Search Results (893)

Nucleated erythroid cells (NECs) are emerging as important immunoregulators at the feto–maternal interface, yet their chemokine profiles and functional dynamics across pregnancy remain poorly understood. Using a murine allogeneic pregnancy model (CBA × C57Bl/6), we isolated placental and splenic TER-119⁺ NECs at mid- (E12.5) and late (E19.5) gestation. Chemokine production (13-plex), chemokine receptor expression (qPCR), immunosuppressive molecules (PD-L1, TGF-β, and ROS), T-cell proliferation (CFSE), and immune cell migration (Transwell) were assessed. CD45⁺ placental NECs were the main producers of PD-L1, TGF-β, and ROS, with maximal expression at E19.5, suggesting their potential contribution to the immunosuppressive functions observed in the total TER-119⁺ population. Chemokine production showed a striking shift in CCL17 and CXCL9 from the spleen to the placenta as pregnancy advanced (E12.5 → E19.5). Splenic NECs displayed dominant expressions of CCR3 and CXCR4. Unexpectedly, CCL2 and CCL4 blockade enhanced immune cell migration toward placental NECs at E19.5. Placental nucleated erythroid cells potently suppressed T-cell proliferation at E12.5, and this suppressive capacity remained stable until full term. Placental NECs undergo dynamic chemokine reprogramming while maintaining stable T-cell suppression. The paradoxical enhancement of migration after CCL2/CCL4 blockade suggests a complex chemokine network warranting further investigation. These findings provide new insights into the immunobiology of pregnancy and may have implications for understanding pregnancy complications. Full article

Anti-interferon-γ (IFN-γ) autoantibody (AAb)-associated adult-onset immunodeficiency (AOID) is an emerging disorder in East Asian adults characterized by severe opportunistic infections despite negative HIV status. The mechanisms driving anti-IFN-γ AAb production remain unclear. This study investigated B-cell gene expression, serum cytokine profiles, associations with AAb levels, and IFN-γ genetic variations in AOID patients. A cross-sectional study was conducted in 63 AOID patients and 30 healthy controls at Chiang Mai University Hospital, Thailand. Patients were classified as active or inactive according to infection status. B-cell gene expression, serum cytokines, anti-IFN-γ Aabs levels, and IFN-γ polymorphisms were analyzed by quantitative PCR, multiplex assays, ELISA, and nucleotide sequencing, respectively. AOID patients exhibited increased PAX5 and BLIMP1 expression and reduced XBP1, BCL6, KRAS, and BAFF expression. Active patients had higher levels of TNF-α, IL-6, IL-17A, IL-10, IL-21, and more chemokines than inactive patients. AAb levels positively correlated with TNF-α, IL-6, and IL-10. Correlation analysis showed positive associations among PAX5, XBP1, and KRAS, and a negative association between BLIMP1 and BCL6. No significant IFN-γ sequence differences were identified within the analyzed transcript region. These findings suggest altered B-cell gene expression and inflammatory cytokine profiles in AOID, which may be associated with the immunological alterations observed in these patients and may provide insights into potential mechanisms underlying anti-IFN-γ AAb production. Full article

Pathogen–host interaction plays key roles in the pathogenesis of infectious diseases. The miR-183/96/182 cluster (miR-183C) is highly expressed in trigeminal ganglion (TG) sensory neurons (SNs) and modulates corneal response to Pseudomonas aeruginosa (PA) infection. To uncover the molecular mechanisms of miR-183C modulating the interactions of PA and TG SN, we employed the miR-183C conventional knockout (KO) or sensory neuron-specific (SNS) conditional (C)KO mouse models. Trigeminal ganglion (TG) SNs were isolated for neurite growth and branching analyses. Neuropeptide and chemokine production by TG SNs in response to PA infection was studied by ELISA assays. Key target genes of miR-183C were validated by target luciferase reporter assays. Our data showed that the total neurite length and number of branches per TG SN were decreased in the CKO vs. WT mice, and in the male vs. female WT mice. PA infection of TG SN induced the production and secretion of CX3CL1 and substance P (sP); this response was significantly enhanced in miR-183C KO vs. WT mice. Antagonists to Toll-like receptor (TLR)4 and/or formyl peptide receptor (FPR)1 inhibited PA-induced responses. Target luciferase reporter assays confirmed that genes encoding TLR4 and FPR1, as well as NRP1—a repulsive axon guidance receptor, TAC1—the precursor gene of sP, CX3CL1 and ADAM10, a metalloproteinase involved in the production of soluble CX3CL1, were direct targets of miR-183C. These data suggest that PA directly activates TG SNs and induces chemokine and neuropeptide production/secretion through interactions with TLR4 and FPR1. miR-183C modulates this process by targeting a collection of key genes involved in axon guidance/projection, chemokine and neuropeptide biogenesis and receptors mediating PA-induced activation. Full article

Multidrug-resistant (MDR) Salmonella Typhimurium, largely spread through poultry products, increasingly resists antibiotic treatment. We evaluated dietary pomegranate peel extract-loaded nano-emulsions (PomNEs) on performance, immunity, antioxidant capacity, and S. Typhimurium resistance in laying hens. A total of 250 15-week-old Hy-Line Brown hens received a basal diet or diets supplemented with PomNEs at 0.3, 0.6, or 1.2 g/kg, and then were challenged with S. Typhimurium at 34 weeks. Hens fed PomNEs, especially PomNEs1.2, showed improved egg production and feed efficiency before challenge and restored normal output afterward. Supplementation reduced Salmonella colonization in the ovaries, liver, and eggs, with considerable reduction in eggs and ovaries at the highest dose by ten weeks, and down-regulated bacterial virulence genes (hilA, invA). Immune function improved through higher phagocytic activity, intracellular killing, and lysozyme levels, lower nitric oxide, up-regulated IgA and β-defensins (AvBD6, AvBD12), and suppressed pro-inflammatory cytokines and chemokines. Intestinal and ovarian redox balance improved via reduced COX2 and elevated GPX-1, HO-1, NQO1, SOD-1, and CAT expression. These benefits support PomNEs as promising natural feed additives to enhance laying performance, antioxidant defense, and immunity against salmonellosis, offering a sustainable strategy for supporting disease control in poultry production. Full article

Background: Cancer cells live in a dynamic and favorable ecosystem conducive to their growth and survival, known as the tumor microenvironment (TME). The TME is replete with various proinflammatory cell types that mediate crosstalk via the secretion of cytokines and chemokines to facilitate tumor growth and development. One cardinal proinflammatory cytokine that is present in the TME is interleukin-1 (IL-1). IL-1 promotes tumor angiogenesis and cancer cell metastasis; thus IL-1 receptor antagonist (IL-1Ra) is of clinical interest. Our lab previously reported that chronic exposure to exogenous IL-1 can select for cancer cells that evolve insensitivity to IL-1 signaling, thus rendering IL-1-targeting therapies, like IL-1Ra, irrelevant. While immune cells are the primary source of TME IL-1, cancer cells can also produce and secrete IL-1 to engage in autocrine and/or paracrine signaling. In this context, cancer cell exposure to multiple other sources of exogenous IL-1 beyond autocrine production might also amplify extrinsic IL-1 signaling in these cells, but the consequences of sustained amplified IL-1 signaling on the regulation, function, and therapeutic response of these cancer cells need to be explored. Methods: Using the IL-1-secreting 5637 bladder cancer (BlCa) cell line, we generated chronic IL-1 sublines by spiking the growth medium with additional IL-1α or IL-1β chronically for 6 months. Once established, we assessed subline acute IL-1 sensitivity, paracrine signaling and response to IL-1Ra. Results: Following chronic exposure to elevated exogenous IL-1 levels, the 5637 BlCa cell line retains sensitivity to acute IL-1 and IL-1Ra and maintains the ability to induce IL-1-dependent endothelial cell activation, which is reversed with IL-1Ra. These data suggest that for cancer cells that engage in cell autonomous IL-1 signaling, sustained extrinsic IL-1 exposure does not dampen IL-1 or IL-1Ra sensitivity, supporting the context-dependent use of IL-1 antagonists as rational therapeutics in both acute and chronic inflammatory TMEs. Full article

Donor liver scarcity is exacerbated by preservation-related injury, particularly ischemia-reperfusion injury (IRI), which reduces organ utilization and increases discard rates. Liver sinusoidal endothelial cells (LSECs) play a critical role in mediating IRI, yet their response to static cold storage (SCS) remains poorly understood. Here, we investigate the impact of SCS on isolated rat LSECs. Isolated rat hepatocytes, stellate cells, Kupffer cells, and LSECs were subjected to up to 3 days of SCS followed by up to 2 days of recovery, with LSECs also receiving apoptosis and/or oxidative stress inhibition. Afterwards, changes in survivability, functionality, and morphology were measured. Additionally, changes in gene, cytokine, and chemokine expression were also measured. We found that SCS reduced cell viability by approximately 40%, accompanied by a 60% reduction in metabolic activity and ATP levels, indicating substantial impairment in cellular energetics. SCS also doubled reactive oxygen species (ROS) production and upregulated oxidative stress and apoptosis-related genes, leading to functional decline in LSECs. Importantly, combined inhibition of apoptosis and oxidative stress improved LSEC viability by 20% and metabolic activity and ATP levels by 30% and 40%, respectively, and reduced ROS production by 50%. These findings highlight LSEC vulnerability to preservation injury and the importance of understanding LSEC-specific injury mechanisms to provide a foundation for the development of endothelial-targeted preservation strategies to significantly improve liver transplantation outcomes, subsequently increasing access to this life-saving treatment. Full article

Sjögren’s disease (SjD) is a chronic autoimmune disease characterized by lymphocytic infiltration and dysfunction of the exocrine glands, with manifestations extending beyond glandular sicca symptoms to multiple extraglandular systems. Although the pathogenesis of SjD remains incompletely understood, growing evidence indicates that a complex cytokine network involving both innate and adaptive immune pathways plays a central role in disease development. This narrative review summarizes recent updates on cytokine signaling in SjD across three clinically relevant domains. In glandular inflammation, activation of salivary gland epithelial cells through Toll-like receptor pathways triggers type I interferon (IFN) signaling via plasmacytoid dendritic cells, while IFN-γ, Th17-related cytokines (IL-6, IL-17, IL-22), BAFF/APRIL, and chemokines (CXCL10, CXCL12, CXCL13) collectively sustain local inflammation and ectopic lymphoid organization. The BAFF/APRIL axis, a systemic type I IFN signature, and IL-21–follicular helper T cell–B cell interactions primarily drive systemic immune activation, which together underlie autoantibody production, hypergammaglobulinemia, and a lymphoma-prone phenotype. In contrast, constitutional symptoms such as fatigue, pain, and dryness frequently dissociate from classical inflammatory activity and are better explained by neuroimmune–metabolic mechanisms, including the IFN-γ–IDO–kynurenine pathway and symptom-associated proteomic signatures. Collectively, these findings underscore the heterogeneous nature of SjD, in which glandular inflammation, systemic immune activation, and constitutional symptoms are driven by distinct yet partially overlapping cytokine pathways. Recognizing this heterogeneity has direct implications for cytokine-targeted therapy, suggesting that future trials should stratify patients by disease phenotype (IFN-high, B cell-dominant, and symptom-dominant) rather than treating SjD as a uniform population. Full article

Probiotic strains with multifunctional skin-beneficial properties represent promising candidates for next-generation cosmetic ingredients. In this study, a systematic stepwise screening strategy was applied to an in-house bacterial library comprising 302 isolates to identify candidates with antioxidant, anti-inflammatory, antimicrobial, wound-healing, and skin barrier-supportive activities. From this library, 33 strains were selected based on preliminary assessments and subjected to comprehensive in vitro evaluation. Cell viability and cytotoxicity assays confirmed the safety of all selected strains in RAW264.7 macrophages and HaCaT keratinocytes. Several strains exhibited strong DPPH radical scavenging activity and significantly inhibited nitric oxide production in LPS-stimulated macrophages. Among the selected candidates, Lacticaseibacillus rhamnosus DM073 demonstrated the most potent anti-inflammatory activity, whereas Lactiplantibacillus plantarum DM043 exhibited the greatest wound-healing capacity. All five selected strains displayed antimicrobial activity against Cutibacterium acnes. Furthermore, selected strains, particularly Lactiplantibacillus plantarum DM175 and Ligilactobacillus salivarius DM079, enhanced the expression of skin barrier-related genes, including zonula occludens-1 (ZO-1), occludin (OCLN), claudin-1 (Cla-1), and filaggrin (FLG), and partially restored their expression under TNF-α/IFN-γ-induced inflammatory conditions. Selected strains also reduced the expression of inflammatory chemokines in stimulated keratinocytes. Collectively, these findings demonstrate that the selected probiotic strains possess complementary multifunctional activities associated with skin health. In particular, DM073 exhibited superior anti-inflammatory activity, DM043 showed strong wound-healing potential, and DM175 demonstrated remarkable skin barrier-supportive effects. These strain-specific properties support their potential application in the development of probiotic-derived postbiotic cosmetic ingredients for skin soothing, barrier reinforcement, skin recovery, and microbiome-friendly skincare formulations. Further studies are warranted to evaluate their efficacy and safety in advanced skin models and clinical cosmetic applications. Full article

Background/Objectives: Watercress (Nasturtium officinale), a cruciferous vegetable rich in phenethyl isothiocyanate (PEITC) and bioactive phytochemicals, has demonstrated anti-inflammatory and cytoprotective activities in multiple disease models; however, its effects on colitis remain insufficiently characterized. In the present study, we investigated the effects of watercress extract supplementation in dextran sulfate sodium (DSS)-induced experimental colitis. Methods: Male C57BL/6 mice were fed either a standard AIN-93G diet or a diet supplemented with 0.5% (w/w) watercress extract for 4 weeks, followed by DSS administration to induce acute colitis. Colonic histopathological injury, immune responses, barrier integrity, and gut microbiota composition were evaluated. In addition, the activity of PEITC, a major bioactive constituent of watercress, was examined in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in vitro. Results: Watercress extract attenuated DSS-induced colon shortening and reduced histopathological injury. The supplementation of watercress extract also decreased colonic immune cell accumulation, suppressed the expression of pro-inflammatory mediators, and preserved intestinal barrier integrity. The 16S rRNA gene amplicon sequencing further revealed that watercress extract reshaped gut microbial composition, including increased abundance of Monoglobus and Adlercreutzia, and reduced abundance of microbial taxa such as Enterococcus and Enterorhabdus. Moreover, PEITC suppressed LPS-induced inflammatory activation in RAW264.7 macrophages by reducing nitric oxide production, inhibiting p38 MAPK phosphorylation, and downregulating multiple inflammatory cytokines and chemokines. Conclusions: These findings demonstrate that watercress extract alleviates experimental colitis through attenuating mucosal inflammation, preserving intestinal barrier function, and modulating the gut microbiota, highlighting watercress as a promising dietary strategy for improving gut health and mitigating intestinal inflammation. Full article

Twenty-seven cytochalasans, including thirteen previously undescribed analogs with a 5/6/6/6 tetracyclic skeleton (curtachalasins Y1–Y13), were isolated from the rice-based culture of a soil-derived fungus, Xylaria sp. Y01. Their structures were determined through comprehensive analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-stimulated RAW264.7 macrophages. Curtachalasin Y1 (12), 5,6-dihydro-7-oxo-18-desoxy-19,20-epoxycytochalasin C (21), and 7-oxo-19,20-epoxycytochalasin C (22) exhibited potent inhibition, with IC₅₀ values of 55.4, 43.8, and 17.8 µM, respectively, compared to 14.9 μM for the positive control dexamethasone. Furthermore, these compounds suppressed lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines IL-6, MCP-1, and TNF-α, confirming their anti-inflammatory activity. Preliminary mechanistic investigation indicated that compound 22 exerts its anti-inflammatory effects in RAW264.7 cells by downregulating CXC motif chemokine ligand 10 (CXCL10) and upregulating suppressor of cytokine signaling 3 (SOCS3) expression. These results expand the structural diversity of cytochalasans from Xylaria species and provide a basis for further exploration of their anti-inflammatory potential. Full article

Micro-fragmented adipose tissue (mFAT) is a promising autologous biologic in regenerative medicine because it provides a mechanically processed adipose-derived product that preserves native extracellular matrix architecture and a cellular milieu rich in mesenchymal stem cells, pericytes, growth factors, cytokines, and extracellular vesicles. Mechanistically, mFAT is hypothesized to act largely through paracrine signaling that dampens inflammation, supports vascular stabilization, and promotes cartilage and soft-tissue repair; in vitro data suggest modulation of osteoarthritic synovial macrophage signaling, including reductions in chemokines such as CCL2 and CCL3. Preparation involves liposuction harvest followed by closed, sterile mechanical processing without enzymatic digestion or cell expansion, aligning with “minimal manipulation” concepts relevant to regulatory frameworks. Preclinical animal studies generally demonstrate favorable effects on synovial inflammation and cartilage matrix markers (e.g., glycosaminoglycan content) with limited adverse events. Clinically, the strongest body of evidence is in knee osteoarthritis, where multiple prospective and retrospective studies report improvements in pain and function from months to several years after single injections, though response rates vary and study designs are heterogeneous. Evolving data support potential benefit in hip osteoarthritis and select tendon conditions, but cohorts remain small. Overall, mFAT appears safe and potentially effective, yet larger, standardized, long-term randomized controlled trials and comparative studies versus platelet-rich plasma and bone marrow aspirate concentrates are needed to clarify indications, dosing, durability, and mechanisms in vivo. Full article

Atopic dermatitis (AD) is a chronic skin disorder driven by Th2 immune dysregulation, persistent inflammation, and epidermal barrier defects. Oxidative stress acts as a major upstream factor in this process, amplifying inflammatory signals and worsening disease severity. While current treatments relieve acute symptoms, long-term application is often constrained by side effects and poor barrier restoration, pointing to a need for safer, multifaceted alternatives. Here, we formulated a complex of Torilis japonica extract (TJE) and GHK-Cu (Glycyl-L-histidyl-L-lysine copper(II)) complex and examined its anti-atopic and skin-regenerative properties using a TNF-α (Tumor necrosis factor-α)/IFN-γ (Interferon-γ)-stimulated HaCaT cell model. TJE decreased the expression of AD-related chemokines (TARC(Thymus and activation-regulated chemokine (CCL17)) and CTACK(Cutaneous T-cell-attracting chemokine (CCL27)) as well as IgE production, confirming the suppression of Th2-driven inflammation. An optimized 6:4 ratio (TJE:GHK-Cu) yielded the highest efficacy compared to individual treatments, indicating a synergistic interaction. TJE–GHK-Cu complex suppressed the transcription of key Th2 cytokines (IL-4, IL-5, IL-10, and IL-13) and promoted keratinocyte migration during wound healing assays. The formulation also displayed strong radical scavenging activity without compromising cell viability. These results demonstrate that the TJE–GHK-Cu complex provides simultaneous anti-inflammatory, antioxidant, and regenerative benefits, presenting a formulation warranting further investigation for managing AD. Full article

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75% of renal cell carcinomas and is defined by near-universal VHL inactivation, leading to constitutive HIF stabilisation, metabolic reprogramming, and an immunologically distinct tumour microenvironment (TME). Although ccRCC is characterised by abundant immune infiltration, this paradoxically correlates with poor prognosis, reflecting a TME that imposes interconnected physical, immunological, and metabolic barriers to effective immunotherapy. Chimeric antigen receptor (CAR)-based therapies have revolutionised the treatment of haematological malignancies, but their translation to ccRCC has encountered substantial hurdles. The first-in-human trial targeting carbonic anhydrase IX (CAIX) was limited by on-target off-tumour toxicity and CAR immunogenicity—lessons that fundamentally reshaped the field. CD70 has since emerged as the dominant clinical target, expressed in over 80% of ccRCCs with a highly restricted normal tissue distribution. The phase I COBALT-RCC trial of CTX130, an allogeneic CRISPR-Cas9-edited CD70-directed CAR-T cell product, provided formal proof of concept, achieving disease control in 81.3% of heavily pretreated patients and a durable complete response now exceeding three years—the first such sustained remission reported for any CAR-T cell product in a solid malignancy. Nevertheless, the low frequency of durable responses and universal loss of CAR-T cell persistence by day 28 underscore that major barriers remain. Beyond CD70, the field has diversified across multiple platforms, including CAR–natural killer (NK) cells, CAR–natural killer T (NKT) cells, and CAR–macrophages, each offering distinct biological advantages. This review synthesises current knowledge of the ccRCC TME, the preclinical landscape of CAR-based therapies, and emerging clinical evidence from more than 30 registered trials. We discuss target antigens; engineering strategies to overcome TME barriers, including cytokine armouring, chemokine receptor co-expression, switch receptors, and metabolic reprogramming; and rational combination approaches. We argue that the convergence of optimised target selection, cellular engineering, combination strategies, and biomarker-driven trial design may ultimately improve outcomes for patients with ccRCC. However, achieving a cure remains an aspirational goal, and significant barriers must first be overcome. Full article

Background/Objectives: Exposure to particulate matter (PM) containing bacterial endotoxins triggers inflammation and oxidative stress in the respiratory epithelium. In this study, we investigated chitosan nanoparticle-loaded Cordyceps militaris grown on germinated Rhynchosia nulubilis (GCN) as a potential functional food-derived ingredient against PM- and lipopolysaccharide (LPS)-induced cellular damage in human lung epithelial cells. Methods: This study employed an integrative approach combining GCN analysis with bioinformatics methods using a PM- and LPS-induced pulmonary cellular inflammation model. Gene Expression Omnibus (GEO) transcriptomic datasets and Cytoscape-based network analysis were utilized to identify key hub genes and signaling pathways associated with PM- and LPS-induced pulmonary inflammation, which were subsequently validated by RT-PCR and Western blotting. Results: Nano-encapsulation significantly improved the antioxidant capacity and storage stability of the extract compared with non-encapsulated Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC). GCN markedly attenuated PM- and LPS-induced cytotoxicity and intracellular reactive oxygen species (ROS) production in a dose-dependent manner, resulting in a therapeutic index approximately 4.5-fold higher than that of GRC under PM and LPS co-exposure. Bioinformatics analysis identified inflammation-related genes and pathways associated with PM- and LPS-induced pulmonary responses, primarily enriched in tumor necrosis factor (TNF)-related inflammatory pathways, Toll-like receptor signaling, and cytokine signaling. Consistent with these findings, GCN suppressed the expression of C-X-C motif chemokine ligand 2 (CXCL-2) and tumor necrosis factor-alpha (TNF-α) mRNA and inhibited mitogen-activated protein kinase (MAPK)-mediated activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) signaling pathways in human type II alveolar epithelial cells (A549). Conclusions: Collectively, nano-encapsulation enhanced the stability and bioactivity of Cordyceps militaris-based extracts, suggesting that GCN may have potential as a functional food-derived candidate ingredient to protect airway epithelial cells against inflammation and oxidative stress induced by PM and LPS. As this study was conducted using an in vitro A549 epithelial cell model, further validation in physiologically relevant systems is needed to confirm its translational applicability. Full article

Fucoidan, a sulfated polysaccharide, is known for its beneficial bioactive effects, for example antioxidant, anti-inflammatory, and vascular modulatory effects. Such a bioactive compound may also be useful for treating neurodegenerative diseases like age-related macular degeneration (AMD). Our research focuses on AMD-related pathomechanisms using primary porcine retinal pigment epithelium (RPE) cells in vitro and zebrafish (Danio rerio) models in vivo. We tested the bioactivity of a commercially available fucoidan (FVs) from bladderwrack with regard to pathomechanisms of AMD. We performed multiplex assays, RT-qPCR and fluorescence-based assays for the formation of nitric oxide (DAF-FM assay) and reactive oxygen species (DCF-DA assay) to analyze angiogenesis-related chemokines and pro-inflammatory cytokines as well as protection against oxidative stress and inflammatory insult. Our results showed that FVs significantly reduced the secretion of pro-angiogenic vascular endothelial growth factor A (VEGF-A) and follistatin as well as the pro-inflammatory cytokines interleukin 8 (IL-8) after lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC) induction. Interleukin 6 (IL-6) was also reduced in the supernatant of the RPE cells. Additionally, in zebrafish, fucoidan decreased the production of NO and ROS. Gene expression of zebrafish embryos revealed anti-inflammatory effects by suppressing pro-inflammatory genes and significantly downregulating, e.g., interleukin 1 beta (IL-1β). These findings indicate modulation of oxidative stress, inflammatory responses, and VEGF secretion of the used FVs. This study demonstrates that fucoidan possesses AMD-relevant bioactivities in vitro and in vivo, suggesting fucoidan warrants further investigation in AMD-related research and related pathological mechanisms. Full article