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Nanotoxicology and Regulatory Aspects of Nanomaterials and Nanomedicines
Published in Yasser Shahzad, Syed A.A. Rizvi, Abid Mehmood Yousaf, Talib Hussain, Drug Delivery Using Nanomaterials, 2022
Upon macrophage recognition and phagocytosis, inflammatory mediators are released, which initiate an inflammatory response. This is a physio-pathological reaction which in excess or persistence of inflammation could predispose to autoimmune disease, long-term diseases, and cancer (Donahue et al., 2019). When the macrophages are overwhelmed by NP size, shape, chemistry, particle number, and agglomerates or surface group with prolonged pulmonary retention due to slow or incomplete degradation and metabolism, inflammatory response will be evoked. It has been known from the pathogenesis of lung silicosis that long fibers were trapped longer due to defective clearance with subsequent inflammatory induction. Hence, the multiple parameters of NPs physicochemical characteristics play a role in inflammation induction (Braakhuis et al., 2014). Amorphous silica NP induce inflammation and cell death with generation of ROS (Fu et al., 2014). A new potential mechanism involved in the inflammation cascades is the NLRP3 inflammasome activation with rising IL-1β. Certain pathogens, toxins or particles might induce this mechanism with a rise of the IL-1β through activation of caspase 1 and initiation of inflammatory induced apoptosis or known as pyroptosis. Several studies has showed NPs can induce the NLRP3 activation, e.g., some liposomes and polymer-based NPs. A detailed source for this mechanism and its assessment can be found in these following sources (Sharma et al., 2018; Shirasuna et al., 2019).
Immunotherapy and Vaccines
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Johanna Poecheim, Gerrit Borchard
The adjuvant properties of chitosan, a biodegradable biopolymer, have also been subjected to investigations. Chitosan potently activated the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome (a multiprotein oligomer that is a component of the innate immune system) in a phagocytosis-dependent manner. Chitosan is the deacetylated derivative of chitin, which was shown to be relatively inert, suggesting the influence of charge on the immunostimulatory properties of chitosan because of the presence of a secondary amino group (Bueter et al., 2011). Also Tokura et al., who studied the immunological aspects of chitin and chitin derivatives administered to animals, pointed out that chitosan itself, as an adjuvant, can induce polarized Th2 responses (Borchard et al., 2012; Tokura et al., 1999). Whether this activation is based on the interaction of chitosan with PRRs in a lectin-like fashion is still under discussion.
A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma
Published in Journal of Toxicology and Environmental Health, Part A, 2018
S. Crovella, RR. Moura, S. Cappellani, F. Celsi, E. Trevisan, M. Schneider, A. Brollo, EM. Nicastro, F. Vita, L. Finotto, G. Zabucchi, V. Borelli
Two of the major malignant diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (Andujar et al. 2016; Gilham et al. 2016; Lemen 2016). The mechanisms of injury to cells of the lung and pleura as well as disease development by these pathogenic particulates are unclear (Kamp and Weitzman 1999; Mossman et al. 1990). Inflammation, a hallmark of exposure to asbestos, was observed both in animal models and in lungs of patients with asbestos-related lung disease (Mossman et al. 1990; Mossman and Churg 1998). Bronchial epithelial cells and alveolar macrophages are in prolonged contact with the inhaled asbestos fibers when clearing them from the lung, and might initiate and sustain inflammatory responses. NLRP1 and NLRP3 proteins are known to play a crucial role in assembling the inflammasome, resulting in the processing of proinflammatory cytokines IL-1β and IL-18 (Kummer et al. 2007).
Diagnosis and management of implant debris-associated inflammation
Published in Expert Review of Medical Devices, 2020
Stuart B. Goodman, Jiri Gallo, Emmanuel Gibon, Michiaki Takagi
The role of innate-immune sensors is presently a topic of great interest in inflammation research. Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) can recognize not only exogenous pathogen-associated molecular pattern (PAMPs) but also endogenous molecules created upon tissue remodeling and inflammation. Thus, these substances can augment the local host response. Indeed, marked immunoreactivity of TLR1, TLR2, TLR5, TLR6, and TLR9 molecules was mainly detected in monocytes/macrophages and occasionally in neighboring stromal cells; the presence of these molecules paralleled their upregulation at messenger RNA levels in the aseptic foreign body granuloma around implants. NLRs and their related molecules, namely NLRP (Nacht, leucine-rich repeat and pyrin domain-containing protein) 3, caspase-1, and apoptosis-associated speckle-like protein containing caspase recruitment domain (ASC), were also found in the foreign body granuloma [35,63]. TLRs can sense not only endogenous molecule of microbial origin, but also endogenous products relating to inflammation, such as heat-shock proteins, high mobility group box (HMGB)1, fibronectin, and hyaluronic acid. NLRP3 can be activated by adenosine triphosphate (ATP), radical oxygen species (ROS), and uric acid released from damaged cells. Cellular debris and products relating to foreign body reaction can stimulate these sensors [63]. In addition, endogenous products, as well as exogenous microbial molecules, can attach to surfaces of wear debris, which can also enhance the cellular response, after phagocytosis of the particles. Thus, the distinction between aseptic and septic conditions in particle-laden periprosthetic joint inflammation is still somewhat unclear.
A new Co(II)-containing coordination polymer: treatment activity on sepsis mice by activating the NLRP3 inflammatory pathway
Published in Journal of Coordination Chemistry, 2021
Qian Xu, Yan-Lai Xiao, Xiao-Qing Su, Xiao-Bo Zhang, Zhuo-Jun Deng
Supramolecular structures involving metals in crystal engineering is a research hotspot in coordination and supramolecular chemistry. This field has attracted attention, not only because of their important architectures, but also because of their latent applications in biochemistry, catalysis and luminescence, especially in modern pharmaceutical chemistry [4–9]. Nitrogen-heterocyclic carboxylic acid ligands have received attention of biologists and chemists owing to their rich functional performances and coordination, along with their hydrogen-bonding receptors and donors in solution [10–12]. Cobalt is of biological interest because of its role in the active center of vitamin B12, which regulates indirectly the synthesis of DNA. Additionally, there are at least eight cobalt-dependent proteins. Cobalt is also involved in the co-enzyme of vitamin B12 and is used as a supplement of the vitamin. Since the first reported studies on the biological activity of Co complexes in 1952, many cobalt complexes of biological interest have been reported with the most structurally characterized showing antitumor, antiproliferative, antimicrobial and antifungal activities [13–17]. In our current experiment, solvothermal reaction between H4L, a rigid 2,6-di(2′,5′-dicarboxylphenyl)pyridine ligand, and Co(NO3)2·6H2O in water and DMF solvent results in generation of a three-dimensional (3 D) coordination polymer (CP) on the basis of Co(II), [Co4(L)2(H2O)4]n·4DMF·H2O (scheme 1). The product is investigated with PXRD, thermogravimetric analyses, single crystal X-ray diffraction, EA and IR spectra. Furthermore, application of 1 against sepsis mice was evaluated and its specific mechanism is discussed. To validate the hypothesis from the experimental results regarding the origin of biological efficiency of 1, molecular docking was performed. This compound possesses the potential to be an outstanding candidate for treatment of sepsis through activating the inflammatory pathway of NLRP3.