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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.
Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Sreejesh Sreedharan, Georgios Zouganelis, Samantha J Drake, Gyanendra Tripathi, Ali Kermanizadeh
Ko et al. (2020) examined the potential toxic effects of SiO2 NMs (primary size approximately 50 nm and aggregates of approximately 440 nm) in an OVA-sensitized asthmatic mice model. In these trials, 6-week-old- female BALB/c mice were divided into different treatment groups: vehicle control, OVA sensitization only, healthy mice exposed to materials and sensitized animals exposed to NMs. The material exposed animals received the SiO2 via intranasal instillation at doses of 5, 10 or 20 mg/kg on three occasions every other day over a 5-day period. Mice exposed to SiO2 NMs in the diseased animals displayed the highest and significant inflammatory cell counts mostly notable for eosinophil total cell counts, IL1ß, IL5, IL6, IL13 and TNF-α levels, mucus secretion and nucleotide-binding and oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) levels which were well above the other treatment groups. Evidence indicates that NMs adverse effects are aggravated in the asthma models compared to the healthy animals (Ko et al. 2020).
Crystal structure and protective effect in osteoarthritis of Co(II)-mediated pyridinium-bearing coordination polymer
Published in Journal of Coordination Chemistry, 2019
Wei He, Qinghui Yuan, Haibo Zeng
In this study, we prepared a new Co(II) pyridinium-bearing coordination polymer, {[Co(BCbpe)(ipa)]·3H2O}n (1), along with its nanosheets (denoted as nano 1 hereafter) via the solvothermal method and green grinding method, respectively. To evaluate the protective activity of the nano-structure of 1 in osteoarthritis, the post-traumatic OA model was constructed, followed by compound treatment [17]. ELISA results indicated that compound treatment significantly reduced the inflammatory level in OA rats. The RT-PCR results suggested inhibitory effect of 1 on inflammatory level of OA rats, owing to its inhabitation on NLR family, pyrin domain containing 3 (nlrp3), caspase-1 and il-1β gene expression. Molecular docking analysis of the complex indicated that the proposed drug candidate showed desirable drug-like criteria. Thus 1 is an excellent candidate for OA therapy.
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.