61 research outputs found
Mosquitocidal, Antimalarial and Antidiabetic Potential of Musa paradisiaca-Synthesized Silver Nanoparticles: In Vivo and In Vitro Approaches
No full textThe development of pathogens and parasites resistant to synthetic drugs has created the need for developing alternative approaches to fight vector-borne diseases. In this research, we fabricated green-synthesized silver nanoparticles (AgNP) using Musa paradisiaca stem extract as a reducing and stabilizing agent. AgNP showed plasmon resonance reduction under UV–Vis spectrophotometry, SEM and XRD highlighted that they were crystalline in nature with face centered cubic geometry. The FTIR spectrum of AgNP exhibited main peaks at 464.74, 675.61, 797.07, 1059.42, 1402.58, 1639.69, 2115.61 and 3445.75 cm−1. AgNP showed growth inhibition activity against bacteria and fungi of public health relevance. AgNP were a valuable candidate for treatment of diabetes in STZ-treated rat by normalizing glucose, galactose and insulin. AgNP were toxic against larvae and pupae of the malaria vector Anopheles stephensi, with LC50 of 3.642 (I), 5.497 (II), 8.561 (III), 13.477 (IV), and 17.898 ppm (pupae), respectively. Furthermore, the antiplasmodial activity of nanoparticles was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum, IC50 were 84.22 μg/ml (CQ-s) and 89.24 μg/ml (CQ-r), while chloroquine IC50 were 86 μg/ml (CQ-s) and 91 μg/ml (CQ-r). Overall, we add knowledge on the multipurpose effectiveness of green-fabricated nanoparticles in medicine and parasitology, which can be potentially helpful to develop newer and safer antiplasmodial agents and vector control tools
Die Rolle von Rho-GTPasen bei der Migration von Stamm- und Progenitorzellen
No full textStem cells capable of self-renewal and differentiation into multiple tissues are important in medicine to reconstitute the hematopoietic system after myelo-ablative chemo- or radiotherapy. In the present situation, adult stem cells such as Mesenchymal stem cells (MSC) and Hematopoietic stem cells (HSC) are used for therapeutic purposes. For tissue regeneration and tissue constitution, engraftment of transplanted stem cells is a necessary feature. However, in many instances, the transplanted stem cells reach the tissues with low efficiency. Considering the three-step model of leukocyte extravasation by Springer et al, the rolling, adhesion and transmigration form the three major steps for the transplanted stem cells to enter the desired tissues. One of the molecular switches reported to be involved in these mechanisms are the Rho family GTPases. The present study investigates the role of Rho GTPases in adhesion and migration of stem and progenitor cells. Chemotactic and chemokinetic migration assays, transendothelial migration assays, migration of cells under shear stress, microinjection, retroviral and lentiviral gene transfer methods, oligonucleotide microarray analysis and pull down assays were employed in this study for the elucidation of Rho GTPase involvement in migration and adhesion of stem and progenitor cells. The transmigration assay used for the migration determination of the adherent cell type, MSC, was optimized for the efficient and effective assessment of the migrating cells. The involvement of Rho was found to be critical for stem and progenitor cell migration where inactivation of Rho by C2I-C3 transferase toxin and/or overexpression of C3 transferase cDNA increased the migration rate of Hematopoietic progenitor cells (HPC) and MSC. Moreover, modulation of Rho caused predictable cytoskeletal and morphological changes in MSC. Assessment of Rho GTPase involvement in the interacting partner, the endothelial cells during stem cell migration, revealed that active Rho expression induced E-selectin expression. The increased levels of E-selectin were functionally confirmed by the increased adhesion of progenitor cells (HPC) to the Human umbilical vein endothelial cell (HUVEC) layer. Moreover, inhibition of Rac in the migrating endothelial progenitor cells (eEPC) increased their adhesion to HUVEC correlating with the increased percentage expression of cell surface receptor, CD44 in Rac inactivated eEPC. In conclusion, this study shows that Rho GTPases control the adhesion and migration of stem and progenitor cells, HPC and MSC. Rho inhibition drives the cells to migrate in the blood vessels. The substantial increase in the level of active Rho in endothelial layer, manifested by the E-selectin surface expression assists the better adhesion of stem and progenitor cells to the endothelial layer. Serum factors and growth factors in the physiological system influence the Rho GTPase expression in both migrating stem cells and the barrier endothelial cells. Thus, specific modulation of Rho GTPases in the transplanted stem and progenitor cells could be an interesting tool to improve the migration and homing processes of stem cells for cellular therapy in future.Stammzellen zeichnen sich durch die Fähigkeit zu Selbst-Erneuerung und Differenzierbarkeit in unterschiedliche Gewebe aus. Dies macht sie zur Anwendung in der Medizin attraktiv. Gegenwärtig werden adulte Stammzellen wie mesenchymale Stammzellen (MSC) und hämatopoietische Stammzellen (HSC) zu therapeutischen Zwecken transplantiert. Mesenchymale Stammzellen werden seit einigen Jahren als interessantes Mittel zur Organregeneration z.B. des Herzens diskutiert, während hämatopoietische Stammzellen medizinisch zur Rekonstitution des hämatopoietischen Systems nach myeloablativer Therapie eingesetzt werden. Notwendig ist hierbei das Anwachsen der transplantierten Stammzellen im Empfänger; in vielen Fällen aber geschieht dies nur mit sehr geringer Effizienz. In diesem Zusammenhang interessant ist die Anwendung des dreischrittigen Modells von Springer et al. für die Auswanderung von Leukozyten aus den Blutgefäßen ins Gewebe auf Stammzellen, das Rolling, Adhäsion und Transmigration von Zellen als die entscheidenden Schritte beschreibt. Nach der Transplantation, die in der Regel in den Blutkreislauf erfolgt, wandern Stammzellen selbständig in die Blut bildenden Organe ein, die ihr eigentliches "Zuhause" im Körper sind. Ein wichtiger molekularer Schalter bei diesen "homing"-Mechanismen sind die so genannten Rho-GTPasen (ras-homologe Guanosin-Triphosphatasen). Die vorliegende Arbeit untersucht die Bedeutung der Rho-GTPasen für die Adhäsion und Migration von Stamm- und Vorläuferzellen. Durch die Analyse der chemotaktischen und chemokinetischen Migration, transendothelialer Migration, Migration von Zellen unter Scher-Stress, Mikroinjektion, retrovirale und lentivirale Gentransfermethoden, Oligonukleotid-Mikroarrays und Pull-Down-Assay wurde versucht, die Rolle von Rho-GTPasen bei der Migration und Adhaesion von Stamm- und Vorlaeuferzellen aufzuklaeren. Die Versuchsbedingungen für Migrationsexperimente mit MSC - adhärenten Stammzellen - wurden zunächst optimiert, um das Wanderungsverhalten der Zellen effektiv erfassen und darstellen zu können. Die Bedeutung von Rho für die Migration von Stamm- und Vorläuferzellen zeigte sich, als die Inaktivierung von Rho durch C2I-C3-Transferase-Toxin und/oder Ueberexpression von C3-Transferase-cDNA in den Migrationsexperimenten überraschenderweise die chemokinetische Migration von HPC und MSC signifikant erhöhte. Außerdem bewirkte eine Modulation von Rho durch Expression dominant-negativer bzw. konstitutiv-aktiver Varianten deutliche Veränderungen in der Morphologie und im Zytoskelett von MSC. Die Analyse der Rho-GTPasen in Endothel-Zellen als den interagierenden Partnern der Stammzellen während ihrer Migration aus den Blutgefäßen in die Gewebe zeigte, dass eine erhöhte Rho-Expression mit einer erhöhten E-Selektin-Expression korrelierte. Die erhöhte E-Selektin-Expression im Endothel konnte funktionell bestätigt werden durch eine erhöhte Adhäsion von Vorläuferzellen an das Endothel. Nicht zuletzt erhöhte die Inhibition von Rac in migrierenden endothelialen Vorläuferzellen (eEPC) deren Adhäsion an HUVEC, korrelierend mit der erhöhten Expression des E-Selektin-Liganden CD44 in diesen Zellen. Zusammengefasst zeigt diese Arbeit, dass Rho-GTPasen die Adhäsion und Migration von Stamm- und Vorläuferzellen regulieren. Inhibiton von Rho führt zu erhöhter Mobilisation dieser Zellen in den Blutkreislauf. Die Zunahme der aktiven Form von Rho in den Zellen des Endothels, die sich in erhöhter E-Selektin-Expression auf den Zellen manifestiert, führt zu einer Erhöhung der Adhäsion von Stamm- und Vorläuferzellen an das Endothel. Wachstumsfaktoren und Faktoren im Serum beeinflussen die Expression von Rho-GTPasen sowohl in zirkulierenden Stammzellen als auch im Endothel. Deshalb könnte eine spezifische Regulation der Rho-GTPasen in transplantierten Stamm- und Vorläuferzellen ein wichtiges Mittel zur Verbesserung der Transplantationseffizienz und damit der Stammzelltherapie insgesamt sein
Nanocapsules with stimuli-responsive moieties for controlled release employing light and enzymatic triggers
No full textThe development of stimuli-responsive nanomaterials, that possess tailored functional properties for the release of specific compounds, is of particular interest. To this extent, controlling the release of molecules at the desired target is an important parameter to regulate chemical and/or biological reactions at a more profound level in a wide variety of applications. In the present work, we report on the development of dual-responsive thiourethane-urethane nanocapsules synthesizedviaan interfacial polymerization reaction executed at the droplet interface using the inverse miniemulsion technique. Evidenceviamorphological and controlled release investigations indicate that our nanocapsules are able to encapsulate hydrophilic compounds with high efficiency in their aqueous core and allow for its selective release upon exposure to UV light and the enzyme esterase. Moreover, we demonstrate the efficient encapsulation of the fragrance molecule geranyl acetate and the anticancer drug doxorubicin. For the latter, we demonstrate its apoptotic effect after being released in MCF 7 breast cancer cells. Overall, these nanocapsules can be used for a wide variety of applications where a selective release of the payload is desired.S. S. is an SB PhD Fellow at the FWO (Research Foundation Flanders). S. K. P. acknowledges BOF funding from Hasselt University. This work is supported by Hasselt University and the Research Foundation Flanders (FWO Vlaanderen; Hercules project AUHL/15/2 - GOH3816N). The authors are thankful to Prof. M. Van Bael for access to the DLS device.Pramanik, SK; Ethirajan, A (corresponding author), Hasselt Univ, Inst Mat Res IMO, Wetenschapspk 1 & Agoralaan D, B-3590 Diepenbeek, Belgium; IMEC, Associated Lab IMOMEC, Wetenschapspk 1, B-3590 Diepenbeek, Belgium;
CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India.
[email protected]; [email protected]
Nanofabrication of Graphene Quantum Dots with High Toxicity Against Malaria Mosquitoes, Plasmodium falciparum and MCF-7 Cancer Cells: Impact on Predation of Non-target Tadpoles, Odonate Nymphs and Mosquito Fishes
No full textRecently, it has been highlighted an overlooked connection between the biting activity of Anopheles mosquitoes and the spread of cancer. The excellent physico-chemical properties of graphene quantum dots (GQDs) make them a suitable candidate for biomedical applications. We focused on the toxicity of GQDs against Plasmodium falciparum and its vector Anopheles stephensi, and their impact on predation of non-target mosquito predators. Biophysical methods, including UV–vis, photoluminescence, FTIR and Raman spectroscopy, XRD analysis and TEM, confirmed the effective GQD nanosynthesis. LC50 against A. stephensi ranged from 0.157 (larva I) to 6.323 ppm (pupa). The antiplasmodial activity of GQDs was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of P. falciparum. IC50 were 82.43 (CQ-s) and 85.17 μg/ml (CQ-r). In vivo experiments conducted on Plasmodium berghei infecting albino mice showed moderate activity of GQDs if compared to chloroquine. Concerning non-target effects, the predation efficiency of Gambusia affinis, Anax immaculifrons and Hoplobatrachus tigerinus post-treatment with GQDs was enhanced. Lastly, GQDs were toxic against MCF-7 breast cancer cell lines with an IC50 = 24.81 μg/ml, triggering apoptosis in treated cells. Overall, we highlighted the multipurpose potential of GQDs for the development of newer drugs in the fight against Anopheles vectors, Plasmodium parasites and breast cancer cells
PEGylating poly(p-phenylene vinylene)-based bioimaging nanoprobes
No full textHypothesis: Conjugated polymer nanoparticles (CNPs) have attracted considerable attention within bioimaging due to their excellent optical properties and biocompatibility. However, unspecific adsorption of proteins hampers their effective use as advanced bioimaging probes. Controlled methodologies made possible tailor-made functional poly(p-phenylene vinylene), enabling one-pot synthesis of CNPs containing functional surface groups. Hence, it should be feasible to PEGylate these CNPs to tune the uptake by cell lines representative for the brain without imparting their optical properties. Experiments: CNPs consisting of the statistical copolymer 2-(50-methoxycarbonylpentyloxy)-5-methoxy-1,4-phenylenevinylene and poly(2-methoxy-5-(30,70-dimethoxyoctyloxy)-1,4-phenylenevinylene) were fabricated by miniemulsion solvent evaporation technique. Surface carboxylic acid groups were used to covalently attach amine-terminated polyethylene glycol (PEG) of different molecular weights. We investigated the effect of grafting CNPs with PEG chains on their intrinsic optical properties, protein adsorption behavior and uptake by representative brain cell lines. Findings: PEGylation did not affect the optical properties and biocompatibility of our CNPs. Moreover, a significant decrease in protein corona formation and unspecific uptake in central nervous system cell lines, depending on PEG chain length, was observed. This is the first report indicating that PEGylation does not affect the CNPs role as excellent bioimaging tools and can be adapted to tune biological interactions with brain cells. (C) 2020 Elsevier Inc. All rights reserved.Support for confocal microscopy was given by Prof. dr. Marcel Ameloot and Dr. Hannelore Bove. Cells were kindly provided by Prof. dr. Annelies Bronckaers, Dr. Jo Mailleux and dra. Jasmine Vanmol. Technical support was given by Huguette Penxten, Christel Bocken and Erik Royackers. Dr. Neomy Zaquen is acknowledged for the synthesis of the conjugated polymers. MP is grateful for funding from the IWT (Agentschap voor Innovatie door Wetenschap en Technologie). SS is an SB PhD Fellow at the Research Foundation Flanders (FWO). The work was funded by the Belgian Charcot Foundation. TJ is grateful for funding from the FWO in the form of an Odysseus grant. This work was supported by Hasselt University and the Research Foundation Flanders (FWO Vlaanderen; Hercules project AUHL/15/2 -GOH3816N). Additional support from BELSPO in the form of the interuniversity attraction pole (IAP) program P7/05: Functional Supramolecular Systems is kindly acknowledged. We further acknowledge the Hercules Foundation for the project (LC-MS@UHasselt: Linear Trap QuadrupoleOrbitrap mass spectrometer.Ethirajan, A (corresponding author), Hasselt Univ, Inst Mat Res, Wetenschapspk 1, B-3590 Diepenbeek, Belgium.
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Earthworm-mediated synthesis of silver nanoparticles. A potent tool against hepatocellular carcinoma, Plasmodium falciparum parasites and malaria mosquitoes
No full textThe development of parasites and pathogens resistant to synthetic drugs highlighted the needing of novel, eco-friendly and effective control approaches. Recently, metal nanoparticles have been proposed as highly effective tools towards cancer cells and Plasmodium parasites. In this study, we synthesized silver nanoparticles (EW-AgNP) using Eudrilus eugeniae earthworms as reducing and stabilizing agents. EW-AgNP showed plasmon resonance reduction in UV-vis spectrophotometry, the functional groups involved in the reduction were studied by FTIR spectroscopy, while particle size and shape was analyzed by FESEM. The effect of EW-AgNP on in vitro HepG2 cell proliferation was measured using MTT assays. Apoptosis assessed by flow cytometry showed diminished endurance of HepG2 cells and cytotoxicity in a dose-dependent manner. EW-AgNP were toxic to Anopheles stephensi larvae and pupae, LC50 were 4.8 ppm (I), 5.8 ppm (II), 6.9 ppm (III), 8.5 ppm (IV), and 15.5 ppm (pupae). The antiplasmodial activity of EW-AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. EW-AgNP IC50 were 49.3 μg/ml (CQ-s) and 55.5 μg/ml (CQ-r), while chloroquine IC50 were 81.5 μg/ml (CQ-s) and 86.5 μg/ml (CQ-r). EW-AgNP showed a valuable antibiotic potential against important pathogenic bacteria and fungi. Concerning non-target effects of EW-AgNP against mosquito natural enemies, the predation efficiency of the mosquitofish Gambusia affinis towards the II and II instar larvae of A. stephensi was 68.50% (II) and 47.00% (III), respectively. In EW-AgNP-contaminated environments, predation was boosted to 89.25% (II) and 70.75% (III), respectively. Overall, this research highlighted the EW-AgNP potential against hepatocellular carcinoma, Plasmodium parasites and mosquito vectors, with little detrimental effects on mosquito natural enemies
Power relations Vs Personal Relations in the Selected Translations of O.Chandu Menon’s Indulekha
No full textThe novel has three English translations. The first English version was by John Willoughby Francis Dumergue, a friend of O. Chandu Menon. The latest one was by Dr. Anitha Devassia. The novel had several novelties in terms of theme and technique though Chandu Menon was trying to ‘translate’ an alien genre to Malayalam literature. Anitha Devasia’s translation came more than hundred years after the publication of the original and Dumergue’s translation. This paper intends to analyze the two translations to identify the translator more representative of the author using Bourdieu’s concept of habitus. Bourdieu defines habitus as “a general, transposable disposition, which carries out a systematic, universal appreciation - beyond the limits of what has been directly learnt- of the necessity inherent in learning conditions
Fabrication of nano-mosquitocides using chitosan from crab shells: Impact on non-target organisms in the aquatic environment
No full textMosquitoes are arthropods of huge medical and veterinary relevance, since they vector pathogens and parasites of public health importance, including malaria, dengue and Zika virus. Currently, nanotechnology is considered a potential eco-friendly approach in mosquito control research. We proposed a novel method of biofabrication of silver nanoparticles (AgNP) using chitosan (Ch) from crab shells. Ch-AgNP nanocomposite was characterized by UV–vis spectroscopy, FTIR, SEM, EDX and XRD. Ch-AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi obtaining LC50 ranging from 3.18 ppm (I) to 6.54 ppm (pupae). The antibacterial properties of Ch-AgNP were proved against Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi, while no growth inhibition was reported in assays conducted on Proteus vulgaris. Concerning non-target effects, in standard laboratory considtions the predation efficiency of Danio rerio zebrafishes was 68.8% and 61.6% against I and II instar larvae of A. stephensi, respectively. In a Ch-AgNP-contaminated environment, fish predation was boosted to 89.5% and 77.3%, respectively. Quantitative analysis of antioxidant enzymes SOD, CAT and LPO from hepatopancreas of fresh water crabs Paratelphusa hydrodromous exposed for 16 days to a Ch-AgNP-contaminated aquatic environment were conducted. Notably, deleterious effects of Ch-AgNP contaminating aquatic enviroment on the non-target crab P. hydrodromous were observed, particularly when doses higher than 8–10 ppm are tested. Overall, this research highlights the potential of Ch-AGNP for the development of newer control tools against young instar populations of malaria mosquitoes, also highlighting some risks concerned the employ of nanoparticles in aquatic environments
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