Impact of an indigenously produced multi-enzyme complex from Bacillus subtilis KT004404 on growth and blood parameters in broiler chicken.

A 42-days experiment was conducted on a day old birds (n = 400) to evaluate the effect of enzyme supplements in feed on the growth, blood parameters, phosphorous content in bones, and nitrogen retention. Different treatments included: control (C) without enzyme supplement, while the other three groups included enzyme mixture T1 and T2 with two commercially available enzyme mix, and T3 with indigenously produced multi-enzyme complex from Bacillus subtilis KT004404. Birds that were fed with indigenously produced multi-enzyme complex showed significant weight gain as compared to other groups.

Novel coumarin-isatin hybrids as potent antileishmanial agents: Synthesis, in silico and in vitro evaluations.

Leishmaniasis being one of the six major tropical diseases that affects nearly 0.7-1.3 million people annually, has so far limited and high toxic therapeutic options.

Isolation and Characterization of Leishmanial Adenine Aminohydrolase as a Drug Target.

Background: Search for new drug targets is becoming imperative these days, given that marketed chemotherapeutic drugs have lost their efficacy against harmful agents because of adaptability to climatic changes and co-evolving vectors to new hosts. In the wake of such a challenge, the prominence of biochemical studies is increasing by way of exploring selective enzymes and investigating their structural and functional properties through biochemical kinetic parameter Km for the application of IC50 using designed drugs. Recently, discovered Adenine Aminohydrolase (EC 3.

Synthesis and computational studies of highly selective inhibitors of human recombinant tissue non-specific alkaline phosphatase (h-TNAP): A therapeutic target against vascular calcification.

In this study, we have discovered small druglike molecules as selective inhibitors of human tissue-nonspecific alkaline phosphatase (h-TNAP), an enzyme critical for the regulation of extracellular matrix calcification. The upregulation of h-TNAP is associated with various pathologies particularly the vascular calcification (VC). Selective inhibition of h-TNAP over h-NPP1 may serve as a useful therapeutic strategy against vascular calcification.

Reactive oxygen species generating photosynthesized ferromagnetic iron oxide nanorods as promising antileishmanial agent.

To investigate the photodynamic therapeutic potential of ferromagnetic iron oxide nanorods (FIONs), using as a reducing agent, against . FIONs were characterized using ultraviolet visible spectroscopy, x-ray diffraction and scanning electron microscopy. FIONs showed excellent activity against promastigotes and amastigotes (IC 0.

Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation.

Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility-with extensive first-pass metabolism-can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability.

Mannosylated thiolated paromomycin-loaded PLGA nanoparticles for the oral therapy of visceral leishmaniasis.

Aim: The present study evaluates the efficacy of paromomycin (PM)-loaded mannosylated thiomeric nanoparticles for the targeted delivery to pathological organs for the oral therapy of visceral leishmaniasis.

Materials & Methods: Mannosylated thiolated chitosan (MTC)-coated PM-loaded PLGA nanoparticles (MTC-PLGA-PM) were synthesized and evaluated for morphology, drug release, permeation enhancing and antileishmanial potential.

Results: MTC-PLGA-PM were spherical in shape with a size of 391.

Design of mannosylated oral amphotericin B nanoformulation: efficacy and safety in visceral leishmaniasis.

The aim of this study was to evaluate mannose-anchored thiolated chitosan (MTC) based nanocarriers (NCs) for enhanced permeability, improved oral bioavailability and anti-parasitic potential of amphotericin B (AmB). Transgenic Leishmania donovani parasites expressing red fluorescent protein DsRed2 and imaging-flow cytometry was used to investigate parasitic burdens inside bone marrow-derived macrophages ex vivo. Cytokine estimation revealed that MTC nanocarriers activated the macrophages to impart an explicit immune response by higher production of TNF-α and IL-12 as compared to control.

Mannosylated thiolated polyethylenimine nanoparticles for the enhanced efficacy of antimonial drug against Leishmaniasis.

Aim: Our aim was to inhibit trypanothione reductase (TR) and P-gp efflux pump of Leishmania by the use of thiolated polymers. Thus, increasing the intracellular accumulation and therapeutic effectiveness of antimonial compounds.

Methods: Mannosylated thiolated chitosan and mannosylated thiolated chitosan-polyethyleneimine graft were synthesized and characterized.

Redox biology of Leishmania and macrophage targeted nanoparticles for therapy.

Intramacrophage parasite 'Leishmania' has developed various mechanisms for proficient uptake into macrophages and phagosome regulation to avoid macrophage's oxidative burst induced by peroxide, hydroxyl radical, hypochlorous acid and peroxynitrite production. One major barrier for impairing the accession of old fashioned anti-Leishmanial drugs is intrinsic incapability to pass through cell membranes and limiting their abilities to ultimately destroy intracellular pathogens. Receptor-mediated targeted drug delivery to the macrophages by using nanoparticles emerges as promising strategy to improve therapeutic efficacy of old-fashioned drug.

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis.

Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized.

Materials & Methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized.

Annihilation of Leishmania by daylight responsive ZnO nanoparticles: a temporal relationship of reactive oxygen species-induced lipid and protein oxidation.

Lipid and protein oxidation are well-known manifestations of free radical activity and oxidative stress. The current study investigated extermination of Leishmania tropica promastigotes induced by lipid and protein oxidation with reactive oxygen species produced by PEGylated metal-based nanoparticles. The synthesized photodynamic therapy-based doped and nondoped zinc oxide nanoparticles were activated in daylight that produced reactive oxygen species in the immediate environment.

Photo-induced Leishmania DNA degradation by silver-doped zinc oxide nanoparticle: an in-vitro approach.

Recently, the authors reported newly synthesised polyethylene glycol (PEG)ylated silver (9%)-doped zinc oxide nanoparticle (doped semiconductor nanoparticle (DSN)) which has high potency for killing Leishmania tropica by producing reactive oxygen species on exposure to sunlight. The current report is focused on Leishmania DNA interaction and damage caused by the DSN. Here, we showed that the damage to Leishmania DNA was indirect, as the DSN was unable to interact with the DNA in intact Leishmania cell, indicating the incapability of PEGylated DSN to cross the nucleus barrier.

Structure based medicinal chemistry-driven strategy to design substituted dihydropyrimidines as potential antileishmanial agents.

In an attempt to explore novel and more potent antileishmanial compounds to diversify the current inhibitors, we pursued a medicinal chemistry-driven strategy to synthesize novel scaffolds with common pharmacophoric features of dihydropyrimidine and chalcone as current investigational antileishmanial compounds. Based on the reported X-ray structure of Pteridine reductase 1 (PTR1) from Leishmania major, we have designed a number of dihydropyrimidine-based derivatives to make specific interactions in PTR1 active site. Our lead compound 8i has shown potent in vitro antileishmanial activity against promastigotes of L.

Antileishmanial, DNA Interaction, and Docking Studies of Some Ferrocene-Based Heteroleptic Pentavalent Antimonials.

A series of ferrocenyl pentavalent antimonials (1-8) were synthesized and characterized by elemental analysis, FT-IR, and multinuclear ((1) H and (13) C) NMR spectroscopy. These antimonials were evaluated for their antileishmanial potential against Leishmania tropica KWH23, and by biocompatibility and membrane permeability assays. Moreover, mechanistic studies were carried out, mediated by DNA targeting followed by computational docking of ferrocenyl antimonials against the leishmanial trypanothione reductase enzyme.

Visible-light-responsive ZnCuO nanoparticles: benign photodynamic killers of infectious protozoans.

Human beings suffer from several infectious agents such as viruses, bacteria, and protozoans. Recently, there has been a great interest in developing biocompatible nanostructures to deal with infectious agents. This study investigated benign ZnCuO nanostructures that were visible-light-responsive due to the resident copper in the lattice.

PEGylated silver doped zinc oxide nanoparticles as novel photosensitizers for photodynamic therapy against Leishmania.

We describe daylight responsive silver (Ag) doped semiconductor nanoparticles of zinc oxide (DSNs) for photodynamic therapy (PDT) against Leishmania. The developed materials were characterized by X-ray diffraction analysis (XRD), Rutherford backscattering (RBS), diffused reflectance spectroscopy (DRS), and band-gap analysis. The Ag doped semiconductor nanoparticles of zinc oxide were PEGylated to enhance their biocompatibility.

Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy.

UGT1A1 gene mutations in Pakistani children suffering from inherited nonhemolytic unconjugated hyperbilirubinemias.

Two inherited unconjugated hyperbilirubinemias, Crigler-Najjar syndrome and Gilbert syndrome, arise due to deficiency of UGT1A1 enzyme activity. Crigler-Najjar syndrome type 1 (CN1) lies at the extreme severe end of the spectrum of UGT1A1 activity characterized by complete absence, followed by the less severe Crigler-Najjar syndrome type 2 (CN2). Gilbert syndrome is the mild form having only partial loss of UGT1A1 activity.

Antimicrobial, crown gall tumor inhibitory and cytotoxicity assays of N-[(1-methyl-1H-indole-3-yl)methylene]amines synthesized by an improved protocol.

The present paper reports an easy preparation of imines of N-methyl-1H-indole-3-carboxaldehyde by its condensation with alkyl and aromatic amines in ethanol without using any catalyst or dehydrating agent. The compounds have been screened for their antibacterial, antifungal, crown gall tumor inhibitory, and cytotoxic activities. As a major finding some of the compounds exhibited potential biological activity.

Evaluation of some classical hydrazones of ketones and 1,2-diketones as antileishmanial, antibacterial and antifungal agents.

The paper describes the synthesis and antimicrobial (antileishmanial, antibacterial and antifungal) activity of some classical hydrazones of benzophenones and of 1,2-diketones. N-(Diaryl) acyl derivatives of these hydrazones have also been synthesized and evaluated. 4,4,-Demthoxybenzil monohydrazone and 4,4'-dimethoxybenzophenone hydrazone showed significant antileishmanial activity.

Synthesis of N-(1-methyl-1H-indol-3-yl)methyleneamines and 3,3-diaryl-4-(1-methyl-1H-indol-3-yl)azetidin-2-ones as potential antileishmanial agents.

A series of N-(1-methyl-1H-indol-3-yl)methyleneamines and eight new 3,3-diaryl-4-(1-methyl-1H-indol-3-yl)azetidin-2-ones have been synthesized and screened for their antileishmanial activity against Leishmania major. 3,3-Diaryl-4-(1-methyl-1H-indol-3-yl)azetidin-2-ones have been synthesized by the Staudinger's ketene-imine cycloaddition employing two 2-diazo-1,2-diarylethanones as the precursors of diarylketenes. A marked improvement in anti-parasitic activity is observed by transformation of the methyleneamines to azetidin-2-ones in seven out of eight compounds.

A novel missense mutation in the ectodysplasin-A (EDA) gene underlies X-linked recessive nonsyndromic hypodontia.

Background: Nonsyndromic hypodontia or congential absence of one or more permanent teeth is a common anomaly of dental development in humans. This condition may be inherited in an autosomal (dominant/recessive) or X-linked (dominant/recessive) mode. Mutations in three genes, PAX9, MSX1, and AXIN2, have been determined to be associated with autosomal dominant and recessive tooth agenesis.

Effect of different wavelengths on superoxide dismutase.

Introduction: Superoxide dismutase (SOD) is one of the most important antioxidant enzymes present in all oxygen-metabolizing cells. This enzyme eliminates toxins from our body, so it is vital to understand its action and activity under the influence of different wavelengths. The effects of different wavelengths of light in the visible range on SOD activity were investigated.