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Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine
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With the World Health Organization reporting over 30,000 deaths and 200,000 to 400,000 new cases annually, visceral leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for leishmaniasis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new and more successful treatments for leishmaniasis. A novel method has been devised to study the metabolome and lipidome ofLeishmania donovaniaxenic amastigotes treated with miltefosine. Miltefosine caused a dramatic decrease in many membrane phospholipids (PLs), in addition to amino acid pools, while sphingolipids (SLs) and sterols increased.Leishmania majorpromastigotes devoid of SL biosynthesis through loss of the serine palmitoyl transferase gene (ΔLCB2) were 3-fold less sensitive to miltefosine than wild-type (WT) parasites. Changes in the metabolome and lipidome of miltefosine-treatedL. majormirrored those ofL. donovani. A lack of SLs in the ΔLCB2 mutant was matched by substantial alterations in sterol content. Together, these data indicate that SLs and ergosterol are important for miltefosine sensitivity and, perhaps, MoA.

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Publication Date
Sun Jan 01 2023
Journal Name
Aip Conference Proceedings
Ni2O3 nanomaterial: Synthesis and characterization by simple chemical process
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Publication Date
Sat Sep 01 2018
Journal Name
International Journal Of Applied Pharmaceutics
PREPARATION AND CHARACTERIZATION OF ECONAZOLE NITRATE INCLUSION COMPLEX FOR OCULAR DELIVERY SYSTEM
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Objective: Econazole nitrate (ECZ) is one of the triazole antifungal drugs with poor aqueous solubility and dissolution rate; there is a need for enhancement of solubility. Therefore; inclusion complexation with β cyclodextrin (βCD) was performed. Methods: In this study kneading method and co-evaporation method of preparation of inclusion complex between βCD and ECZ using two molar ratios of βCD. The solubility of these complexes in isotonic saline solution and distilled water was studied. Complexes prepared by kneading method were used for the preparation of different ophthalmic gel formulas using carbomer (CB) and sodium carboxymethylcellulose (sod CMC) as a gelling agent. The release profile and the rheological behaviour of the gel w

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Scopus
Publication Date
Fri Jun 20 2025
Journal Name
Sport Culture
Some bio-motor abilities and their relationship to the skill of standing on the hands followed by the forward roll on the mat of floor movements in artistic gymnastics for women
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The research consists of five chapters, and in the first chapter, it addresses the introduction and importance of the research, where the researcher explained the importance of bio-motor abilities and their role in achieving a high level through their connection to the skill performance of standing on the hands followed by the forward roll, and the research problem: Do these bio-motor abilities have an impact on the level of skill performance? Handstand followed by forward roll.

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Publication Date
Thu Jun 29 2023
Journal Name
Farmacia
CORRELATION BETWEEN INTEGRIN ALPHA-4 GENE POLYMORPHISMS AND FAILURE TO RESPOND TO NATALIZUMAB THERAPY IN IRAQI MULTIPLE SCLEROSIS PATIENTS
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Publication Date
Sun Jun 01 2014
Journal Name
International Journal Of Biological & Pharmaceutical Research
PROMASTIGOTES VIABILITY OF LEISHMANIA MAJOR W.T. ANDL. MAJOR KNOCKOUT LMLCB2 AFTER MYRIOCIN TREATMENT
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Sphingolipids (SLs) are major structural constituents of eukaryotes, including the kinetoplastid parasite Leishmania. SLs are important for cellular trafficking and signaling and participate in different cell functions, such as, differentiation and cell death (apoptosis). In this study we have investigated the viability of Leishmania major wild type (W.T) and L. major knockout LmLCB2, one of two subunits of serine palmitoyl transferase (SPT) after treatment with myriocin (potent inhibitor of SPT) in order to detect the survival and proliferation of the parasites in vitro. This is to focus on the de novo sphingolipids biosynthesis pathway in both Leishmania wild type which can synthesize SPT and knockout Leishmania which genetically ablated

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Publication Date
Fri Jun 20 2025
Journal Name
Research Journal Of Pharmacy And Technology
Ex vivo study of anti-leishmanial activity of artemisinin against Leishmania tropica amastigote
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Leishmania parasites are the causative agent of leishmaniasis. Many studies are inspecting chemical drugs, including the use of miltefosine and amphotericin B, but curative values may be limited for these drugs with side effects due to the chemical origin, therefore, investigating less toxic therapies is essential. The aim of this study was to investigate the effectiveness of artemisinin on Iraqi strain of Leishmania tropica, by experimental macrophage ex vivo infection of amastigotes into mouse macrophage cell-line RAW264.7. Different concentrations (100, 200, 300, 400, 500)μM of artemisinin (ART) were screened to examine the susceptibility of L. tropica amastigotes to invade macrophage cell line along three times of follow up (24, 48 and

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Publication Date
Wed Jul 24 2024
Journal Name
Annals Of Parasitology
In vitro efficacy of different concentrations of lupeol on old world Leishmania donovani
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Leishmaniosis is a tropical neglected parasitic disease that is endemic in many countries, including Middle East, with no existing effective vaccines. The bite of female sand-fly transmits the causative agent, Leishmania spp., to humans. High toxicity, resistance and treatment failure of the available chemotherapy against visceral leishmaniosis demands the investigation of new anti-leishmanial compounds. Lupeol is a form of triterpene isolated from several medicinal plants and possesses an antimicrobial property. In this study, cytotoxic effect of lupeol was screened against the mammalian amastigotes form and insect promastigote form of Leishmania donovani, following three cycles of incubation at different concentrations by MTT assay. Resul

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Publication Date
Wed Sep 16 2020
Journal Name
Research Journal Of Pharmacy And Technology
Ex vivo study of anti-leishmanial activity of artemisinin against Leishmania tropica amastigote
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Leishmania parasites are the causative agent of leishmaniasis. Many studies are inspecting chemical drugs, including the use of miltefosine and amphotericin B, but curative values may be limited for these drugs with side effects due to the chemical origin, therefore, investigating less toxic therapies is essential. The aim of this study was to investigate the effectiveness of artemisinin on Iraqi strain of Leishmania tropica, by experimental macrophage ex vivo infection of amastigotes into mouse macrophage cell-line RAW264.7. Different concentrations (100, 200, 300, 400, 500)μM of artemisinin (ART) were screened to examine the susceptibility of L. tropica amastigotes to invade macrophage cell line along three times of follow up (24, 48 and

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Scopus
Publication Date
Thu Dec 31 2020
Journal Name
College Of Islamic Sciences
The cultural identity in the novel "The American Granddaughter" by writer InamKaghi
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The identity of the cultural identity of the party (the ego and the other) during a series of questions subject to the transformations of history and the process of culture, the search of identity and its characteristics within the novel discourse calls to address the cultural impact communication discourse aims to reveal the functional and intellectual benefits that contributed to the formation of cultural identity, and stand at the most important manifestations And the secretions that mimic a world remains part of it present in the imagination of the producer of the text is moving in accordance with the holistic perception of the world embedded between the lines of the trial.The question of identity as an intellectual dimension in orde

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Publication Date
Sun Mar 04 2012
Journal Name
Baghdad Science Journal
The genetic inhibition of some pathogenic bacterial isolates related to Enterobacteriaceae by using Different leaves extracts of Cider (Nabag) Zizyphus spina-christa
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The plant Zizyphus spina-christa grows wildly in the middle and southern of Iraq locally named Nabag. In this study the antibacterial activity of several different plant extract (alcoholic hot and cold extract 80%, aqueous hot and cold extract) was tested against some gram negative bacteria that related to Enterobacteriacea as follow; Pseudomonas aeruginosa, Escherchia coli Proteus mirabilis, Serratia mercesence,. Aeromonas sp, Klebsiella pneumoniae ,Shigella sp, Salmonella enteritidis (134), S. typhi(97), S. typhimurium (300) , S. typhi, . The results showed that efficient method of extract was alcoholic hot extract from other extract methods that are used in this study. The detection of active compound in crude extracts of the leaves show

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