Leishmania donovani Modulates Macrophage Lipidome During Infection.

Obligate intracellular protozoan parasite, Leishmania donovani, causative agent of visceral leishmaniasis, led to impaired macrophage functions. It is well documented that many of these changes were induced by parasite-mediated reduction in macrophage cholesterol content. Leishmania-mediated alteration in the other lipids has not been explored in detail yet.

Leishmania donovani modulates host miRNAs regulating cholesterol biosynthesis for its survival.

Cholesterol reduction by intracellular protozoan parasite Leishmania donovani (L. donovani), causative agent of leishmaniasis, impairs antigen presentation, pro-inflammatory cytokine secretion and host-protective membrane-receptor signaling in macrophages. Here, we studied the miRNA mediated regulation of cholesterol biosynthetic genes to understand the possible mechanism of L.

Evaluating complete surface-associated and secretory proteome of Leishmania donovani for discovering novel vaccines and diagnostic targets.

The protozoa Leishmania donovani causes visceral leishmaniasis (kala-azar), the third most common vector-borne disease. The visceral organs, particularly the spleen, liver, and bone marrow, are affected by the disease. The lack of effective treatment regimens makes curing and eradicating the disease difficult.

Exploration of potential inhibitors for autophagy-related protein 8 as antileishmanial agents.

Leishmaniasis is considered a tropical neglected disease, which is caused by an intramacrophagic parasite, Leishmania. It is endemic in 89 different countries. Autophagy-related protein 8 (Ldatg8) is responsible for the transformation of parasites from promastigote to amastigote differentiation.

Sesamol Induces Apoptosis-Like Cell Death in .

Background: Visceral leishmaniasis (VL), caused by the protozoan parasite (), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance.

Embilica officinalis L. inhibits the growth and proliferation of Leishmania donovani through the induction of ultrastructural changes, mitochondrial dysfunction, oxidative stress and apoptosis-like cell death.

Visceral leishmaniasis (VL) is caused by a protozoan parasite, Leishmania donovani (L. donovani). It affects around 1-2 million people around the world annually.

Virtual screening of natural compounds for potential inhibitors of Sterol C-24 methyltransferase of Leishmania donovani to overcome leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania. Leishmaniasis is transmitted from one human to other through the bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region.

Repurposing of FDA-approved drugs as inhibitors of sterol C-24 methyltransferase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L.

Targeting sterol alpha-14 demethylase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha-14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation.

Antileishmanial Evaluation of Bark Methanolic Extract of : and Studies.

( is an important medicinal plant, found in Africa, the Middle East, and the Indian subcontinent. Every part of the plant possesses a wide array of biologically active and therapeutically important compounds. We reported the antileishmanial activity of bark methanolic extract through antileishmanial assays and dissected the mechanism of its action through studies.

Hesperidin Targets Sterol C-24 Reductase to Fight against Leishmaniasis.

Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found effective against an array of pathogens including fungi, bacteria, viruses, and protozoa. Here, we evaluated its antileishmanial activity and possible mechanism of action through different and experiments.

Assessment of the Antileishmanial Potential of Leaf Extract.

has a wide array of biologically active and therapeutically important class of compounds. important drug targets, sterol 24-c methyltransferase (SMT), trypanothione reductase (TR), pteridine reductase (PTR1), and nucleoside hydrolase (NH), were modelled, and molecular docking was performed against the abundant phytochemicals of its leaf extract. Molecular docking results provided the significant prima facie evidence of the leaf extract to have antileishmanial potential.

Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins.

Background And Aim: COVID-19 emerged by the end of 2019 in Wuhan, China. It spreaded and became a public health emergency all over the world by mid of April 2020. Flavonoids are specialized metabolites that have antimicrobial properties including anti-viral activity.

Cynaroside inhibits Leishmania donovani UDP-galactopyranose mutase and induces reactive oxygen species to exert antileishmanial response.

Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.

Development and Characterization of an Avirulent Strain.

causes cutaneous leishmaniasis. An antileishmanial vaccine for humans is unavailable. In this study, we report development of two attenuated strains-5ASKH-HP and LV39-HP-by continuous culture (high passage) of the corresponding virulent strains (low passage).

Experimental and Theoretical Studies of Novel Azo Benzene Functionalized Conjugated Polymers: In-vitro Antileishmanial Activity and Bioimaging.

To study the effect of insertion of azobenzene moiety on the spectral, morphological and fluorescence properties of conventional conducting polymers, the present work reports ultrasound-assisted polymerization of azobenzene with aniline, 1-naphthylamine, luminol and o-phenylenediamine. The chemical structure and polymerization was established via Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (H-NMR) spectroscopy, while the electronic properties were explored via ultraviolet-visible (UV-vis) spectroscopy. Theoretical IR and UV spectra were computed using DFT/B3LYP method with 6-311G basis set while theoretical H-NMR spectra was obtained by gauge independent atomic orbital (GIAO) method.

Repurposing Glyburide as Antileishmanial Agent to Fight Against Leishmaniasis.

Background: Leishmaniasis is caused by a protozoan parasite, Leishmania. It is common in more than 98 countries throughout the world. Due to insufficient availability of antileishmanial chemotherapeutics, it is an urgent need to search for new molecules which have better efficacy, low toxicity and are available at low cost.

Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischaemia and its toxicity assessment.

Objective: Enhancement of CS-GA-PCL-NPs (Glycyrrhizic Acid-encapsulated-chitosan-coated-PCL-Nanoparticles) bioavailability in brain.

Methods: Double emulsification solvent evaporation method in order to develop CS-PCL-NPs (Chitosan-coated-PCL-Nanoparticles) followed by characterization of particle size and distribution, zeta potential, encapsulation efficiency and drug release (in vitro). To determine drug-uptake and its pharmacokinetic profile in brain as well as plasma, UHPLC (triple quadrupole Q-trap) MS/MS method was developed and optimized for CS-GA-PCL-NPs as well as to follow-up examined effective role of optimized NPs in reduction of all brain injury parameters after MCAO through the grip strength, locomotor activity, inflammatory cytokines levels, measurement of infarction volume and histopathological changes in neurons with safety/toxicity after i.

In silico studies and evaluation of antiparasitic role of a novel pyruvate phosphate dikinase inhibitor in Leishmania donovani infected macrophages.

The present work deals with the identification and characterization of a novel inhibitor Z220582104, specific to pyruvate phosphate dikinase, for leishmanicidal activities against free promastigotes and intracellular amastigotes. We have used structure-based drug designing approaches and performed homology modelling, virtual screening and molecular dynamics studies. Primary mouse macrophages and macrophage cell line J774A1 were infected with promastigotes of Leishmania donovani.

Bacterial imbalance and gut pathologies: Association and contribution of E. coli in inflammatory bowel disease.

Hosts and microbes have co-evolved over millions of years. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated diseases. Although the etiology of IBD remains an enigma, various studies have proposed the involvement of mucosa-associated Escherichia coli (E.

Sphingosine-1-phosphate signaling in Leishmania donovani infection in macrophages.

Background: Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array of cellular processes, such as apoptosis, cell proliferation, migration, and differentiation, but its role in Leishmania donovani infection is unknown.

Methodology/ Principal Findings: In the present study, we observed that L. donovani infection in THP-1 derived macrophages (TDM) leads to decrease in the expression of S1pr2 and S1pr3 at mRNA level.

Leishmania donovani infection differentially regulates small G-proteins.

Leishmania is a protozoan parasite that resides and replicates in macrophages and causes leishmaniasis. The parasite alters the signaling cascade in host macrophages and evades the host machinery. Small G-proteins are GTPases, grouped in 5 different families that play a crucial role in the regulation of cell proliferation, cell survival, apoptosis, intracellular trafficking, and transport.

Identification of novel inhibitors against UDP-galactopyranose mutase to combat leishmaniasis.

Leishmania, a protozoan parasite that causes leishmaniasis, affects 1-2 million people every year worldwide. Leishmaniasis is a vector born disease and characterized by a diverse group of clinical syndromes. Current treatment is limited because of drug resistance, high cost, poor safety, and low efficacy.

Influence of Luminol Doping of Poly(o-phenylenediamine) on the Spectral, Morphological, and Fluorescent properties: A Potential Fluorescent Marker for Early detection and Diagnosis of Leishmania donovani.

There has been a steady progress in the development of doped conjugated polymers to remarkably improve their photo physical properties for their application as biomarkers. With a view to enhance the spectral, morphological, and photo physical properties of poly(o-phenylenediamine) (POPD), the present work reports the synthesis of poly(o-phenylenediamine) and doping of this polymer using luminol. The formation of luminol-doped POPD was confirmed by infrared and ultraviolet-visible spectroscopies and X-ray diffraction studies.

Implication of sphingosine-1-phosphate signaling in diseases: molecular mechanism and therapeutic strategies.

Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that is initiated by the intracellular production of bioactive lipid molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its extracellular receptors activates diverse downstream signaling that play a critical role in governing physiological processes. Increasing evidence suggests that this signaling pathway often gets impaired during pathophysiological and diseased conditions and hence manipulation of this signaling pathway may be beneficial in providing treatment.