1,720,986 research outputs found
Redox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania
No full textLeishmaniasis, a vector-borne disease, is caused by intracellular parasite Leishmania donovani. Unlike most intracellular pathogens, Leishmania donovani are lodged in parasitophorous vacuoles and replicate within the phagolysosomes in macrophages. Effective vaccines against this disease are still under development, while the efficacy of the available drugs is being questioned owing to the toxicity for nonspecific distribution in human physiology and the reported drug-resistance developed by Leishmania donovani. Thus, a stimuli-responsive nanocarrier that allows specific localization and release of the drug in the lysosome has been highly sought after for addressing two crucial issues, lower drug toxicity and a higher drug efficacy. We report here a unique lysosome targeting polymeric nanocapsules, formed via inverse mini-emulsion technique, for stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line. A benign polymeric backbone, with a disulfide bonding susceptible to an oxidative cleavage, is utilized for the organelle-specific release of miltefosine. Oxidative rupture of the disulfide bond is induced by intracellular glutathione (GSH) as an endogenous stimulus. Such a stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line over a few hours helped in achieving an improved drug efficacy by 200 times as compared to pure miltefosine. Such a drug formulation could contribute to a new line of treatment for leishmaniasis.A. Das acknowledges SERB (India) Grants (CRG/2020/000492 and JCB/2017/000004) and DBT Grant (BT/PR22251/NNT/28/1274/2017) for supporting this research. N. Mukherjee acknowledges SERB (India) Grant PDF/2016/001437 and K. Das acknowledges the grant EMR/2015/001674 for supporting this research. Financial support from DST (DST/INSPIRE/03/2017/002477) is acknowledged by R.T. This manuscript bears CSMCRI registration no 7/2021.Pramanik, SK (corresponding author), CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India.
Mukherjee, N (corresponding author), CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, Kolkata 700032, India.
Chattopadhy, S (corresponding author), BITS Pilani, Pilani 403726, Goa, India.
Das, A (corresponding author), Indian Inst Sci Educ & Res Kolkata, Mohanpur 741246, W Bengal, India.
[email protected]; [email protected]; [email protected]
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]
Dual-Enzyme Encapsulated Porous Nanocapsules for Lysosome-Targeted, Hypoxia-Amplified Cancer Therapy
No full textGlucose oxidase (GOx) catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide (H2O2), while horseradish peroxidase (HRP) converts H2O2 into cytotoxic hydroxyl radicals (center dot OH) under acidic conditions, such as those in lysosomes. Harnessing this tandem enzymatic activity offers a promising strategy to exacerbate tumor hypoxia and induce cancer cell death. Herein, we report the synthesis of hollow, porous organic nanocapsules (HPOCs; average diameter similar to 145 nm, wall thickness similar to 11 nm) via an inverse mini-emulsion technique using functionalized diamine and tetracarbaldehyde precursors. These nanocapsules coencapsulate GOx and HRP while acting as size-exclusion membranes, allowing selective diffusion of small molecules while retaining the enzymes. Confocal studies with BODIPY-labeled GOx and Cy5-labeled HRP ensure the encapsulation of both enzymes within the HPOCs and are found to be localized in the lysosome. The HPOCs exhibit excellent biocompatibility and, under hypoxic conditions, trigger substantial cancer cell apoptosis (similar to 75% cell death) and G2/M cell cycle arrest. Control nanocapsules lacking either or both enzymes show negligible therapeutic effect, underscoring the synergistic mechanism. This work presents a proof-of-concept for two-enzyme-loaded HPOCs as an effective platform for synergistic, hypoxia-amplified cancer therapy.A.D. acknowledges SERB (India) for financial support through JBR/2023/000005 grants. A.D. also acknowledges the MoESTARS research grant (STARS2/2023-47). S.K.P. acknowledges a mobility grant funded by the BOF Special Research Fund of Hasselt University. We acknowledge Biorender for the use of their software to generate the graphics. CSIR-CSMCRI PRIS no 133/2025
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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