Proteomic insights into intestinal immune modulation in Atlantic salmon (Salmo salar) fed fucoidan from brown seaweed (Saccharina latissima).

A saponin-rich fraction of the roots from Cereus jamacaru (Cactaceae) has anti-inflammatory, antinociceptive and antipyretic effects in mice.

Gut microbiota dysbiosis and immune dysregulation are closely associated with the development of colorectal cancer. Identifying the mechanistic links among specific microbial species, metabolites, and immune responses is crucial for uncovering novel insights into its pathogenesis. Here we show, through metagenomic and metabolomic analyses of clinical cohorts, that Fusobacterium periodonticum is significantly enriched in colorectal cancer patients and strongly correlated with elevated decanoic acid levels. Single-cell transcriptomic results further reveal tissue-specific neutrophil enrichment in colorectal cancer tissues, characterized by high CXCL8 expression and activation of neutrophil-related immune pathways. Cellular experiments demonstrate that decanoic acid induces late apoptosis/necrosis of neutrophils, enhances their chemotaxis through a pertussis toxin-sensitive G-protein-dependent mechanism, and upregulates genes involved in leukocyte migration and tumorigenesis. Mouse models further confirm that F. periodonticum colonization increases intestinal dysplasia and decanoic acid levels, and that decanoic acid intervention promotes tumor progression by facilitating neutrophil infiltration and modulating the local immune microenvironment. Our study reveals an important role of F. periodonticum in colorectal tumorigenesis via decanoic acid-medicated neutrophil chemotaxis, providing mechanistic insights into the pathogenesis of colorectal cancer.

Leukocyte migration is a fundamental process in both innate and adaptive immune responses. This process is tightly regulated by chemokines and their cognate receptors. The bioavailability of chemokines is further modulated by atypical chemokine receptors (ACKRs), a subset of chemokine receptor-like molecules that lack coupling to canonical G protein-mediated signaling pathways. Among these, ACKR4 regulates dendritic cell migration through ligand scavenging and has been implicated in tumor progression in murine models. We previously established anti-mouse ACKR4 (mACKR4) mAbs, A4Mab-1, A4Mab-2, and A4Mab-3, by N-terminal peptide immunization. This study examined the binding epitopes of A4Mabs. Alanine (or glycine) scanning within the N-terminal region (amino acids 2-19) was performed using flow cytometry and Western blotting. Results showed that Tyr12 is required for recognition by A4Mab-1 in flow cytometry, whereas Tyr11, Tyr12, Glu14, Glu15, and Glu17 are required in Western blotting. For A4Mab-2, Tyr12, Glu15, and Asn16 are required in flow cytometry, whereas Tyr11, Tyr12, Tyr13, Glu15, and Asn16 are required in Western blotting. Additionally, Glu14, Asn16, and Glu17 are required for recognition by A4Mab-3 in flow cytometry. These findings contribute to the understanding of mACKR4 recognition by A4Mabs.

Natural products derived from medicinal plants represent an important source of bioactive compounds with potential therapeutic applications in the management of pain and inflammatory disorders. In this study, the chemical profile and pharmacological activities of the aqueous extract obtained from the fruit peel of Myrciaria floribunda (AeMf) were investigated. Chemical characterization was performed using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MSⁿ). The antinociceptive activity of AeMf was evaluated in mice using acetic acid-induced abdominal writhing, formalin, and tail immersion tests, while the anti-inflammatory potential was assessed through carrageenan-induced paw edema and peritonitis models. Chromatographic analysis revealed a chemical profile predominantly composed of organic acids and related metabolites, including quinic acid, citrate, maleate, and a fatty acid hexoside. In nociceptive models, AeMf produced a significant and dose-dependent reduction in acetic acid-induced writhing and markedly decreased paw-licking behavior in both phases of the formalin test. In addition, the extract increased tail withdrawal latency in the thermal nociception assay, indicating the involvement of both peripheral and central analgesic mechanisms. In inflammatory models, AeMf significantly inhibited carrageenan-induced paw edema, reduced leukocyte and neutrophil migration to the peritoneal cavity, and markedly suppressed the production of pro-inflammatory cytokines, including TNF-α and IL-1β. Collectively, these findings demonstrate that AeMf exerts potent antinociceptive and anti-inflammatory effects, likely mediated through the modulation of inflammatory mediators and cellular recruitment. The results highlight the therapeutic potential of Myrciaria floribunda as a promising natural source of bioactive compounds for the development of novel strategies for pain and inflammation management.

Harrisia adscendens (Gürke) Britton & Rose is traditionally used to manage kidney problems, fever, and pain. Despite its traditional use, its pharmacological properties remain underexplored. The hydroethanolic extract (HE) of its cladodes is of particular interest given its demonstrated safety and presence of acetophenones, phenolic acids, and flavonoids. The present study evaluated the antinociceptive, anti-inflammatory, antipyretic, and wound-healing activities of HE. HE was administered orally at 100, 200, or 400mg/kg to male mice. Nociceptive inhibition was measured through the acetic acid-triggered writhing, tail immersion, and formalin tests. The capacity to reduce inflammation was evaluated via carrageenan-induced paw edema and peritonitis. Antipyretic effects were measured after yeast-induced hyperthermia following HE administration. Wound-healing activity was assessed using topical gels containing 5% or 10% HE on dorsal wounds. HE at 200 and/or 400mg/kg markedly reduced abdominal writhing, paw-licking time in the formalin test, and increased latency in the tail immersion test. HE (200 and 400mg/kg) inhibited paw edema formation up to 47.5%, and reduced leukocyte migration in the peritonitis model. Levels of interleukins 2, 6 and 17 and TNF-α were decreased in the peritoneal fluid. HE induced a reduction in body temperature in the antipyretic assay. It also accelerated wound closure in the 10% formulation. HE exhibited antinociceptive, anti-inflammatory, antipyretic, and wound-healing activities, likely due to flavonoids, acetophenones, and phenolic acids. These effects may involve modulation of inflammatory mediators and immune cell activity.

Calcium oxalate (CaOx) nephrolithiasis is a recurrent urological disorder, and Randall's plaque (RP) of the renal papilla is widely accepted as an early site of stone nucleation. Although immune activation, epithelial injury, and extracellular matrix (ECM) remodeling have been reported in RP, the cell-type-specific transcriptional features of Epithelial Membrane Protein 1 (EMP1) in this tissue context remain undefined. A secondary, hypothesis-generating analysis of a publicly available single-cell RNA sequencing (scRNA-seq) dataset (NCBI GEO accession GSE176155; BioProject PRJNA735197) comprising renal papillary tissue from patients undergoing percutaneous nephrolithotomy for CaOx nephrolithiasis (RP samples) and matched normal renal papilla samples was performed. Raw FASTQ data were processed through Cell Ranger (v6.0.1) aligned to GRCh38, followed by quality control, normalization, dimensionality reduction (PCA, UMAP), graph-based clustering, and cell-type annotation in Seurat (v4.0.5) using canonical markers cross-checked against the Kidney Cell Atlas. Differential expression at the single-cell level was assessed by the Wilcoxon rank-sum test with Bonferroni correction. Coexpression, functional enrichment (GO, KEGG), and weighted gene coexpression network analysis (WGCNA) were used to characterise EMP1-associated transcriptional modules. Pseudobulk-style ANOVA and linear regression were performed as exploratory sensitivity checks at the sample level. At the single-cell level, EMP1 was significantly downregulated in RP-derived epithelial and stromal clusters compared with normal renal papilla (adjusted p < 0.01, log2FC ≤ -0.30). EMP1 was co-expressed with C3, RNASE1, NRG1, IFI16, S100A10, HSPA6, and FN1, and the EMP1-correlated module identified by WGCNA was negatively correlated with the RP phenotype (r = -0.72, p < 0.001). GO and KEGG enrichment showed associations with cell adhesion, integrin and heparin binding, leukocyte migration, neutrophil extracellular trap formation, and focal adhesion. Sample-level pseudobulk ANOVA and regression analyses did not reach statistical significance for most genes, consistent with the limited number of donors and the loss of cell-type resolution after pseudobulk aggregation; these results are presented as exploratory. This study reports an associative, hypothesis-generating link between reduced EMP1 expression in renal papillary epithelial and stromal populations and the molecular landscape of Randall's plaque. Independent transcriptomic, spatial, and functional validation will be required before EMP1 can be considered a candidate biomarker or therapeutic target in CaOx nephrolithiasis.

BackgroundInvasive mechanical ventilation (IMV) is a critical intervention for severe respiratory failure and has been widely used in the clinical management of COVID-19 patients. The relationship between such microbiota changes and the host transcriptome in IMV patients remains poorly documented.MethodsWe prospectively enrolled 69 critically ill COVID-19 patients, among whom 41 received IMV. Correlation analyses were conducted to investigate the relationship between the lung microbiome and host immune status in IMV COVID-19 patients.ResultsCompared to the Non-mechanical ventilation (NMV) group, patients in the IMV group exhibited significantly reduced alpha diversity, while no significant difference was observed in beta diversity. The abundance of Streptococcus genus was significantly higher in the NMV group, primarily dominated by Streptococcus oralis and Streptococcus mitis. Transcriptomic enrichment analysis revealed significant upregulation of inflammation-related pathways in the IMV group, including “positive regulation of inflammatory response” and “cellular response to interleukin-1”. The decreased relative abundance of Streptococcus genus in the IMV group showed significant correlations with upregulation of genes including CXCL8, PLAU, SELENOK, SDC4, RPL17, RPS23, TOMM7, and PLK3. These upregulated genes promoted the recruitment of immune cells to inflammatory sites through activation of pathways including chemotaxis, leukocyte migration, and leukocyte cell-cell adhesion, ultimately triggering a robust innate immune response.ConclusionIMV COVID-19 ARDS patients demonstrated significantly reduced pulmonary microbial diversity, with a marked decrease in the abundance of Streptococcus—primarily Streptococcus oralis and Streptococcus mitis. Transcriptomic profiling further revealed substantial upregulation of inflammatory pathways in IMV patients, including “positive regulation of inflammatory response”.

Immune tolerance: Parallels between pregnancy and kidney transplantation.

Type 1 diabetes (T1D) is characterised by destruction of pancreatic beta-cells by islet-infiltrating cytotoxic lymphocytes and elevated intra-islet secretion of pro-inflammatory cytokines. However, the underlying pathophysiological mechanisms remain incompletely understood. We hypothesised that abnormal elevation of islet NAD, via activation of NAMPT, plays a key role in driving islet autoimmune processes, leading to beta-cell death in T1D. Here, we report that NAMPT inhibition protects against pro-inflammatory cytokine (IL-1β, TNFα and IFNγ) mediated beta-cell dysfunction and apoptosis in isolated mouse and human islets. RNAseq revealed that NAMPT inhibition blocked cytokine-mediated gene expression linked to pro-inflammatory responses and leukocyte migration. In vivo, diabetes was induced in CD1 mice via multiple low-dose streptozotocin (MLDS) injections. MLDS mice were administered the NAMPT inhibitor FK866 (10 mg/kg; IP) or saline equivalent for 16 days. These experiments demonstrated that NAMPT inhibition improved glycaemic control and beta-cell survival and function in MLDS mice. FK866 also reduced proportions of islet-residing TNFα-producing CD4+T-cells and F4/80+macrophages, proliferation of spleen-derived CD4+ and CD8+T-cells and proliferation of islet-derived CD4+T-cells and F4/80+macrophages. Finally, we report that NAMPT inhibition was able to block pro-inflammatory cytokine-mediated migration of cytotoxic CD8+T-cells into isolated islets, using an in vitro transwell platform. This data supports a key immunomodulatory role for NAMPT in islet autoimmunity. NAMPT inhibition may be able to prevent beta-cell death and thus represent a novel therapeutic approach for T1D. The effects of increased NAD levels on islet inflammation require in-depth characterisation and caution should be exercised with regard to the use of NAD boosting supplements, particularly in individuals at risk of developing T1D.

BackgroundNeuroinflammation and blood–brain barrier (BBB) dysfunction are key contributors to the pathogenesis of many neurological disorders. Cannabinoid receptor 2 (CB2) agonists possess anti-inflammatory properties and may represent promising therapeutic agents for preserving BBB integrity. This study evaluated the effects of novel orally bioavailable CB2receptor agonists on leukocyte–endothelial interactions and BBB function usingin vitroandin vivomodels of neuroinflammation.MethodsNovel CB2receptor agonists were tested in an aseptic localized encephalitis mouse model and in a lipopolysaccharide (LPS)-induced systemic inflammatory response model. Leukocyte adhesion and migration within cerebral microvessels were assessedin vivo. BBB permeability was evaluated in LPS-treated mice, while barrier integrity was measured in primary human brain microvascular endothelial cells (BMVECs) using transendothelial electrical resistance (TEER). Cytokine release, adhesion molecule expression (VCAM-1 and ICAM-1), and inflammatory gene expression in isolated cerebral microvessels were also analyzed. Statistical significance was determined using comparative analyses between treatment and control groups.ResultsAmong the compounds tested, RO6839828 and HU-910 demonstrated the greatest efficacy in reducing leukocyte adhesion to and migration across the BBB. CB2receptor agonists significantly attenuated BBB hyperpermeability in LPS-treated mice and improved endothelial barrier integrityin vitro, as reflected by increased TEER values. Treatment also reduced cytokine release and decreased expression of VCAM-1 and ICAM-1. In addition, CB2agonists attenuated dysregulation of multiple inflammation- and endothelial injury-related genes in cerebral microvessels isolated from LPS-treated mice. Pre-treatment of either BMVECs or primary human monocytes reduced monocyte adhesion to and transmigration across endothelial monolayersin vitro.ConclusionsNovel orally bioavailable CB2receptor agonists reduced neuroinflammation-associated BBB dysfunction and leukocyte trafficking in bothin vitroandin vivomodels. These findings support the therapeutic potential of CB2receptor agonists for the treatment of neurological diseases associated with neuroinflammation and BBB disruption.

Endothelial glycocalyx damage underlies the generalized endothelial dysfunction in preeclampsia.

High-throughput RNA sequencing identifies hub genes and anti-inflammatory effects of β-caryophyllene in cerebral ischemia-reperfusion via p38MAPK/NF-κB modulation.

Aortic dissection (AD) is a vascular surgical disease that seriously threatens human health. Due to a high misdiagnosis rate and unclear pathogenesis, it brings greater challenges to AD patients and vascular surgeons. This study aimed to explore sensitive diagnostic markers and potential therapeutic targets of AD from the perspective of cellular senescence, which has been our long-term concern. We downloaded the expression matrix of AD and control samples from the Gene Expression Omnibus database and obtained the senescence-related gene set. Differentially expressed genes (DEGs) in AD and control groups were analyzed by the "limma" package. Gene Ontology, Disease Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were carried out to demonstrate the enrichment function of DEGs. Two sensitive screening diagnostic marker algorithms, the least absolute shrinkage and selection operator and support vector machine-recursive feature elimination, were used to identify target genes in combination with senescence-related genes. Receiver operating characteristic curves for targeted genes were plotted to assess diagnostic efficacy. Gene set enrichment analysis was performed to preliminarily explore the pathways enriched in the 2 groups. CIBERSORT was used to look for differentially infiltrating immune cells, and Spearman analysis was carried out to explore the association between targeted genes and infiltrating immune cells. A total of 111 DEGs were identified, which were closely related to regulation of leukocyte migration, cellular transition metal ion homeostasis, transition metal ion homeostasis, and detoxification of copper ion from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Disease Ontology analysis found that these DEGs were mainly involved in acute myocardial infarction, vasculitis, and coronary artery disease. Hexokinase-3 (HK3) was identified as an overlapping gene of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and senescence. HK3 showed good diagnostic efficacy (area under the receiver operating characteristic curve = 0.924 in the integrated cohort and 0.914 in the validation cohort). Correlation analysis results showed that HK3 was positively correlated with monocytes, neutrophils, and natural killer cells resting, while B cells naive, mast cells resting, and macrophages M1 were negatively correlated. HK3 was a potential biomarker for AD diagnosis and a target for precision therapy, and HK3 is also closely related to immune infiltration.

Polycyclic aromatic hydrocarbons (PAHs), ubiquitous environmental pollutants, are considered significant environmental factors contributing to the pathogenesis of RA. Benzo[a]pyrene (BaP), a key component of PAHs, may be associated with RA onset; however, the underlying toxicological mechanism remains to be fully elucidated. In this study, we systematically addressed this knowledge gap using an integrated approach combining network toxicology, machine learning, and molecular docking. Initially, a network toxicology analysis was conducted based on the molecular structure of BaP. By integrating and screening target information from multiple databases, 15 potential RA-related target genes of BaP were ultimately identified, and their interaction network was constructed. GO and KEGG enrichment analyses revealed that these genes were significantly enriched in biological processes such as leukocyte migration and immune cell signal transduction and were associated with the NF-κB and T cell receptor signaling pathways, among others. Subsequent topological analysis using the STRING database and Cytoscape software screened out five core genes (LCK, ZAP70, ITK, GZMA, and ITGAL), whose importance was further validated through machine learning. Molecular docking and molecular dynamics simulation results indicated that BaP exhibits strong binding affinity for the protein products of these target genes, resulting in the formation of conformationally stable complexes. In summary, this study employs an integrated computational approach to elucidate the potential mechanisms by which BaP may contribute to RA development, thereby offering a theoretical foundation for future investigations into the prevention and treatment of RA associated with environmental pollutants.

Background: Venous thromboembolism (VTE) is a thromboinflammatory disorder involving coordinated activation of coagulation, endothelial dysfunction, and inflammatory signaling. Low-molecular-weight heparins (LMWHs) may exert pharmacological effects beyond anticoagulation. This study compared enoxaparin, bemiparin, and tinzaparin and explored potential multi-target mechanisms using molecular docking, network pharmacology, and enrichment analyses. Methods: In this retrospective cohort study, patients with acute VTE treated with therapeutic-dose LMWHs were analyzed. Stabilized IPTW based on multinomial propensity scores was used to reduce baseline imbalance between treatment groups. Clinical recovery was assessed using the Clinical Severity Score (CSS). Thromboinflammatory biomarkers (MPV, hs-CRP, NLR, fibrinogen) were evaluated during follow-up. Molecular docking, STRING/Cytoscape-based protein–protein interaction, and enrichment analyses were performed. Results: Median time to symptom resolution was 31 days with enoxaparin, 28 days with bemiparin, and 24 days with tinzaparin (log-rank p < 0.001). Recovery was faster with bemiparin (HR 1.28, 95% CI 1.05–1.56) and tinzaparin (HR 1.72, 95% CI 1.41–2.10). Tinzaparin showed greater reductions in hs-CRP, MPV, NLR, and fibrinogen (all p < 0.05) and less analgesic use beyond 10 days (19.7% vs. 27.0% and 33.2%; p < 0.001). Docking analyses identified plausible conformations (root-mean-square deviation, RMSD ≤ 2 Å). Given the structural flexibility and heterogeneous chain length of LMWHs, rigid docking algorithms may not fully capture biologically relevant conformations. Therefore, docking results should be interpreted as qualitative interaction mapping rather than quantitative binding affinity estimation. Network analysis highlighted F3, TNF, IL6, and VWF, while enrichment analyses suggested involvement of cytokine signaling, leukocyte migration, and thromboinflammatory pathways. Conclusions: LMWH therapy was associated with improved thromboinflammatory markers and clinical recovery, with tinzaparin showing comparatively more favorable thromboinflammatory biomarker trajectories and recovery dynamics within the limitations of this observational analysis. Integrated clinical and in silico findings provide hypothesis-generating insights into potential multi-target pharmacological effects beyond anticoagulation; however, these observations should be interpreted cautiously and require experimental validation.

The formation of brain edema is one of the key factors that determine patient outcomes following traumatic brain injury (TBI). Despite decades of research, no causal treatment is available to date. Among the many factors discussed, inflammation is believed to facilitate brain edema formation. Following brain trauma, leukocytes become activated, interact with the vascular endothelium, and transmigrate into pericontusional tissue. It was hypothesized that this process may affect the permeability of the blood-brain barrier and facilitate vasogenic brain edema formation. Thus, our study aimed to investigate the role of leukocyte adherence and migration in brain edema formation after experimental TBI by inhibiting the integrin CD18. Male C57BL/6 mice (n = 7/group) underwent controlled cortical impact (CCI) and were randomly assigned to one of three groups: (1) sham operation, (2) CCI + control IgG, or (3) CCI + anti-CD18 antibody. Treatment was administered 30 min before and 24 h after CCI. The anti-inflammatory effect of the anti-CD18 treatment was verified using invivo two-photon microscopy and immunohistochemistry 48 h after CCI (n = 5/group). Lesion volume and brain edema formation were assessed by T2 and free-water diffusion magnetic resonance imaging longitudinally at 1, 2, 3, 5, and 7 days after the trauma or sham operation. Neurological function was determined daily using the Modified Neurological Severity Score. Vasogenic brain edema formation was detectable up to 7 days after trauma; no edema formation occurred in animals that underwent a sham operation. Anti-CD18 treatment reduced leukocyte-endothelium interaction and leukocyte migration into the brain after trauma to nearly control levels; however, it did not reduce lesion volume or brain edema formation. Preventing the adhesion of circulating leukocytes to cerebral vessels and their migration into the brain parenchyma does not reduce the formation of vasogenic brain edema and lesion volume after TBI in mice.

ABSTRACTThe liver's contribution to pulmonary arterial hypertension (PAH) pathogenesis remains unclear. We hypothesized that the liver promotes inflammatory injury to the pulmonary endothelium. PAH patients without liver disease with pulmonary artery endothelial cell (PAEC) biopsies were included. Unsupervised CART analysis of liver serologies identified subclinical dysfunction clusters; machine‐learning models informed differential expression and protein–protein interaction network assembly. PAEC transcriptomes were compared to liver and lung data from monocrotaline and Sugen‐Hypoxia rats. Liver fibrosis was assessed in rat and human PAH livers. Among 25 PAH patients (76% female, median age 61 [30–84] years), CART identified clusters distinguished by Model for End‐Stage Liver Disease Sodium (MELD‐Na) ≥ 12, which was associated with higher Fibrosis‐4 scores and higher pulmonary vascular resistance (ß = 0.5 Wood units per point increase in MELD‐Na, 95% CI 0.2–0.8, p = 0.005) after adjustment for right atrial pressure. Subjects with MELD‐Na ≥ 12 had decreased 6‐min walk distance (353 [120–576] m vs. 411 [300–600] m, p = 0.03). In comparing the two clusters, a protein–protein interaction network analysis identified IL‐6 as the primary hub of a transcriptional module enriched for leukocyte chemotaxis and myeloid leukocyte migration (all FDR < 0.05) among the High‐MELD‐Na group. Rat livers demonstrated immune activation and a trend toward increased fibrosis (20.8 vs. 16.6% area stained, p = 0.09), and human PAH livers without liver disease showed an intermediate fibrotic phenotype between controls and portopulmonary hypertension, though this did not reach statistical significance. Our observations support a lung–liver axis in PAH even in the absence of liver disease, warranting further study.

Cenostigma pluviosum var. peltophoroides, known as “sibipiruna,” is a plant rich in polyphenols used in traditional medicine for gastrointestinal disorders. The study aimed to investigate the chemical composition of the crude ethanolic extract of the stem bark (CEECP), evaluating its in vivo toxicity, genotoxicity, mutagenicity and anti-inflammatory activity. The plant material was macerated in 95% ethanol for 72 h, and the solvent was removed by rotary evaporation to obtain CEECP. Chemical characterization was performed by HPLC-ESI-MS/MS in negative mode. In vivo approaches were performed using male/female Swiss albino mice. Acute toxicity was assessed at a single high dose of 2000 mg/kg. Mutagenicity was investigated by the micronucleus test and genotoxicity by the comet assay, both at a dose of 2000 mg/kg. Anti-inflammatory activity was evaluated in carrageenan-induced paw edema and peritonitis models, at doses of 50, 100, and 200 mg/kg. HPLC-ESI-MS/MS analysis showed the presence of hydrolyzable tannins, phenolic acid heterosides, and biflavonoids. The safety profile of the CEECP was demonstrated for the first time, with no evidence of acute toxicity, mortality, mutagenicity, or genotoxicity at the tested doses. The extract significantly reduced paw edema in a dose-dependent manner at doses of 100 and 200 mg/kg, with inhibition rates of 65.78% and 73.12%, respectively, and also decreased leukocyte migration in the peritonitis model by 61.81% and 72.79% at the same doses. These findings indicate the CEECP as a source of pharmacologically relevant phytocompounds and, most notably, demonstrate its pronounced anti-inflammatory activity. Furthermore, the extract exhibited a favorable safety profile in the toxicological evaluations, highlighting the extract as a promising anti-inflammatory agent.

The luminal surface of blood vessels is covered by a hydrated mesh of sugars and proteins termed the endothelial glycocalyx. The glycocalyx forms a permeability barrier and helps regulate leucocyte migration. Directly detecting glycocalyx damage could provide a major advance in vascular health monitoring. Here we show that red blood cell glycocalyx mirrors the endothelial glycocalyx in health and disease. Using peripherally sampled blood, we confirm that red blood cell glycocalyx measurements predict cardiac and renal endothelial glycocalyx alterations and direct measures of endothelial barrier function in male rats. To investigate the underlying mechanism, we use Azide-Alkyne cycloaddition (‘Click’ chemistry) to confirm that contact between endothelial and red blood cells results in continual reciprocal transfer of glycocalyx components. These discoveries facilitate real-time monitoring of endothelial damage in patients whilst simultaneously providing a potential explanation as to how red blood cells maintain their glycocalyx during circulation.