Publications

activity of anti-cancer protein kinase inhibitors against leishmania spp.	there is an urgent need to develop new and effective treatments for poverty-related neglected diseases. in light of the time required to bring a new drug to market and the cost involved (10-15 years, >1 billion us$), one approach to identifying new treatments for diseases like leishmaniasis is to evaluate drugs that are already registered for the treatment of other diseases. this paper describes the anti-leishmanial activities of 10 fda-approved protein kinase inhibitors already available for th ...	2014	24668412
in vitro and in vivo efficacy of novel flavonoid dimers against cutaneous leishmaniasis.	treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. we previously reported that synthetic flavonoid dimers have potent antipromastigote and antiamastigote activity against leishmania donovani, the causative agent of visceral leishmaniasis. here, we further investigate their leishmanicidal activities against cutaneous leishmania species. one of the flavonoid dimers (compound 39) has marked antipromastigote (50% inhib ...	2014	24687505
lc-ms metabolomics from study design to data-analysis - using a versatile pathogen as a test case.	thanks to significant improvements in lc-ms technology, metabolomics is increasingly used as a tool to discriminate the responses of organisms to various stimuli or drugs. in this minireview we discuss all aspects of the lc-ms metabolomics pipeline, using a complex and versatile model organism, leishmania donovani, as an illustrative example. the benefits of a hyphenated mass spectrometry platform and a detailed overview of the entire experimental pipeline from sampling, sample storage and sampl ...	2013	24688684
leishmanial lipid suppresses the bacterial endotoxin-induced inflammatory response with attenuation of tissue injury in sepsis.	the use of live, attenuated, or genetically modified microbes or their cellular component(s) or metabolites has begun to emerge as a potential new approach in medicinal research to deliver biologically active entities. thus, advancing our knowledge of such microbe-mediated therapy may suggest new avenues for therapeutic intervention in many diseases. we had earlier reported that the total lipid of attenuated leishmania donovani suppressed the inflammatory responses in rheumatoid arthritis patien ...	2014	24696356
no stress--hsp90 and signal transduction in leishmania.	summary hsp90 (a.k.a. hsp83) plays a significant role in the life cycle control of the protozoan parasite leishmania donovani. rather than protecting leishmania spp. against adverse and stressful environs, hsp90 is required for the maintenance of the motile, highly proliferative insect stage, the promastigote. however, hsp90 is also essential for survival and proliferation of the intracellular mammalian stage, the amastigote. moreover, recent evidence shows hsp90 and other components of large mu ...	2014	24703183
antiprotozoal activities of millettia richardiana (fabaceae) from madagascar.	with at least 60% of the millettia species (fabaceae) being in medicinal use, we found it relevant to assess the potential antiprotozoal and antifungal activities of millettia richardiana. water and methanol crude extracts of the stem barks from m. richardiana and the six fractions resulting from the fractionation of the methanol extract were tested. the dichloromethane extracted fraction showed the best in vitro antiprotozoal activities (ic50=5.8 μg/ml against plasmodium falciparum, 11.8 μg/ml ...	2014	24705564
flavone-resistant leishmania donovani overexpresses ldmrp2 transporter in the parasite and activates host mrp2 on macrophages to circumvent the flavone-mediated cell death.	in parasites, atp-binding cassette (abc) transporters represent an important family of proteins related to drug resistance and other biological activities. resistance of leishmanial parasites to therapeutic drugs continues to escalate in developing countries, and in many instances, it is due to overexpressed abc efflux pumps. progressively adapted baicalein (bln)-resistant parasites (pb(25)r) show overexpression of a novel abc transporter, which was classified as abcc2 or leishmania donovani mul ...	2014	24706751
[from unexplained fever to visceral leishmaniasis--a case report].	visceral leishmaniasis or kala-azar is a systemic infectious vector-borne disease caused by protozoa leishmania donovani and leishmania infantum that are transmitted to mammalian hosts by sand flies. it occurrs sporadically in endemic areas, including mediterranean basin. southern coastal territories of croatia have been recognized as the foci of the disease. dogs are the main reservoir of human infection. clinical features include prolonged fever, malaise, hepatosplenomegaly, pancytopenia and i ...	2014	24720151
design, synthesis, adme characterization and antileishmanial evaluation of novel substituted quinoline analogs.	in vitro adme characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. compound 1 was highly permeable in intestinal pampa model (31 × 10(-6)cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. compound 1 was found to have no cyp450 liability with cyp2c9, 2 ...	2014	24726804
ketanserin, an antidepressant, exerts its antileishmanial action via inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) enzyme of leishmania donovani.	leishmaniasis is one of the major health problems existing globally. the current chemotherapy for leishmaniasis presents several drawbacks like toxicity and increased resistance to existing drugs, and hence, there is a necessity to look out for the novel drug targets and new chemical entities. current trend in drug discovery arena is the "repurposing" of old drugs for the treatment of diseases. in the present study, an antidepressant, ketanserin, was found lethal to both leishmania donovani prom ...	2014	24728519
combination of liposomal cpg oligodeoxynucleotide 2006 and miltefosine induces strong cell-mediated immunity during experimental visceral leishmaniasis.	immuno-modulators in combination with antileishmanial drug miltefosine is a better therapeutic approach for treatment of visceral leishmaniasis (vl) as it not only reduces the dose of miltefosine but also shortens the treatment regimen. however, immunological mechanisms behind the perceived benefits of this combination therapy have not been investigated in detail. in the present study, we hypothesized that potential use of drugs that target the host in addition to the parasite might represent an ...	2014	24732039
evaluation of leishmania donovani disulfide isomerase as a potential target of cellular immunity against visceral leishmaniasis.	in leishmania species, protein disulfide isomerase (pdi) - a redox chaperone is primarily associated with virulence and survival. the precise mechanism, especially in relation to redox changes and its effects on immunological responses in visceral leishmaniasis (vl) is not completely understood as yet. therefore, we purified a recombinant pdi from leishmania donovani (r-ldpdi) which was of ∼15 kda molecular size and examined its effects on immunological responses in peripheral blood (pbmc) of hu ...	2014	24732062
regulation dynamics of leishmania differentiation: deconvoluting signals and identifying phosphorylation trends.	leishmania are obligatory intracellular parasitic protozoa that cause a wide range of diseases in humans, cycling between extracellular promastigotes in the mid-gut of sand flies and intracellular amastigotes in the phagolysosomes of mammalian macrophages. although many of the molecular mechanisms of development inside macrophages remain a mystery, the development of a host-free system that simulates phagolysosome conditions (37 °c and ph 5.5) has provided new insights into these processes. the ...	2014	24741111
concomitant infection with leishmania donovani and l. major in single ulcers of cutaneous leishmaniasis patients from sudan.	in sudan human leishmaniasis occurs in different clinical forms, that is, visceral (vl), cutaneous (cl), mucocutaneous (ml), and post-kala-azar dermal leishmaniasis (pkdl). clinical samples from 69 sudanese patients with different clinical manifestations were subjected to a pcr targeting the cytochrome oxidase ii (coii) gene for leishmania species identification. mixed infections were suspected due to multiple overlapping peaks presented in some sequences of the coii amplicons. cloning these amp ...	2014	24744788
a comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study.	visceral leishmaniasis (vl) represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. ninety per cent of vl cases occur in five countries namely bangladesh, india, nepal, sudan and brazil. no licensed vaccine is available till date against any form of leishmaniasis. high toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in vl endemic regions of the world. to ...	2014	24747611
kala-azar in a brazilian child.	we report the case of a six-year-old brazilian girl referred for splenomegaly who first presented with fever, asthenia, and weight loss. geographical location, clinical exam, and blood laboratories suggested kala-azar. serology confirmed kala-azar diagnosis, but direct evidence of the parasites was not made. a treatment by meglumine antimoniate is given under hospital surveillance for two weeks. thereupon, the patient is asymptomatic and all tests are normal.	2011	24765289
shagenes a and b, new tricyclic sesquiterpenes produced by an undescribed antarctic octocoral.	the isolation and characterization of two new tricyclic sesquiterpenoids, shagenes a (1) and b (2) are presented. these compounds were isolated from an undescribed soft coral collected from the scotia arc in the southern ocean. one- and two-dimensional nmr spectroscopy and mass spectrometry provided the data necessary to characterize the compounds and their relative stereochemical configurations. exploration of the bioactivity of shagenes a and b found 1 active against the visceral leishmaniasis ...	2014	24779517
integrity of the actin cytoskeleton of host macrophages is essential for leishmania donovani infection.	visceral leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoan parasite leishmania donovani. the molecular mechanism involved in internalization of leishmania is poorly understood. the entry of leishmania involves interaction with the plasma membrane of host cells. we have previously demonstrated the requirement of host membrane cholesterol in the binding and internalization of l. donovani into macrophages. in the present work, we explored the role of the host act ...	2014	24780377
trend analysis of visceral leishmaniasis at addis zemen health center, northwest ethiopia.	visceral leishmaniasis (vl) is a systemic disease caused by the leishmania donovani complex. it is one of the fatal diseases if left untreated. in ethiopia, there are many vl endemic foci. the aim of this study was to determine the trends of vl in the study area.	2014	24783211
4-amino bis-pyridinium derivatives as novel antileishmanial agents.	the antileishmanial activity of a series of bis-pyridinium derivatives that are analogues of pentamidine have been investigated, and all compounds assayed were found to display activity against promastigotes and intracellular amastigotes of leishmania donovani and leishmania major, with 50% effective concentrations (ec50s) lower than 1 μm in most cases. the majority of compounds showed similar behavior in both leishmania species, being slightly more active against l. major amastigotes. however, ...	2014	24798287
the leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status.	during its life cycle, the protozoan pathogen leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, to which the parasite must adapt for extra- and intracellular survival. combining null mutant analysis with phosphorylation site-specific mutagenesis and functional complementation we genetically tested the requirement of the l. donovani chaperone cyclophilin 40 (ldcyp40) for infection. targeted replacement of ldcyp40 had no effect on parasite viabili ...	2014	24811325
leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.	leishmaniasis is a neglected tropical disease caused by leishmania species. it is a major health concern affecting 88 countries and threatening 350 million people globally. unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. the emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. the genome sequence of leishmania, provides access to novel genes that hold pot ...	2014	24814525
deficiency of lymph node-resident dendritic cells (dcs) and dysregulation of dc chemoattractants in a malnourished mouse model of leishmania donovani infection.	malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan leishmania donovani. we previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination of l. donovani. in t ...	2014	24818662
cross-protective immunity to leishmania amazonensis is mediated by cd4+ and cd8+ epitopes of leishmania donovani nucleoside hydrolase terminal domains.	the nucleoside hydrolase (nh) of leishmania donovani (nh36) is a phylogenetic marker of high homology among leishmania parasites. in mice and dog vaccination, nh36 induces a cd4+ t cell-driven protective response against leishmania chagasi infection directed against its c-terminal domain (f3). the c-terminal and n-terminal domain vaccines also decreased the footpad lesion caused by leishmania amazonensis. we studied the basis of the crossed immune response using recombinant generated peptides co ...	2014	24822054
efficacy of withania somnifera chemotypes nmitli - 101r, 118r and withaferin a against experimental visceral leishmaniasis.	the immunoprophylactic and therapeutic potentials of root extracts of withania somnifera chemotypes (nmitli-118, nmitli-101) and pure withanolide-withaferin a was investigated against leishmania donovani infection in hamsters. the naive animals, fed orally with immunostimulatory doses of chemotypes 101r, 118r (10 and 3 mg/kg) and withaferin a (9 and 3 mg/kg) for five consecutive days and challenged with leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of p ...	2014	24830833
epidemiology of visceral leishmaniasis.	leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. these parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. this review focuses on the two parasites causing most human visceral leishmaniasis (vl), which leads to substantial health problems or death for up to 400,000 people per year. except for travel cases, leishmania donovani infections are restricted to the (sub-)tropics of ...	2014	24833919
generation of growth arrested leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.	visceral leishmaniasis (vl) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. vl is caused by the protozoan parasite leishmania donovani or leishmania infantum. although several second generation vaccines have been licensed to protect dogs against vl, there are no effective vaccines against human vl [1]. since people cured of leishmaniasis develop lifelong protection, development of live attenuated leishmania parasites as vaccines, which can have ...	2014	24837513
coating doxorubicin-loaded nanocapsules with alginate enhances therapeutic efficacy against leishmania in hamsters by inducing th1-type immune responses.	the aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(sa) coated nanocapsule (ncs) loaded with doxorubicin (sa-ncs-dox) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (ne-dox).	2014	24837879
tick-borne infections of animals and humans: a common ground.	a wide variety of pathogens is transmitted from ticks to vertebrates including viruses, bacteria, protozoa and helminths, of which most have a life cycle that requires passage through the vertebrate host. tick-borne infections of humans, farm and companion animals are essentially associated with wildlife animal reservoirs. while some flying insect-borne diseases of humans such as malaria, filariasis and kala azar caused by leishmania donovani target people as their main host, major tick-borne in ...	2014	24846527
class ii mhc/peptide interaction in leishmania donovani infection: implications in vaccine design.	we show that leishmania donovani-infected macrophages (mφs) are capable of stimulating mhc class ii (mhc-ii)-restricted t cells at 6 h of infection. at 48 h, infected mφs (i-mφs) failed to stimulate mhc-ii-restricted t cells but not mhc class i-restricted ones, in contrast to normal mφs. such i-mφs could stimulate t cells at a higher ag concentration, indicating that general ag processing and trafficking of peptide-mhc-ii complexes are not defective. analysis of the kinetic parameters, like "kon ...	2014	24850723
cutaneous leishmaniasis in north dakota.	in the united states, autochthonous cutaneous leishmaniasis caused by infection with leishmania mexicana has been reported from texas and oklahoma. here, we describe a child with 2 new features: cutaneous infection acquired outside of the south-central united states (in north dakota) and infection caused by leishmania donovani species complex.	2014	24850800
synthesis and biological evaluation of chalcones as potential antileishmanial agents.	antileishmanial activities of thirty-five synthetic chalcones have been examined. among them, ten compounds (4, 6, 16, 22, 23, 24, 25, 29, 35 and 37) exhibited potent in vitro activity (ic50 range from 1.70 to 8 μm) against extracellular promastigotes and intracellular amastigotes form of leishmania donovani. two promising compounds 22 and 37 were tested in vivo in l. donovani/hamster model. chalcone 37 showed 83.32% parasite inhibition at a dose of 50 mg/kg for 10 days whereas, 75.89% parasite ...	2014	24858541
antileishmanial activity of a series of n²,n⁴-disubstituted quinazoline-2,4-diamines.	a series of n(2),n(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against leishmania donovani and l. amazonensis intracellular amastigotes. a structure-activity and structure-property relationship study was conducted in part using the topliss operational scheme to identify new lead compounds. this study led to the identification of quinazolines with ec50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. q ...	2014	24874647
a dual luciferase system for analysis of post-transcriptional regulation of gene expression in leishmania.	gene expression in kinetoplastid parasites is regulated via post-transcriptional mechanisms that modulate mrna turnover, translation rate, and/or post-translational protein stability. to facilitate the analysis of post-transcriptional regulation, a dual luciferase system was developed in which firefly and renilla luciferase reporters genetically fused to compatible drug resistance genes are integrated in place of one allele of the gene of interest and of an internal control gene, respectively, i ...	2014	24878002
an inhibitor-driven study for enhancing the selectivity of indirubin derivatives towards leishmanial glycogen synthase kinase-3 over leishmanial cdc2-related protein kinase 3.	in search of new antiparasitic agents for overcoming the limitations of current leishmaniasis chemotherapy, we have previously shown that 6-bromoindirubin-3'-oxime (6bio) and several other 6-substituted analogues of indirubin, a naturally occurring bis-indole present in mollusks and plants, displayed reverse selectivity from the respective mammalian kinases, targeting more potently the leishmanial cyclin-dependent kinase-1 (cdk1) homologue [cdc2-related protein kinase 3 (lcrk3)] over leishmanial ...	2014	24886176
cytokine profiles amongst sudanese patients with visceral leishmaniasis and malaria co-infections.	the immune system plays a critical role in the development of co-infections, promoting or preventing establishment of multiple infections and shaping the outcome of pathogen-host interactions. its ability to mediate the interplay between visceral leishmaniasis (vl) and malaria has been suggested, but poorly documented. the present study investigated whether concomitant infection with leishmania donovani complex and plasmodium falciparum in naturally co-infected patients altered the immunological ...	2014	24886212
equilibrium unfolding of cyclophilin from leishmania donovani: characterization of intermediate states.	cyclophilin from leishmania donovani (ldcyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase involved in a host of important cellular activities, such as signaling, heat shock response, chaperone activity, mitochondrial pore maintenance and regulation of hiv-1 infectivity. it also acts as the prime cellular target for the auto-immune drug cyclosporine a (csa). ldcyp is composed of a beta barrel encompassing the unique hydrophobic core of the molecule and is flanked by two helices (h1, h2) on ...	2014	24887548
studies on the antileishmanial mechanism of action of the arylimidamide db766: azole interactions and role of cyp5122a1.	arylimidamides (aias) are inspired by diamidine antimicrobials but show superior activity against intracellular parasites. the aia db766 {2,5-bis[2-(2-i-propoxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride} displays outstanding potency against intracellular leishmania parasites and is effective in murine and hamster models of visceral leishmaniasis when given orally, but its mechanism of action is unknown. in this study, through the use of continuous db766 pressure, we raised leishmania do ...	2014	24890590
hplc-based activity profiling for antiplasmodial compounds in the traditional indonesian medicinal plant carica papaya l.	leaf decoctions of carica papaya have been traditionally used in some parts of indonesia to treat and prevent malaria. leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo.	2014	24892830
stage-dependent expression and up-regulation of trypanothione synthetase in amphotericin b resistant leishmania donovani.	kinetoplastids differ from other organisms in their ability to conjugate glutathione and spermidine to form trypanothione which is involved in maintaining redox homeostasis and removal of toxic metabolites. it is also involved in drug resistance, antioxidant mechanism, and defense against cellular oxidants. trypanothione synthetase (trys) of thiol metabolic pathway is the sole enzyme responsible for the biosynthesis of trypanothione in leishmania donovani. in this study, trys gene of l. donovani ...	2014	24901644
biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.	despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. a major shortcoming in the vaccine development against blood-borne parasitic agents such as leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extr ...	2014	24904589
chemical- and thermal-induced unfolding of leishmania donovani ribose-5-phosphate isomerase b: a single-tryptophan protein.	ribose-5-phosphate isomerase b (rpib), a crucial enzyme of pentose phosphate pathway, was proposed to be a potential drug target for visceral leishmaniasis. in this study, we have analyzed the biophysical properties of leishmania donovani rpib (ldrpib) enzyme to gain insight into its unfolding pathway under various chemical and thermal denaturation conditions by using fluorescence and cd spectroscopy. ldrpib inactivation precedes the structural transition at lower concentrations of both urea and ...	2014	24907042
ubiquitination-mediated interaction among domains is responsible for inhibition of rna endonuclease activity of mrna cycling sequence binding protein from l. donovani (ldcsbp).	in nearly complete absence of transcriptional regulation, messenger rna (mrna) turnover mediated through specific cis-elements plays a predominant role in the control of differential gene expression for the disease causing trypanosomatid parasites. in these organisms, the periodic accumulation of s-phase messages during cell cycle is determined by the presence of one or more copies of a conserved cauagaag octanucleotide motif in the untranslated regions of mrnas. in our previous studies, a multi ...	2014	24908431
leishmania donovani eukaryotic initiation factor 5a: molecular characterization, localization and homology modelling studies.	eukaryotic translation initiation factor 5a (eif5a) is a small acidic protein highly conserved from archaea to mammals. eif5a is the only protein which undergoes a unique lysine residue modification to hypusine. hypusinylation is important for the function of eif5a which is reported to be essential for cell viability. eif5a promotes formation of the first peptide bond at the onset of protein synthesis. however, its function in leishmania donovani is unclear. the present study focuses on the char ...	2014	24909104
atypical cutaneous leishmaniasis in the immunosuppressed.	a 45-year-old woman, known case of seronegative arthritis and on immunosuppressive therapy, presented with a 2-week history of a macular lesion on the left calf that became papular and eventually ulcerated. the rest of the history was otherwise unremarkable and systemic examination did not reveal any abnormalities. the lesion was repeatedly biopsied but failed to reveal leishmania donovani bodies. concurrent leishmania igg was positive but igm was negative. leishmania igg confirmatory testing by ...	2014	24916985
antigen-pulsed cpg-odn-activated dendritic cells induce host-protective immune response by regulating the t regulatory cell functioning in leishmania donovani-infected mice: critical role of cxcl10.	visceral leishmaniasis (vl), caused by leishmania donovani, is a systemic infection of reticulo-endothelial system. there is currently no protective vaccine against vl and chemotherapy is increasingly limited due to appearance of drug resistance to first line drugs such as antimonials and amphotericin b. in the present study, by using a murine model of leishmaniasis we evaluated the function played by soluble leishmanial antigen (sla)-pulsed cpg-odn-stimulated dendritic cells (sla-cpg-dcs) in re ...	2014	24926293
nucleosomal histone proteins of l. donovani: a combination of recombinant h2a, h2b, h3 and h4 proteins were highly immunogenic and offered optimum prophylactic efficacy against leishmania challenge in hamsters.	the present study includes cloning and expression of recombinant leishmania donovani histone proteins (rldh2b, rldh3, rldh2a and rldh4), assessment of their immunogenicity in leishmania infected cured patients/endemic contacts as well as in cured hamsters and finally evaluation of their prophylactic efficacy in hamsters against l. donovani challenge. all recombinant proteins were expressed and purified from the heterologous bacterial host system. leishmania infected cured patients/endemic contac ...	2014	24926878
molecular docking and in vitro antileishmanial evaluation of chromene-2-thione analogues.	leishmaniases are an epidemic in various countries, and the parasite is developing resistance against available drugs. thus, development of new drugs against leishmania is an open area of investigation for synthetic organic chemists. to meet this challenge, a series of chromene-2-thione derivatives have been synthesized and docked into the active site of trypanothione reductase (tryr) enzyme required for redox balance of the parasite. these were screened on promastigote, axenic amastigote, and i ...	2012	24936236
nerve growth factor promotes killing of leishmania donovani by macrophages through the induction of hydrogen peroxide.	visceral leishmaniasis is protozoonosis that occurs worldwide and still requires effective therapies with less toxicity. in this study, we examined the antileishmanial effect of nerve growth factor (ngf) using a murine infection model. ngf blocked the infection of macrophages by leishmania donovani, which was completely cancelled by a hydrogen peroxide inhibitor. in vivo, not only did ngf show antileishmanial effects, but combination therapy of ngf and sodium stibogluconate synergistically exhib ...	2014	24937592
ornithine decarboxylase of leishmania donovani: biochemical properties and possible role of n-terminal extension.	leishmaniasis is a wide spread tropical disease caused by protozoan parasite leishmania which belongs to order kinetoplastida and family trypanosomatidae. ornithine decarboxylase is key enzyme in polyamine biosynthesis in leishmania donovani. here, we report biochemical characterization of ornithine decarboxylase from l. donovani. furthermore, we have also investigated the role of n-terminal extension (250 amino acids) found in ornithine decarboxylase of l. donovani (ldodc). the removal of n-ter ...	2015	24939662
clinical and parasitological protection in a leishmania infantum-macaque model vaccinated with adenovirus and the recombinant a2 antigen.	visceral leishmaniasis (vl) is a severe vector-born disease of humans and dogs caused by leishmania donovani complex parasites. approximately 0.2 to 0.4 million new human vl cases occur annually worldwide. in the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. thus, a prophylactic vaccine appears to be essential for vl control. the current efforts to develop an efficacious vaccine include the use o ...	2014	24945284
deficiency of p110δ isoform of the phosphoinositide 3 kinase leads to enhanced resistance to leishmania donovani.	visceral leishmaniasis is the most clinically relevant and dangerous form of human leishmaniasis. most traditional drugs for treatment of leishmaniasis are toxic, possess many adverse reactions and drug resistance is emerging. therefore, there is urgent need for identification of new therapeutic targets. recently, we found that mice with an inactivating knock-in mutation in the p110δ isoform of pi3k, (p110δ(d910a)) are hyper resistant to l. major, develop minimal cutaneous lesion and rapidly cle ...	2014	24945303
mianserin, an antidepressant kills leishmania donovani by depleting ergosterol levels.	in the present study, we have investigated the antileishmanial potential of mianserin, an antidepressant. mianserin was found to inhibit both the promastigote and amastigote forms of the parasite in a dose dependant manner. the ic50 values for promastigotes and amastigotes were 21 μm and 46 μm respectively. interestingly, mianserin failed to inhibit thp-1 differentiated macrophages up to 100 μm concentration thus, exhibiting parasite selectivity. when mianserin was incubated with recombinant lei ...	2014	24950381
leishmania spp. proteome data sets: a comprehensive resource for vaccine development to target visceral leishmaniasis.	visceral leishmaniasis is a neglected infectious disease caused primarily by leishmania donovani and leishmania infantum protozoan parasites. a significant number of infections take a fatal course. drug therapy is available but still costly and parasites resistant to first line drugs are observed. despite many years of trial no commercial vaccine is available to date. however, development of a cost effective, needle-independent vaccine remains a high priority. reverse vaccinology has attracted m ...	2014	24959165
leishmania donovani nucleoside hydrolase terminal domains in cross-protective immunotherapy against leishmania amazonensis murine infection.	nucleoside hydrolases of the leishmania genus are vital enzymes for the replication of the dna and conserved phylogenetic markers of the parasites. leishmania donovani nucleoside hydrolase (nh36) induced a main cd4(+) t cell driven protective response against l. chagasi infection in mice which is directed against its c-terminal domain. in this study, we used the three recombinant domains of nh36: n-terminal domain (f1, amino acids 1-103), central domain (f2 aminoacids 104-198), and c-terminal do ...	2014	24966857
growth factor and th2 cytokine signaling pathways converge at stat6 to promote arginase expression in progressive experimental visceral leishmaniasis.	host arginase 1 (arg1) expression is a significant contributor to the pathogenesis of progressive visceral leishmaniasis (vl), a neglected tropical disease caused by the intracellular protozoan leishmania donovani. previously we found that parasite-induced arg1 expression in macrophages was dependent on stat6 activation. arg1 expression was amplified by, but did not require, il-4, and required de novo synthesis of unknown protein(s). to further explore the mechanisms involved in arg1 regulation ...	2014	24967908
synthesis, antileishmanial and antitrypanosomal activities of n-substituted tetrahydro-β-carbolines.	a series of n-substituted tetrahydro-β-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of leishmania donovani, the causative agent for visceral leishmaniasis. the thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with ic50 values of 12.7, 9.1 and 22.1 μm, respectively. analogs 9b and 11h were also effective against axenic amastigo ...	2014	24980054
immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease.	self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; visceral leishmaniasis (vl), which is fatal if left untreated. the epidemiology and clinical features of vl vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. human immunodeficiency virus infection augments the severity of vl increasing the risk of developing active disease by 100-2320 times. an effective vacc ...	2014	24982655
genetic analysis of leishmania donovani tropism using a naturally attenuated cutaneous strain.	a central question in leishmania research is why most species cause cutaneous infections but others cause fatal visceral disease. interestingly, l. donovani causes both visceral and cutaneous leishmaniasis in sri lanka. l. donovani clinical isolates were therefore obtained from cutaneous leishmaniasis (cl-sl) and visceral leishmaniasis (vl-sl) patients from sri lanka. the cl-sl isolate was severely attenuated compared to the vl-sl isolate for survival in visceral organs in balb/c mice. genomic a ...	2014	24992200
multilocus sequence and microsatellite identification of intra-specific hybrids and ancestor-like donors among natural ethiopian isolates of leishmania donovani.	protozoan parasites of the genus leishmania (kinetoplastida: trypanosomatidae) cause widespread and devastating human diseases. visceral leishmaniasis is endemic in ethiopia where it has also been responsible for fatal epidemics. it is postulated that genetic exchange in leishmania has implications for heterosis (hybrid vigour), spread of virulent strains, resistance to chemotherapeutics, and exploitation of different hosts and vectors. here we analyse 11 natural ethiopian leishmania donovani is ...	2014	24995620
parasite load estimation by qpcr differentiates between asymptomatic and symptomatic infection in indian visceral leishmaniasis.	using quantitative pcr (qpcr), we differentiated asymptomatic and symptomatic indian leishmania donovani infection. qpcr on blood of 40 visceral leishmaniasis, 130 endemic, and 40 non-endemic healthy controls showed 500 times less (p < .0001) parasitemia in asymptomatic compared to the symptomatic ones and threshold of 5 parasite genome/ml for the clinical disease.	2014	25023070
antimony resistant leishmania donovani but not sensitive ones drives greater frequency of potent t-regulatory cells upon interaction with human pbmcs: role of il-10 and tgf-β in early immune response.	in india the sand fly, phlebotomus argentipes, transmitted parasitic disease termed kala-azar is caused by leishmania donovani (ld) in humans. these immune-evading parasites have increasingly developed resistance to the drug sodium antimony gluconate in endemic regions. lack of early diagnosis methods for the disease limits the information available regarding the early interactions of this parasite with either human tissues or cell lineages. we reasoned that peripheral blood mononuclear cells (p ...	2014	25032977
in vitro and in vivo miltefosine susceptibility of a leishmania amazonensis isolate from a patient with diffuse cutaneous leishmaniasis.	miltefosine was the first oral compound approved for visceral leishmaniasis chemotherapy, and its efficacy against leishmania donovani has been well documented. leishmania amazonensis is the second most prevalent species causing cutaneous leishmaniasis and the main etiological agent of diffuse cutaneous leishmaniasis in brazil. driven by the necessity of finding alternative therapeutic strategies for a chronic diffuse cutaneous leishmaniasis patient, we evaluated the susceptibility to miltefosin ...	2014	25033218
synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against leishmania donovani and trypanosoma cruzi.	a high-throughput (hts) and high-content screening (hcs) campaign of a commercial library identified 2,3-dihydroimidazo[1,2-a]benzimidazole analogues as a novel class of anti-parasitic agents. a series of synthetic derivatives were evaluated for their in vitro anti-leishmanial and anti-trypanosomal activities against leishmania donovani and trypanosoma cruzi, which have been known as the causative parasites for visceral leishmaniasis and chagas disease, respectively. in the case of leishmania, t ...	2014	25036797
a case of mucocutaneous leishmaniasis diagnosed by serology.	a 43-year-old japanese bolivian male had been suffering from a right leg ulcer after an insect bite during his residence in bolivia. the ulcer healed after herbal medicine treatment. ten years later, the patient had symptoms of nasal obstruction, nasal bleeding, and pharyngodynia, which were accompanied by a destructive ulcer with surrounding erythema involving the right nostril apex and columella. papillary, irregular mucosal lesions were seen on the soft palate. giemsa staining and polymerase ...	2014	25041360
the isolation of antiprotozoal compounds from libyan propolis.	propolis is increasingly being explored as a source of biologically active compounds. until now, there has been no study of libyan propolis. two samples were collected in north east libya and tested for their activity against trypanosoma brucei. extracts from both samples had quite high activity. one of the samples was fractionated and yielded a number of active fractions. three of the active fractions contained single compounds, which were found to be 13-epitorulosal, acetyl-13-epi-cupressic ac ...	2014	25044090
prostaglandin e2 negatively regulates the production of inflammatory cytokines/chemokines and il-17 in visceral leishmaniasis.	persistence of intracellular infection depends on the exploitation of factors that negatively regulate the host immune response. in this study, we elucidated the role of macrophage pge2, an immunoregulatory lipid, in successful survival of leishmania donovani, causative agent of the fatal visceral leishmaniasis. pge2 production was induced during infection and resulted in increased camp level in peritoneal macrophages through g protein-coupled e-series prostanoid (ep) receptors. among four diffe ...	2014	25049356
retraction. anti-citrullinated peptide antibodies and rheumatoid factor in sudanese patients with leishmania donovani infection.		2014	25054607
how often do they have sex? a comparative analysis of the population structure of seven eukaryotic microbial pathogens.	the model of predominant clonal evolution (pce) proposed for micropathogens does not state that genetic exchange is totally absent, but rather, that it is too rare to break the prevalent pce pattern. however, the actual impact of this "residual" genetic exchange should be evaluated. multilocus sequence typing (mlst) is an excellent tool to explore the problem. here, we compared online available mlst datasets for seven eukaryotic microbial pathogens: trypanosoma cruzi, the fusarium solani complex ...	2014	25054834
isolated cutaneous leishmaniasis by leishmania donovani in a soldier returning from afghanistan.		2015	25062262
reactive oxygen species regulates expression of iron-sulfur cluster assembly protein iscs of leishmania donovani.	the cysteine desulfurase, iscs, is a highly conserved and essential component of the mitochondrial iron-sulfur cluster (isc) system that serves as a sulfur donor for fe-s clusters biogenesis. fe-s clusters are versatile and labile cofactors of proteins that orchestrate a wide array of essential metabolic processes, such as energy generation and ribosome biogenesis. however, no information regarding the role of iscs or its regulation is available in leishmania, an evolving pathogen model with rap ...	2014	25062827
induction of mitochondrial dysfunction and oxidative stress in leishmania donovani by orally active clerodane diterpene.	this study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (k-09) in leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (vl). k-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in l. donovani promastigotes. mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the ...	2014	25070112
diverse modes of binding in structures of leishmania major n-myristoyltransferase with selective inhibitors.	the leishmaniases are a spectrum of global diseases of poverty associated with immune dysfunction and are the cause of high morbidity. despite the long history of these diseases, no effective vaccine is available and the currently used drugs are variously compromised by moderate efficacy, complex side effects and the emergence of resistance. it is therefore widely accepted that new therapies are needed. n-myristoyltransferase (nmt) has been validated pre-clinically as a target for the treatment ...	2014	25075346
serological surveillance development for tropical infectious diseases using simultaneous microsphere-based multiplex assays and finite mixture models.	a strategy to combat infectious diseases, including neglected tropical diseases (ntds), will depend on the development of reliable epidemiological surveillance methods. to establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in kenya.	2014	25078404
protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from withania somnifera and asparagus racemosus.	visceral leishmaniasis (vl) is a vector-borne parasitic disease targeting tissue macrophages. it is among the most neglected infectious diseases. as available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. one of the immunopathological consequences of active visceral leishmaniasis is suppression of protective t-helper (th)-1 cells and induction of disease-promoting th-2 cells, and thus the treatment of vl relies on immunomodulation. in ...	2014	25082945
antileishmanial metabolites from geosmithia langdonii.	antileishmanial bioassay guided fractionation of geosmithia langdonii has resulted in the isolation and identification of two new compounds (1 and 2) together with 10 known compounds (3-12). the structures of the isolated metabolites were elucidated based on comprehensive 1d and 2d nmr spectroscopic data as well as mass spectrometry. the absolute configuration at c4, c5, and c6 of 2 was determined as r using a modified mosher esterification method and noesy correlations. the extracts and the iso ...	2014	25084548
carbon nanotube based betulin formulation shows better efficacy against leishmania parasite.	we report a novel antileishmanial formulation of betulin (bet) attached to functionalized carbon nanotubes (f-cnts). we conjugated betulin, a pentacyclic triterpenoid secondary metabolite, to carboxylic acid chains on f-cnts to obtain bet attached functionalized carbon nanotubes (f-cnt-bet). the drug release profile demonstrated a fairly slow release of bet. the in-vitro cytotoxicities of bet, f-cnt and f-cnt-bet on j774a.1 macrophage cell line were 211.05±7.14μg/ml; 24.67±3.11μg/ml and 72.63±6. ...	2014	25086374
a new approach for the delivery of artemisinin: formulation, characterization, and ex-vivo antileishmanial studies.	artemisinin, a potential antileishmanial compound with poor bioavailability and stability has limited efficacy in visceral leishmaniasis. encapsulating artemisinin into poly lactic-co glycolic nanoparticles may improve its effectiveness and reduce toxicity.	2014	25086720
a screen-and-treat strategy targeting visceral leishmaniasis in hiv-infected individuals in endemic east african countries: the way forward?	in the wake of the hiv epidemic, visceral leishmaniasis (vl), a disseminated protozoan infection caused by the leishmania donovani complex, has been re-emerging, particularly in north ethiopia where up to 40% of patients with vl are co-infected with hiv. management of vl in hiv co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. tackling l. donovani infection befor ...	2014	25101627
characterization of mitochondrial bioenergetic functions between two forms of leishmania donovani - a comparative analysis.	leishmaniasis is a growing health problem in many parts of the world partly due to drug resistance of the parasite. this study reports on the fisibility of studying mitochondrial properties of two forms of wild-type l. donovani through the use of selective inhibitors. amastigote forms of l. donovani exhibited a wide range of sensitivities to these inhibitors. mitochondrial complex ii inhibitor thenoyltrifluoroacetone and fof1-atp synthase inhibitors oligomycin and dicyclohexylcarbodiimide were r ...	2014	25107348
ascorbate peroxidase, a key molecule regulating amphotericin b resistance in clinical isolates of leishmania donovani.	amphotericin b (amb), a polyene macrolide, is now a first-line treatment of visceral leishmaniasis cases refractory to antimonials in india. amb relapse cases and the emergence of secondary resistance have now been reported. to understand the mechanism of amb, differentially expressed genes in amb resistance strains were identified by a dna microarray and real-time reverse transcriptase pcr (rt-pcr) approach. of the many genes functionally overexpressed in the presence of amb, the ascorbate pero ...	2014	25114128
lipid isolated from a leishmania donovani strain reduces escherichia coli induced sepsis in mice through inhibition of inflammatory responses.	sepsis is the reflection of systemic immune response that manifests in the sequential inflammatory process in presence of infection. this may occur as a result of gram-negative bacterial sepsis including escherichia coli infection that gives rise to excessive production of inflammatory mediators and causes severe tissue injuries. we have reported earlier that the lipid of attenuated leishmania donovani suppresses the inflammatory responses in arthritis patients. using heat killed e. coli stimula ...	2014	25120287
in vitro anti-leishmanial efficacy of potato tuber extract (ptex): leishmanial serine protease(s) as putative target.	leishmaniasis, a neglected tropical disease (ntd) causes major health problems in the tropical and subtropical world. most of the antileishmanial modern therapies with different formulations of pentavalent antimonials, miltefosine, amphotericin b etc. are not satisfactory in recent times due to high toxicity to the host and present rising strain resistance issues. so there is an urgent need to develop new, safe and cost-effective drugs against leishmaniasis. in this regard, bioactive phytocompon ...	2014	25128800
combining cationic liposomal delivery with mpl-tdm for cysteine protease cocktail vaccination against leishmania donovani: evidence for antigen synergy and protection.	with the paucity of new drugs and hiv co-infection, vaccination remains an unmet research priority to combat visceral leishmaniasis (vl) requiring strong cellular immunity. protein vaccination often suffers from low immunogenicity and poor generation of memory t cells for long-lasting protection. cysteine proteases (cps) are immunogenic proteins and key mediators of cellular functions in leishmania. here, we evaluated the vaccine efficacies of cps against vl, using cationic liposomes with toll l ...	2014	25144181
characterization of cross-protection by genetically modified live-attenuated leishmania donovani parasites against leishmania mexicana.	previously, we showed that genetically modified live-attenuated leishmania donovani parasite cell lines (ldcen(-/-) and ldp27(-/-)) induce a strong cellular immunity and provide protection against visceral leishmaniasis in mice. in this study, we explored the mechanism of cross-protection against cutaneous lesion-causing leishmania mexicana. upon challenge with wild-type l. mexicana, mice immunized either for short or long periods showed significant protection. immunohistochemical analysis of ea ...	2014	25156362
immunity to visceral leishmaniasis: implications for immunotherapy.	visceral leishmaniasis, caused by leishmania donovani, l. infantum (syn. leishmania chagasi), is a globally widespread disease with a burden of about 400,000 new infections reported annually. it is the most dangerous form of human leishmaniasis in terms of mortality and morbidity and is spreading to several nonendemic areas because of migration, global traveling and military conflicts. the emergence of leishmania-hiv co-infection and increased prevalence of drug-resistant strains have worsened t ...	2014	25156379
reduction of leishmania donovani infectivity in whole blood using riboflavin and ultraviolet light.	leishmaniasis is a vector-borne disease caused by the protozoan parasite leishmania sp. that is transmitted by sandflies. travelers to endemic areas, and us military personnel stationed in the middle east, are at risk for contracting the disease.	2015	25156473
comparison of pcr with stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis.	visceral leishmaniasis (vl), also known as kala-azar, is a disseminated protozoan infection caused by leishmania donovani complex. traditionally the definite diagnosis is made by amastigote detection in the tissue. the aim this study was to evaluate the pcr technique in stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis. slides were selected totaling 62 suspect cases (33 bone marrow samples and 29 lymph node samples) and 17 positive cases (8 bone mar ...	2014	25159534
coibanoles, a new class of meroterpenoids produced by pycnoporus sanguineus.	three new terpenoids of mixed biosynthetic origin were isolated from the culture filtrate of the endophytic fungus pycnoporus sanguineus. their structures were determined by extensive spectroscopic analyses. we have named these tricyclic and tetracyclic metabolites 'coibanoles a-c' in reference to coiba island and coiba national park, panamá, from which the plant and endophyte were collected. the extract was inactive to the human parasites trypanosoma cruzi, leishmania donovani, and plasmodium f ...	2012	25177062
a small heat shock protein is essential for thermotolerance and intracellular survival of leishmania donovani.	leishmania parasites must survive and proliferate in two vastly different environments - the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. the change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. although the functions of the main heat shock protein fami ...	2014	25179594
immunotherapy and targeted therapies in treatment of visceral leishmaniasis: current status and future prospects.	visceral leishmaniasis (vl) is a vector-borne chronic infectious disease caused by the protozoan parasite leishmania donovani or leishmania infantum. vl is a serious public health problem, causing high morbidity and mortality in the developing world with an estimated 0.2-0.4 million new cases each year. in the absence of a vaccine, chemotherapy remains the favored option for disease control, but is limited by a narrow therapeutic index, significant toxicities, and frequently acquired resistance. ...	2014	25183962
exposure to phlebotomus argentipes (diptera, psychodidae, phlebotominae) sand flies in rural areas of bihar, india: the role of housing conditions.	visceral leishmaniasis (vl) is a vector-borne infectious disease, caused by the protozoan leishmania donovani, which is transmitted by phlebotomine sand flies. in an earlier study in bihar, india, we found an association between incidence of vl and housing conditions. in the current study we investigated the influence of housing structure and conditions in and around the house on the indoor abundance of phlebotomus argentipes, the vector of vl in this area.	2014	25184542
sitamaquine-resistance in leishmania donovani affects drug accumulation and lipid metabolism.	this study focuses on the mechanism of sitamaquine-resistance in leishmania donovani. sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (wt) and of sitamaquine-resistant (sita-r160) l. donovani promastigotes, respectively. the sitamaquine accumulation was a concentration-dependent process in wt whereas a saturation occurred in sita-r160 suggesting a reduced uptake or an increase of the sitamaquine efflux. membrane negative phospholipids being the main target ...	2014	25201056
insilico analysis of hypothetical proteins unveils putative metabolic pathways and essential genes in leishmania donovani.	leishmaniasis is a parasitic disease caused by the protozoan leishmania, which is active in two broad forms namely, visceral leishmaniasis (vl or kala azar) and cutaneous leishmaniasis (cl). the disease is most prevalent in the tropical regions and poses a threat to over 70 countries across the globe. about 200 million people are estimated to be at risk of developing vl in the indian subcontinent, and this refers to around 67% of the global vl disease burden. the indian state of bihar alone acco ...	2014	25206363
imipramine exploits histone deacetylase 11 to increase the il-12/il-10 ratio in macrophages infected with antimony-resistant leishmania donovani and clears organ parasites in experimental infection.	the efflux of antimony through multidrug resistance protein (mdr)-1 is the key factor in the failure of metalloid treatment in kala-azar patients infected with antimony-resistant leishmania donovani (sb(r)ld). previously we showed that mdr-1 upregulation in sb(r)ld infection is il-10-dependent. imipramine, a drug in use for the treatment of depression and nocturnal enuresis in children, inhibits il-10 production from sb(r)ld-infected macrophages (sb(r)ld-mϕs) and favors accumulation of surrogate ...	2014	25217162
leishmania donovani activates srebp2 to modulate macrophage membrane cholesterol and mitochondrial oxidants for establishment of infection.	establishment of infection by an intracellular pathogen depends on successful internalization with a concomitant neutralization of host defense machinery. leishmania donovani, an intramacrophage pathogen, targets host srebp2, a critical transcription factor, to regulate macrophage plasma membrane cholesterol and mitochondrial reactive oxygen species generation, favoring parasite invasion and persistence. leishmania infection triggered membrane-raft reorientation-dependent lyn-pi3k/akt pathway ac ...	2014	25218172
tlr mediated gsk3β activation suppresses creb mediated il-10 production to induce a protective immune response against murine visceral leishmaniasis.	during leishmania donovani (ld) infection interleukin (il)-10 favors parasite replication and plays a central role as a target for immune-based therapy. glycogen synthase kinase 3 (gsk3)β differentially regulates tlr-mediated cytokine production. creb, an important transcription factor that induces il-10 production is negatively regulated by gsk3β. however, down regulation of il-10 via creb suppression has not been well explored in controlling ld infection. here we demonstrate that, the tlr4 ago ...	2014	25223889
leishmania donovani phosphoproteins pp41 and pp29 re-establishes host protective immune response in visceral leishmaniasis.	as phospho proteins are reported to be involved in virulence and survival, the ability of leishmania to inhibit macrophage effector functions may result from a direct interference of leishmanial molecules with macrophage signal transduction pathways. several such proteins such as pp63, pp41 and pp29 have also been identified as a th1 stimulatory protein in the leishmania donovani. in the present study, the immunogenicity of a cocktail of pp63+pp41+pp29 was assessed by estimation of serum antibod ...	2015	25224164
an imported case of cutaneous leishmaniasis caused by leishmania (leishmania) donovani in japan.	leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. there have been few reports of leishmaniasis in japan and all were of foreign origin; therefore diagnosis is difficult for japanese physicians. there are 21 different pathogenic leishmania species, and identification is obtained by polymerase chain reaction (pcr). here we report an imported case of leishmaniasis by leishmania (leishmania) donovani infection from sri lanka. l. (l.) d ...	2014	25228325
structure-based design of potent and selective leishmania n-myristoyltransferase inhibitors.	inhibitors of leishmania n-myristoyltransferase (nmt), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. crystal structures bound to leishmania major nmt were obtained, and the active diastereoisomer of one of the inhibitors was identified. on the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent leishmani ...	2014	25238611