International Flavors & Fragrances is an American corporation that creates and manufactures food, beverage, health & biosciences, scent and pharma solutions, and complementary adjacent products, including cosmetic active and natural health ingredients, which are used in a wide variety of consumer products. It is headquartered in New York City and has creative, sales, and manufacturing facilities in 45 different countries. The company is a member of the S&P 500 Index.
Spondyloarthritis (SpA) represents a heterogeneous group of chronic inflammatory rheumatologic diseases, including axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and SpA associated with inflammatory bowel disease (IBD). These conditions share overlapping clinical manifestations, genetic predisposition-particularly a strong association with HLA-B27-and common immunopathogenic pathways, notably the IL-23/IL-17 axis and tumor necrosis factor (TNF) signaling. Understanding SpA pathophysiology has been greatly facilitated by animal models, which have provided critical mechanistic insights and served as indispensable tools for preclinical drug testing. Among these, rodent models have been particularly informative. However, despite their contributions, no single model reproduces the full clinical spectrum of SpA, which includes axial inflammation, enthesitis, peripheral arthritis, and extra-articular manifestations such as uveitis, psoriasis, and gut involvement. This review provides a comprehensive analysis of rodent SpA models, focusing on their mechanistic underpinnings, key discoveries, and translational relevance. We first summarize the major categories of models before examining the strengths and limitations of each. We highlight how these models have advanced our understanding of the gut-joint axis, IL-23-driven entheseal inflammation, and TNF-dependent pathways, which are now major therapeutic targets. Finally, we discuss emerging strategies to enhance translational fidelity, including humanized mice, microbiome engineering, and integration of multi-omic approaches. These developments are essential to bridge the current gap between experimental findings and clinical applications in SpA.
Coordinated responses of intestinal epithelial and immune cells are essential for maintaining barrier integrity and immune homeostasis in dogs, yet our mechanistic understanding of probiotic-derived metabolites remains limited due to reliance on non-canine experimental models, highlighting the need for studies in canine-derived systems. Here, we investigated the effects of metabolites derived from Limosilactobacillus reuteri strain ATCC PTA6127 (Lr6127), delivered as a cell-free supernatant (CFS), on canine epithelial MCA-B1 cells and macrophage-like DH82 cells subjected to lipopolysaccharide (LPS)-induced inflammatory stress. Lr6127 CFS significantly reduced epithelial permeability, decreasing FITC-dextran leakage to 94.9 ± 1.9% (normalized relative to LPS-treated control, which was set as 100%) (p < 0.001), despite no detectable transcriptional changes in tight junction, adherens junction, or mucin genes. Barrier effects were instead associated with changes in markers of cellular stress responses, with heme oxygenase expression decreasing from 0.9 ± 0.1 to 0.7 ± 0.1 (p < 0.05). In DH82 immune cells, Lr6127-derived metabolites altered LPS-induced stress- and inflammation-related gene expression patterns; enhanced anti-apoptotic responses, as reflected by the increased BCL2 expression (1.4 ± 0.1 vs. 1.0 ± 0.0; p < 0.01) and elevated BCL2/BAX ratios (p < 0.01); and reduced expression of pro-inflammatory mediators including IL-6 and CCL2 (p < 0.05-0.001). Proteomic analysis corroborated that Lr6127-derived metabolites reduced the abundance of inflammatory and STAT-associated signaling proteins under LPS challenge, while indicating context-dependent changes in immune-related protein profiles under resting condition. Collectively, these results suggest that Lr6127-derived metabolites improved epithelial barrier function, which was accompanied by coordinated changes in cellular stress-related and inflammatory pathways, highlighting their potential to positively influence host responses.
Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major challenge to swine production worldwide. Current vaccines have limited efficacy against genetically diverse PRRSV strains. Therefore, strategies with alternative modes of action-such as antiviral approaches that target conserved virus-host interactions, including viral attachment and entry, rather than relying solely on adaptive immune responses-are needed. We first evaluated the in vitro effect of griffithsin (GRFT), a high-mannose-binding lectin, in the monkey kidney cell line MARC-145. Cells were pre-treated with GRFT (50-200 µg/mL) prior to PRRSV infection, after which cell morphology and viral RNA replication (measured by RT-qPCR) were assessed. Pre-treatment with 100-200 µg/mL GRFT, followed by PRRSV inoculation at a multiplicity of infection of 1 or 10, reduced viral replication in MARC145 cells in a dose-dependent manner, achieving almost 100% inhibition of ORF5 and ORF7 RNA compared with untreated controls (p < 0.0001). We next investigated the in vivo effects of intranasal GRFT administration (7.5 or 15 mg/day) in pigs (n = 56). Pigs treated with 15 mg/day GRFT exhibited significantly reduced (p < 0.05) viremia 2, 4 and 7 days post-challenge, compared with untreated, challenged, and controls (log10 8.1 ± 0.2 vs. 9.0 ± 0.25, 8.2 ± 0.1 vs. 9.1 ± 0.2, and 8.9 ± 0.2 vs. 9.3 ± 0.2, respectively), along with earlier resolution of fever and a trend toward increased average daily gain over 42 days (p < 0.1). These findings are the first report of GRFT efficacy in pigs and support its potential as an antiviral strategy against PRRSV, alongside existing interventions.
Abstract Background Cell envelope proteinases have long played a pivotal role in dairy science. However, as demand for alternative food sources grows, their application in plant-based food matrices is scarcely investigated. A deeper physiological and technological understanding of these enzymes requires efficient and effective tools tailored to this emerging sector. To date, plasmid-based recombination in Lactococcus spp. remains the most widely used and effective method. Results In this study, we engineered S. thermophilus LMD-9 as a host for heterologous expression of protease from Lc. cremoris . S. thermophilus LMD-9 offers several advantages, including its GRAS status, efficient chromosomal gene integration via natural competence, and native machinery for functional protease production, making it a highly versatile host. Previous attempts to employ this strain yielded inactive protease due to unresolved bottlenecks; here, we characterize and overcome those challenges to establish LMD-9 as a robust system for protease expression. Exploration of potential bottlenecks highlighted the availability of intrinsic peptidyl-prolyl cis / trans isomerase (PPIase; prtM / prsA ) as a key factor influencing successful enzyme expression. Three recombinant strains with genotypes: LMD-9 Δ prtS :: ermR , LMD-9 Δ prtS :: ermR —Ω prtP , and LMD-9 Δ prtS :: ermR —Ω ( prtM-prtP ), were generated to test the role of prtP -associated PPIase. Results demonstrated that inclusion of PrtP-specific PPIase from L. cremoris markedly enhances protease activity. In its absence, although partially compensated by the pleiotropic PPIase in S. thermophilus , we observed slower growth and reduced proteolytic activity. Conclusions These findings establish S. thermophilus LMD-9 as a robust chassis and alternative host for heterologous expression of cell envelope proteinases. To our knowledge, this is the first work to heterologously express active CEP enzyme in this host, and it highlights the role of PPIase availability as a key determinant of successful enzyme expression. This then provides a suitable and robust host for studying the application of CEPs in both dairy and emerging plant-based food applications.
