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Abstract The interest in functionalized cellulose nanocrystals (CNCs) for multiple biomedical application has been increasing in recent years. CNCs are suitable to functionalization with an array of polymers, generating chemically related nanomaterials with different morphologies, surface charges that can affect bioreactivity, including immune response. In this study, we sought to understand the mechanistic differences regarding immunological responses evoked by functionalized CNCs and whether surface charges play a role in this effect. We investigated the effect of a cationic, CNCs-poly(APMA), and an anionic, CNCs-poly(NIPAAm) derivatives on the secretion of inflammatory cytokines, mitochondria-derived ROS and mitochondrial function and antioxidant response as well as on endoplasmic reticulum (ER) stress, in human and murine inflammatory cells. The cationic CNCs-poly(APMA) evoked a more robust immunological response in murine cell line, while the anionic CNCs-poly(NIPAAm) showed a significant NLRP3 inflammasome-dependent and independent immunological response in human monocytes. Moreover, CNCs-poly(NIPAAm) induced greater formation of acidic vesicular organelles, mitochondrial ROS in non-stimulated cells while CNCs-poly(APMA) mainly affected mitochondrial function by decreasing the intracellular ATP. The differences on the biological responses may be related to the surface charges of CNCs, and their likely interactions with intra and extracellular biomolecules. Graphical abstract Unlabelled Image Highlights • Both cationic and anionic functionalized cellulose nanocrystals evoked immune response in vitro. • The extension of the immune response and the mechanisms diverge. • The differences on the responses may be related to the surface charges of functionalized cellulose nanocrystals. [ABSTRACT FROM AUTHOR]

Recently we have demonstrated that needle-like cationic cellulose nanocrystals (CNC-AEMA2) evoke immunological responses through NLRP3 inflammasome/IL-1β inflammatory pathway. In this study we demonstrated that curcumin, a naturally occurring polyphenolic compound isolated from Curcuma longa (Zingiberaceae), was able to suppress, at least in part, this immunological response, as observed by diminished IL-1β secretion in CNC-AEMA2-stimulated macrophages primed with LPS. Curcumin is a well-known antioxidant and anti-inflammatory natural compound and in addition to acting as “scavenger” of reactive oxygen species (ROS), it can also upregulates antioxidant enzymes. However, the mechanisms by which this natural compound exerts its protective activity is still under investigation. We hypothesize that curcumin may also affect S-glutathionylation of key proteins involved in the NLRP3 inflammasome/IL-1β pathway, and therefore impact their protein-protein interactions. The goal of this study was to investigate the effects of curcumin on the S-glutathionylation of NLRP3 induced by CNC-AEMA2 in LPS-primed mouse macrophages (J774A.1), as well as interactions among proteins of the NLRP3 inflammasome complex. Our main finding indicates that the addition of curcumin concomitantly with LPS caused the greatest decrease in NLRP3 S-glutathionylation and a respective increase in caspase-1 S-glutathionylation, which appears to favor protein-protein interactions in the NLRP3 complex. Taking together, our results suggest that, at least in part, the anti-inflammatory activity of curcumin is associated with changes in S-glutathionylation of key NLRP3 inflammasome components, and perhaps resulting in sustained complex assembly and suppression of IL-1β secretion. [ABSTRACT FROM AUTHOR]

This article proposes a holistic localisation framework for underwater robotic swarms to dynamically fuse multiple position estimates of an autonomous underwater vehicle while using fuzzy decision support system. A number of underwater localisation methods have been proposed in the literature for wireless sensor networks. The proposed navigation framework harnesses the established localisation methods in order to provide navigation aids in the absence of acoustic exteroceptive sensors navigation aid (i.e., ultra-short base line) and it can be extended to accommodate newly developed localisation methods by expanding the fuzzy rule base. Simplicity, flexibility, and scalability are the main three advantages that are inherent in the proposed localisation framework when compared to other traditional and commonly adopted underwater localisation methods, such as the Extended Kalman Filter. A physics-based simulation platform that considers environment's hydrodynamics, industrial grade inertial measurement unit, and underwater acoustic communications characteristics is implemented in order to validate the proposed localisation framework on a swarm size of 150 autonomous underwater vehicles. The proposed fuzzy-based localisation algorithm improves the entire swarm mean localisation error and standard deviation by 16.53% and 35.17%, respectively, when compared to the Extended Kalman Filter based localisation with round-robin scheduling. [ABSTRACT FROM AUTHOR]

Cellulose nanocrystals (CNCs) are utilized for a wide variety of important applications from nanofillers to potential drug delivery. CNCs have a fiber-like structure that can be modified with different moieties to change the physicochemical characteristics and proper suit to biomedical applications. However, these modifications also can lead to undesirable effects, such as robust immune response. Previously we demonstrated that cationic CNCs evoke immunological responses through NLRP3 inflammasome/IL-1β inflammatory pathway, and this effect is associated, at least in part, with changes in mitochondrial ROS. In this work we expend our studies by analyzing biological responses of series of newly modified CNCs designed for different biomedical purposes. We modified CNCs with β-cyclodextrin (CNCs-β-CD), with N -(2-aminoethylmethacrylamide) (CNCs-AEMA1), and with N -isopropylacrylamide (CNCs-NIPAAm), designed for delivery of lipophilic, anionic and thermo-responsive drugs, respectively. We also synthesized CNCs-grafted with the monomer 2-methacryloyloxyethylphosphorylcholine (MPC), which can mimic the phospholipid polar groups within cell membranes, making it suitable for coating cardiovascular stents. We evaluated the immunological response of these nanomaterials by assessing NLRP3 inflammasome signaling pathway (ELISA and western blotting) and oxidative stress by analyzing mitochondrial ROS and protein S-glutathionylation (PSSG) in mouse (J774A.1) and human (THP-1) myeloid cells as well in human peripheral mononuclear blood cells (PMBCs). In summary, we found that the both CNCs-β-CD and CNCs-MPC had a tendency to decrease IL-1β secretion in LPS-stimulated cell lines and also in non-stimulated PMBCs. Mitochondrial ROS was elevated with all nanomaterial in non-stimulated J774A.1 cells. LPS-stimulated J774A.1 cells treated with CNCs-MPC mitochondrial ROS and PSSG were both decreased. Overall our results indicated that different modification on the surface of CNCs indeed affect their biomedical properties and also can cause undesirable effects. Therefore, further and more in depth interdisciplinary studies are necessary to fully understand and explore the potential biomedical applicability of CNCs. [ABSTRACT FROM AUTHOR]

Recently we have demonstrated that needle-like, cellulose-based nanomaterials, such as cationic derivatives of cellulose nanocrystals (CNCs, CNC-AEMA2) evoke immunological responses through NLRP3 inflammasome/IL-1β inflammatory pathway. We also previously demonstrated that curcumin, a naturally occurring polyphenolic compound isolated from Curcuma longa (Zingiberaceae), was able to suppress, at least in part, this immunological response, as observed by diminished IL-1β secretion in LPS/CNC-AEMA2-stimulated macrophages. These results are not a totally surprise because curcumin is a well-known antioxidant and antinflammatory natural compound. In addition to acting as “scavenger” of reactive oxygen species (ROS), several studies indicate that curcumin also upregulates antioxidant enzymes by activating the Nfr2 signaling pathway. However, the mechanisms by which this natural compound exerts its protective activity is still under investigation. We hypothesize that curcumin may also affect the redox status, such as S-glutathionylation, of key proteins involved in the NLRP3 inflammasome/IL-1β pathway, and therefore impacts their protein-protein interactions. The goal of this study was to investigate the effects of curcumin on the S-glutathionylation of NLRP3 induced by CNC-AEMA2 in LPS-primed mouse macrophages (J774A.1), as well as interactions among proteins of the NLRP3 inflammasome complex using immunoprecipitation and Western blot techniques. Cells were primed for 4h with lipopolysaccharide (LPS) in presence or absence of curcumin, and CNC-AEMA2 was added for another 20h. Our main finding indicates that the addition of curcumin concomitantly with LPS caused the greatest decrease in NLRP3 and increase in caspase-1 S-glutathionylation, which appears to favor protein-protein interactions in the NLRP3 complex. Taking together our results suggest that, at least in part, the antinflammatory activity of curcumin is associated with changes in S-glutathionylation of key NLRP3 inflammasome components, and perhaps resulting in sustained complex assembly and suppression of IL-1β secretion. [ABSTRACT FROM AUTHOR]