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Fenugreek in Management of Immunological, Infectious, and Malignant Disorders
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Rohini Pujari, Prasad Thakurdesai
The study in another fish, juvenile blunt snout bream (Megalobrama amblycephala), supports the efficacy of fenugreek seed extracts to protect against oxidative stress and inflammation without affecting growth, development, and immune response (Yu et al. 2019). In this study, the fenugreek seed extract (0.04%, 0.08%, and 0.16% in diet for eight weeks) significantly lowered the lipid content, immunoglobulin M (IgM), plasma complement component 3 (C3), total protein (TP), and albumin (ALB) levels and reduced the relative expressions of fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), and sterol regulatory element-binding protein-1 (SREBP1) mRNA in the fish liver. Furthermore, fenugreek seed extract diet showed reduced pro-inflammatory genes expressions by regulating interleukin 8 (IL-8) mRNA levels and tumor necrosis factor-α (TNF-α) and kelch-like ECH-associated protein 1 (Keap1) and enhanced the expressions of anti-inflammatory genes by regulating transforming growth factor (TGF-β) and interleukin 10 (IL-10), the target of rapamycin (TOR), S6 kinase-polypeptide 1 (S6K1) and growth factor-1 (IGF-1), glutathione peroxidase-1 (GPx1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Dietary Fenugreek seed extract showed antioxidant properties without any effect on specific growth rate (SGR), feed conversion ratio (FCR), weight gain (WG), and final weight (FW) (Yu et al. 2019).
Mite allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Enrique Fernández-Caldas, Leonardo Puerta, Luis Caraballo, Victor Iraola, Richard F. Lockey
As the complex nature of IgE synthesis became more evident, the discovery of “beyond MHC” immune response genes influencing IgE was more frequent. Polymorphisms in Th2 genes, for instance, those in the gene encoding interleukin 4 at the 5q31 locus [257,258] and the signal transducer and activator of transcription 6 (STAT6) [259], have been replicated in different populations. Associations with mite sensitization also have been reported with polymorphisms in the genes encoding interleukin-18 (IL-18) [260,261], leukotriene C4 synthase (LTC4S) [262], nitric oxide synthase 1 (NOS1) [263], interleukin-4 receptor alpha (ILR4A) [257], dendritic cell associated nuclear protein 1 (DCNP1) [264], interferon regulatory factor 1 (IRF-1) [265], CD14 [266,267], Janus kinase 2 (JAK2), GATA binding protein 3 (GATA3), CD40, and interleukin-5 receptor alpha (IL5RA) [268], all of them participating in any of the multiple steps of IgE synthesis. The significant associations with polymorphisms in innate immune genes suggest that genetic effects exert their influences at very early phases of the response. These loci include the complement component 3 (C3) associated with the specific IgE levels to D. pteronyssinus [269], the myeloid differentiation factor 2 (MD2) associated with the specific IgE levels to D. pteronyssinus and Der p 2 [270], and the nucleotide-binding oligomerization domain containing 1 (NOD1) associated with mite sensitization [268].
B cell targeting by molecular adjuvants for enhanced immunogenicity
Published in Expert Review of Vaccines, 2020
Taylor Sicard, Audrey Kassardjian, Jean-Philippe Julien
The complement system is essential for immune homeostasis and plays a critical role to bridge the innate and adaptive arms of the immune system. One critically important member of the complement system is C3d, which is derived from complement component 3 (C3) and results in C3d-tagged micro-organisms or antigens (reviewed in [71,72]) with the capacity to bind to complement receptor 2 (CR2 or CD21) on B cells and follicular dendritic cells for opsonization, as well as to assist in antigen presentation and the maintenance of immunological memory [73]. CD21 is typically found on the surface of B cells in association with CD19 and CD81 [74,75] and plays an integral role in immune regulation (reviewed in [76,77]). While CD21 itself does not have a signaling motif, binding of CD21 to C3d results in downstream signaling through the immunoreceptor tyrosine-based activation motifs (ITAMs) on CD19, resulting in improved B cell survival and proliferation [78–80]. When C3d-tagged pathogens simultaneously interact with CD21 and the BCR, pathway crosstalk decreases the signal threshold of antigen required to trigger B cell activation [81]. This pathway crosstalk is also capable of reducing inhibitory signals and preventing apoptosis, which are important factors for the induction of immunological memory.
Delivery of toll-like receptor agonists by complement C3-targeted liposomes activates immune cells and reduces tumour growth
Published in Journal of Drug Targeting, 2021
Alexandra Francian, Ashley Widmer, Troy Olsson, Marisabel Ramirez, Darion Heald, Keaton Rasic, Luke Adams, Holly Martinson, Max Kullberg
Our lab has developed a liposome nanoparticle targeted to myeloid cells, specifically APCs [12]. These liposomes are bound to complement component 3 (C3), a central member of the complement system, which works alongside the innate immune system in the initial defense against pathogens. C3 actively binds to and coats foreign particles, priming them for uptake into myeloid cells through the complement receptors. Previous publications from our lab have described the formulation, targeting specificity, and usage of these C3-liposomes to deliver antigens directly to APCs in order to increase antigen presentation to effector cells [13–15]. While having a specific immunogenic tumour antigen is ideal for cancer treatment, there may not always be one readily available, depending on the cancer type, mutational burden, variability between cancers/patients, and availability/cost of sequencing patient samples. Therefore, this study aims to evaluate the use of C3-liposomes to deliver TLR agonist compounds, in the absence of specific tumour antigens, to activate APCs. We selected three TLR agonists, MPLA (recognised by TLR4), R848 (recognised by TLR7/8), and CpG 1826 (recognised by TLR9), based on their use in other cancer vaccine studies, their ability to activate innate immunity, and their ability to break immunosuppression and tolerance [16,17]. Furthermore, we utilised the 4T1 breast cancer mouse model, which is known to have tumours infiltrated with myeloid cells that are polarised towards tumour-associated macrophages and myeloid derived suppressor cells (TAMs and MDSCs, respectively) [18,19]. Using a combination of in vitro and in vivo experiments we tested the ability of C3-liposomes containing TLR agonists to activate APCs and induce tumour-specific adaptive immune responses.
Interactions among different genetic loci in age-related macular degeneration
Published in Ophthalmic Genetics, 2018
Mortaza Bonyadi, Mohammad Hossein Jabbarpoor Bonyadi, Mehdi Yaseri, Masoud Soheilian
Complement factor H (CFH) is a major regulatory plasma protein that efficiently controls the complement pathways. It regulates complement activation by possessing cofactor activity for the complement factor I mediated C3b inactivation (17,18). At the other hand, the alternative complement pathway is constantly activated at low levels by the tick-over of complement component 3 (18).