (catb), l (catl) and s (cats) to host resistance during leishmania major (l. major) infection in c57bl/6 (wt) mice and whether they would impact on tlr9 signaling. unli ...	2016	27182703
human immune response to salivary proteins of wild-caught phlebotomus papatasi.	phlebotomine sand flies are the known vectors of leishmania parasites. new approaches in vaccination against leishmania have investigated the possibility of integrating phlebotomus papatasi salivary proteins to enhance the immune response and protect against the transmission of the infection. the aim of the present study was to screen human immune responses to wild sand fly saliva and evaluate immunogenic salivary proteins. blood samples were collected from donors in control and sand fly infeste ...	2016	27160331
aryl hydrocarbon receptor influences nitric oxide and arginine production and alters m1/m2 macrophage polarization.	the aryl hydrocarbon receptor (ahr) is a ligand-activated transcription factor that mediates the toxicity of environmental pollutants. it is also implicated in the regulation of the immune system. ahr-null macrophages overproduce several proinflammatory cytokines following lps-mediated stimulation, suggesting that ahr affects the balance between the inflammatory m1 and anti-inflammatory m2 phenotypes. therefore, the present study aimed to examine whether the loss of ahr modifies macrophage polar ...	2016	27153778
ecological niche modeling of main reservoir hosts of zoonotic cutaneous leishmaniasis in iran.	zoonotic cutaneous leishmaniasis (zcl), caused by leishmania major, is a common zoonotic vector-borne disease in iran. close contact with infected reservoir hosts increases the probability of transmission of leishmania parasite infections to susceptible humans. four gerbil species (rodentia: gerbillidae) serve as the main reservoir hosts for zcl in different endemic foci of iran. these species include rhombomys opimus, meriones libycus, meriones hurrianae and tatera indica; while notable infecti ...	2016	27150212
real-time pcr using fret technology for old world cutaneous leishmaniasis species differentiation.	recently, there has been a re-emergence of cutaneous leishmaniasis in endemic countries and an increase in imported cases in non-endemic countries by travelers, workers, expatriates, immigrants, and military force personnel. old world cutaneous leishmaniasis is caused primarily by leishmania major, l. tropica and l. aethiopica. despite their low sensitivity, diagnosis traditionally includes microscopic and histopathological examinations, and in vitro cultivation. several conventional pcr techniq ...	2016	27141967
genetic micro-heterogeneity of leishmania major in emerging foci of zoonotic cutaneous leishmaniasis in tunisia.	tunisia is endemic for zoonotic cutaneous leishmaniasis (zcl), a parasitic disease caused by leishmania (l.) major. zcl displays a wide clinical polymorphism, with severe forms present more frequently in emerging foci where naive populations are dominant. in this study, we applied the multi-locus microsatellite typing (mlmt) using ten highly informative and discriminative markers to investigate the genetic structure of 35 tunisian leishmania (l.) major isolates collected from patients living in ...	2016	27137082
validation of n-myristoyltransferase as potential chemotherapeutic target in mammal-dwelling stages of trypanosoma cruzi.	trypanosoma cruzi causes chagas disease, an endemic and debilitating illness in latin america. lately, owing to extensive population movements, this neglected tropical disease has become a global health concern. the two clinically available drugs for the chemotherapy of chagas disease have rather high toxicity and limited efficacy in the chronic phase of the disease, and may induce parasite resistance. the development of new anti-t. cruzi agents is therefore imperative. the enzyme n-myristoyltra ...	2016	27128971
molecular epidemiological survey of cutaneous leishmaniasis in two highly endemic metropolises of iran, application of fta cards for dna extraction from giemsa-stained slides.	pcr has been used for confirmation of leishmaniasis in epidemiological studies, but complexity of dna extraction and pcr approach has confined its routine use in developing countries.	2016	27127596
base j represses genes at the end of polycistronic gene clusters in leishmania major by promoting rnap ii termination.	the genomes of kinetoplastids are organized into polycistronic gene clusters that are flanked by the modified dna base j. previous work has established a role of base j in promoting rna polymerase ii termination in leishmania spp. where the loss of j leads to termination defects and transcription into adjacent gene clusters. it remains unclear whether these termination defects affect gene expression and whether read through transcription is detrimental to cell growth, thus explaining the essenti ...	2016	27125778
tnf-mediated restriction of arginase 1 expression in myeloid cells triggers type 2 no synthase activity at the site of infection.	neutralization or deletion of tumor necrosis factor (tnf) causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. here, we found that tnf antagonized alternative activation of macrophages and dendritic cells by il-4. tnf inhibited il-4-induced arginase 1 (arg1) expression by decreasing histone acetylation, without affecting stat6 phosphorylation and nuclear translocation. in leishmania major-infected c57bl/6 wild-type mice, ...	2016	27117406
anti-leishmania activity of osthole.	treatment of cutaneous leishmaniasis (cl) is occasionally highly resistant to pentavalent antimonials, the gold standard in pharmacotherapy of cl. since there is no effective vaccine, the discovery of natural antileishmanial products as complementary therapeutic agents could be used to improve the current regimens.	2016	27114685
the role of iscomatrix bilayer composition to induce a cell mediated immunity and protection against leishmaniasis in balb/c mice.	development of new generation of vaccines against leishmaniasis is possible because long-term protection is usually seen after recovery from cutaneous leishmaniasis. iscomatrix is particulate antigen delivery system composed of antigen, cholesterol, phospholipid and saponin. in this study, the role of iscomatrix bilayer composition made by different phase transition temperature (tc) to induce a type of immune response and protection against leishmaniasis was assessed.	2016	27081463
detection of leishmania major dna within wild caught phlebotomus papatasi and species composition of sand flies in endemic focus of cutaneous leishmaniasis, in western iran.	cutaneous leishmaniasis is one of the most important public health problem in many developing countries. the present study was conducted to determine the vector(s), the parasite and the species composition of sand flies in the dehloran county during may-november 2012. sand flies were collected by sticky traps and mounted in puri's medium for species identification. polymerase chain reaction (pcr) techniques of kdna, its1-rdna, followed by restriction fragment length polymorphism (rflp) were used ...	2016	27065601
plasmenylethanolamine synthesis in leishmania major.	ethanolamine glycerophospholipids are ubiquitous cell membrane components. trypanosomatid parasites of the genus leishmania synthesize the majority of their ethanolamine glycerophospholipids as 1-o-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine or plasmenylethanolamine (pme) through the kennedy pathway. pme is a subtype of ether phospholipids also known as ethanolamine plasmalogen whose functions are not well characterized. in this study, we investigated the role of pme synthesis in leishma ...	2016	27062077
coadminstration of l. major amastigote class i nuclease (rlmacin) with lpd nanoparticles delays the progression of skin lesion and the l. major dissemination to the spleen in balb/c mice-based experimental setting.	human cutaneous leishmaniasis is a disease caused by eukaryotic single-celled leishmania species, the developmental program of which relies upon blood-feeding adult female sand flies and their dominant mammal blood sources, namely wild rodents in area where human beings exert more or less transient activities. the recourse to model rodents - namely laboratory mice such as c57bl/6 mice - has allowed extracted the immune signatures that account for the healing of the transient cutaneous lesion tha ...	2016	27060774
leishmaniasis in turkey: first clinical isolation of leishmania major from 18 autochthonous cases of cutaneous leishmaniasis in four geographical regions.	to report isolation of leishmania major strains obtained from 18 turkish autochthonous cutaneous leishmaniasis (cl) patients infected with l. major between 2011 and 2014.	2016	27037747
the labcg2 transporter from the protozoan parasite leishmania is involved in antimony resistance.	treatment for leishmaniasis, which is caused by leishmania protozoan parasites, currently relies on a reduced arsenal of drugs. however, the significant increase in the incidence of drug therapeutic failure and the growing resistance to first-line drugs like antimonials in some areas of northern india and nepal limit the control of this parasitic disease. understanding the molecular mechanisms of resistance in leishmania is now a matter of urgency to optimize drugs used and to identify novel dru ...	2016	27021316
identification of "preferred" human kinase inhibitors for sleeping sickness lead discovery. are some kinases better than others for inhibitor repurposing?	a kinase-targeting cell-based high-throughput screen (hts) against trypanosoma brucei was recently reported, and this screening set included the published kinase inhibitor set (pkis). from the pkis was identified 53 compounds with pec50 ≥ 6. utilizing the published data available for the pkis, a statistical analysis of these active antiparasitic compounds was performed, allowing identification of a set of human kinases having inhibitors that show a high likelihood for blocking t. brucei cellular ...	2016	26998514
nyvac vector modified by c7l viral gene insertion improves t cell immune responses and effectiveness against leishmaniasis.	the nyvac poxvirus vector is used as vaccine candidate for hiv and other diseases, although there is only limited experimental information on its immunogenicity and effectiveness for use against human pathogens. here we defined the selective advantage of nyvac vectors in a mouse model by comparing the immune responses and protection induced by vectors that express the lack (leishmania-activated c-kinase antigen), alone or with insertion of the viral host range gene c7l that allows the virus to r ...	2016	27036935
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 ...	2016	26407073
proteomic analysis reveals differentially expressed proteins in macrophages infected with leishmania amazonensis or leishmania major.	cba macrophages effectively control leishmania major infection, yet are permissive to leishmania amazonensis. employing a transcriptomic approach, we previously showed the up-regulation of the genes involved in the classical pathway of macrophage activation in resistant mice. however, microarray analyses do not evaluate changes in gene expression that occur after translation. to circumvent this analytical limitation, we employed a proteomics approach to increase our understanding of the modulati ...	2016	23628411
chlorin e6 phototoxicity in l. major and l. braziliensis promastigotes-in vitro study.	cutaneous leishmaniasis is a zoonosis caused by protozoa of the genus leishmania. conventional treatments are long and aggressive, and they trigger a diversity of side effects. photodynamic therapy was originally proposed as a treatment for cancer, and it now appears to be a promising therapy for local treatment with fewer side effects of infectious diseases.	2016	27156802
in vitro evaluation of photodynamic therapy using curcumin on leishmania major and leishmania braziliensis.	cutaneous leishmaniasis is an infectious disease caused by the leishmania protozoan. the conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. this study investigated the photodynamic activity of curcumin on leishmania major and leishmania braziliensis promastigote. both species were submitted to incubation with curcumin in seri ...	2016	27056699
cross-protective efficacy of leishmania infantum lihyd protein against tegumentary leishmaniasis caused by leishmania major and leishmania braziliensis species.	vaccination can be considered the most cost-effective strategy to control neglected diseases, but nowadays there is not an effective vaccine available against leishmaniasis. in the present study, a vaccine based on the combination of the leishmania-specific hypothetical protein (lihyd) with saponin was tested in balb/c mice against infection caused by leishmania major and leishmania braziliensis species. this antigen was firstly identified in leishmania infantum and showed to be protective again ...	2016	26976272
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 ...	2016	26756314
chronic gastrointestinal nematode infection mutes immune responses to mycobacterial infection distal to the gut.	helminth infections have been suggested to impair the development and outcome of th1 responses to vaccines and intracellular microorganisms. however, there are limited data regarding the ability of intestinal nematodes to modulate th1 responses at sites distal to the gut. in this study, we have investigated the effect of the intestinal nematode heligmosomoides polygyrus bakeri on th1 responses to mycobacterium bovis bacillus calmette-guérin (bcg). we found that h. polygyrus infection localized t ...	2016	26819205
neutrophils contribute to the protection conferred by artinm against intracellular pathogens: a study on leishmania major.	artinm, a d-mannose binding lectin from artocarpus heterophyllus, has immunomodulatory activities through its interaction with n-glycans of immune cells, culminating with the establishment of t helper type 1 (th1) immunity. this interaction protects mice against intracellular pathogens, including leishmania major and leishmania amazonensis. artinm induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. although exacerbated inflammation w ...	2016	27058234
detection and molecular identification of leishmania rna virus (lrv) in iranian leishmania species.	leishmania rna virus (lrv) was first detected in members of the subgenus leishmania (viannia), and later, the virulence and metastasis of the new world species were attributed to this virus. the data on the presence of lrv in old world species are confined to leishmania major and a few leishmania aethiopica isolates. the aim of this study was to survey the presence of lrv in various iranian leishmania species originating from patients and animal reservoir hosts. genomic nucleic acids were extrac ...	2016	27604119