Search Results (28,435)

Background: Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging concern worldwide. Current chemotherapies show limited efficacy during chronic infection, and no licensed vaccine is currently available. We previously developed the chimeric antigen N-Tc52/TSKb20 as a vaccine candidate against T. cruzi infection. In a murine model, this vaccine induced robust antigen-specific immune response associated with protection shortly after vaccination. Objectives: Here, we investigated the long-term persistence and effector functions of the immune responses elicited by this vaccine candidate. Methods: Both female and male C57BL/6 mice were immunized with three doses of N-Tc52/TSKb20 formulated with QuilA adjuvant. Serum samples collected 170 days post-immunization were analyzed for antigen-specific antibodies by ELISA and for trypanolytic activity against cell-derived trypomastigotes using an in vitro functional assay. Cellular immune responses were evaluated by measuring cytokine production, T cell activation, and memory T cell responses following in vitro re-stimulation with the vaccine antigen or T. cruzi antigens. Results: N-Tc52/TSKb20 vaccination induced a sustained antigen-specific humoral response, characterized by long-lasting IgG2c antibodies and functional activity persisting for up to 170 days post-immunization. In parallel, vaccination promoted long-term activation of antigen-specific CD8⁺ T cells and production of TNF-α and IFN-γ upon antigen re-encounter. A sex-dependent tendency was observed for IL-10, with increased production in vaccinated female mice. Moreover, vaccinated animals exhibited increased frequencies of central and effector memory CD4⁺ and CD8⁺ T cells in response to T. cruzi antigens, with a predominant contribution of CD8⁺ T cells, indicating the establishment of parasite-specific T cell memory. Conclusions: Together, these findings demonstrate that vaccination with N-Tc52/TSKb20 induces a long-lasting Th1-biased immune response characterized by trypanolytic antibodies, functional and durable T cell responses, and parasite-specific memory T cells. This immunological profile supports the potential of N-Tc52/TSKb20 as a promising vaccine candidate for Chagas disease and highlights its capacity to elicit immune mechanisms that have been associated with protection against T. cruzi infection. Full article

Multiple sclerosis (MS) is a heterogeneous autoimmune disorder of the central nervous system of polygenic nature. Uncovering the genetic predictors of MS phenotype can help to explain the nature of the disease’s clinical heterogeneity, and contribute to the development of novel tools for precise disease prognosis. We conducted a retrospective genetic association study of 35 polymorphic variants in immune-related genes with MS severity assessed using the Multiple Sclerosis Severity Score (MSSS) in a sample of 548 Russian relapsing-onset MS patients who have not previously received immunomodulatory therapy. Variants in the CXCR5, EOMES, TNFRSF1A, IRF8, PVT1, CCR5, HLA-DRB1, IL6, TCF7, and CD40 genes were identified as MSSS-associated in at least two of the three models analyzed (MSSS > 3.5 versus ≤3.5; MSSS > 5.0 versus <2.5; MSSS as a continuous variable). Among them, variants in CCR5, HLA-DRB1 and IL6 genes were associated with MSSS only in women, while variants in the TCF7 and CD40 genes only in men. The variant in CXCR5 was MSSS-associated both in the total sample and in subgroups of female and male MS patients. Thus, we demonstrate that several GWAS-identified MS risk genes, along with other immunological loci, act as modifiers of the MS phenotype. Full article

Phycobiliproteins (PBPs) are a family of pigment-proteins renowned for their exceptional light-harvesting, fluorescent, and antioxidant properties. Among cyanobacteria, Spirulina stands out as one of the richest natural sources of PBPs, particularly phycocyanin (PC) and allophycocyanin (APC), yet the large-scale production of analytical-grade PBPs remains hampered by an inherently complex downstream process that relies on multiple purification steps, compromising both yield and scalability. This work presents a streamlined strategy to obtain analytical-grade PC, combining ultrasound-assisted extraction (UAE) with an aqueous ionic liquid (IL) solution and a single hydrophobic interaction chromatography (HIC) step, integrated within a biorefinery framework. The proposed approach yielded analytical-grade PC with a recovery of up to 50.44% and enhanced APC purity up to 10.57-fold. Furthermore, the IL was successfully reused in both extraction and purification steps without compromising yield or purity. The environmental performance of the proposed process was assessed through a cradle-to-gate life cycle assessment (LCA), with system boundaries encompassing the following biorefinery stages: cultivation, harvesting and drying, PC extraction and purification, post-processing, and spent biomass valorization via anaerobic digestion. The LCA identified the main environmental hotspots and guided the proposal of targeted process improvements—particularly HIC salt substitution and increased IL recovery—which reduced environmental impacts by 65.9–89.8% across most categories. The proposed strategy was further benchmarked against two model scenarios for analytical-grade PC production, one conventional and one innovative, revealing its relative advantages and limitations. Overall, this work demonstrates a viable pathway for producing high-purity PC that balances process efficiency with environmental sustainability, supporting the development of greener microalgae-based bioprocesses. Full article

Shuanghuanglian oral liquid (SHL) is widely used in companion animals and poultry, but its molecular mechanism in pneumonia–myocarditis comorbidity and heart–lung inflammatory crosstalk remains largely unclear. This computational study investigated the conserved AKT1/HIF1A-mediated immunoregulatory mechanism of SHL and its cross-species translational potential in veterinary medicine. Network pharmacology was integrated with GO, KEGG, and Reactome enrichment analyses, protein–protein interaction network construction, ADMET evaluation, cross-species sequence homology analysis (human, dog, cattle, and pig), molecular docking, and molecular dynamics simulation. A total of 61 active compounds, 251 putative targets, and 52 common targets associated with pneumonia and myocarditis were identified. These targets were mainly enriched in inflammation- and immune-related pathways, including TNF, IL-17, AGE–RAGE, and PPAR signaling. AKT1 and HIF1A showed high sequence conservation across species (85–98%). Key compounds exhibited favorable binding affinity to AKT1, and molecular dynamics simulation suggested the stability of the Baicalein–AKT1 complex. ADMET analysis suggested favorable pharmacokinetic properties and low predicted toxicity. These findings suggest that SHL may potentially alleviate pneumonia and myocarditis through modulation of the conserved AKT1/HIF1A axis and support its potential as a complementary therapeutic approach for managing heart–lung inflammatory diseases in multiple livestock species. This entirely computational study highlights promising mechanisms that should be further validated in vivo. Full article

Background/Objectives: Bursera bipinnata (DC.) Engl. resin (locally known as “copal blanco”) is traditionally used in Mexican ethnomedicine to treat infected wounds and skin inflammation, but the bioactive constituents underlying these effects remain largely uncharacterized. This study aimed to identify the compounds responsible for the wound-healing properties of the resin through bioactivity-guided fractionation and to evaluate their anti-inflammatory and antibacterial activities as complementary mechanisms supporting tissue repair. Methods: Crude resin (1.2–5.0 mg/mL) was assayed for anti-inflammatory activity in the TPA-induced ear-edema model in BALB/c mice, for antibacterial activity (MIC) against six clinically relevant strains, and for wound-healing activity in a murine excisional model with pirfenidone (PFD) as the reference drug (n = 5 per group). Bioactivity-guided fractionation followed by spectroscopic elucidation (¹H- and ¹³C-NMR, IR, EI-MS) led to the isolation of five constituents. Stigmasterol, the most active compound, was subsequently evaluated in an LPS-induced systemic inflammation model (oral administration, 20 mg/kg/day × 3 days) to characterize its immunomodulatory profile (TNF-α, IL-1β, IL-6, IFN-γ, IL-10) and in the wound-healing model to quantify local IL-6, IL-10 and TGF-β1 in skin homogenates. Results: The crude resin (5.0 mg/mL) achieved 99.63% wound closure at day 12 and a 49.08% reduction in TPA-induced ear edema, comparable to indomethacin (55.76%). The resin displayed selective antibacterial activity against Streptococcus pyogenes (MIC 125 µg/mL) and Salmonella typhimurium (MIC 250 µg/mL). Bioactivity-guided fractionation yielded the phytosterol stigmasterol (1), three lupane-type triterpenoids (lupeol acetate (2), lupenone (3), 3-epilupeol (5)), and the sesquiterpenoid caryophyllene oxide (4). At an equimolar 1 µM concentration, stigmasterol (1) shortened the mean wound-healing time to 10.3 ± 0.4 days, comparable to pirfenidone, and was associated with attenuation of systemic TNF-α, IL-1β and IL-6 peaks and with sustained local IL-10 and TGF-β1 expression. Histological assessment confirmed accelerated re-epithelialization and improved collagen organization. The resin was non-irritant in the OECD 404 acute dermal test (Primary Irritation Index = 0.00). Conclusions: These findings provide pharmacological evidence supporting the traditional use of B. bipinnata resin for wound healing. Stigmasterol (1), together with the lupane-type triterpenoids lupenone (3) and 3-epilupeol (5), were identified as key bioactive constituents. The data are consistent with a coordinated immunomodulation, in which stigmasterol is associated with reduced systemic pro-inflammatory signalling and increased local IL-10/TGF-β1 expression, an interpretation that should be confirmed in chronic and impaired wound-healing models. Full article

Background/Objectives: The goal of this study was to show the consistency between the inflammatory and anti-inflammatory response in the early postoperative period after corneal refractive surgery (LASIK and PRK), represented by the levels of specific cytokines in the tear film. Materials/Methods: A total of 68 myopic eyes (31 in the LASIK and 37 in the PRK group) had 3 samples of tear film taken, one before surgery (t₀), another 1 h after surgery (t₁) and the third 24 h after surgery (t₂). The tear samples were then analyzed by flow cytometry in order to determine the levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IFN-γ, TNF-α) and the levels of anti-inflammatory cytokines (IL-4, IL-10). Results: A statistically significant positive correlation was found between the concentrations of all pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IFN-γ, TNF-α) and all anti-inflammatory cytokines (IL-4, IL-10), respectively, for both t₁ and t₂ in the group of eyes that underwent LASIK. In the PRK group, there was a statistically significant positive correlation for all cytokines (pro-inflammatory and anti-inflammatory) at t₁; however at t_2, there was no correlation between IL-1β and IL-10, IL-6 and IL-10, IL-8 and IL-10, and IFN-γ and IL-10. In contrast, for other correlations between pro-inflammatory and anti-inflammatory cytokines in the same observation time (t₂), a positive correlation was observed. Conclusions: There is a consistency between the inflammatory and anti-inflammatory responses in the early postoperative period after refractive surgery, which persists longer after LASIK compared to PRK. This difference may explain the different clinical courses in patients after undergoing these procedures. Full article

Background: Macrophage pyroptosis contributes substantially to sepsis-induced lung injury, yet effective therapeutic strategies remain limited. This study aimed to determine the protective effects of meloxicam, a non-steroidal anti-inflammatory drug, and the underlying mechanisms in this context. Methods:In vivo, CLP mice were treated with meloxicam (20 mg/kg). In vitro, LPS-primed macrophages were stimulated with ATP or nigericin in the presence or absence of meloxicam. Levels of pyroptosis-associated proteins (cleaved Caspase-1, mature IL-1β, GSDMD-NT), NLRP3 inflammasome assembly, and the CBP/TXNIP/p38 signaling axis were assessed by Western blot. Mitochondrial membrane potential (ΔΨm) and intracellular ROS were measured. Overexpression of COX-2, TXNIP, and CBP was also performed. Results: Meloxicam significantly improved survival, reduced lung injury, and suppressed pyroptosis-associated proteins in CLP mice. In vitro, meloxicam dose-dependently enhanced macrophage viability and reduced LDH, IL-1β, and IL-18 release. The protective effects of meloxicam were mediated by inhibition of NLRP3 inflammasome priming and assembly, disruption of NLRP3-ASC-pro-Caspase-1 complex formation, and suppression of ASC oligomerization. Meloxicam also inhibited the CBP/TXNIP/p38 axis, an effect reversed by TXNIP or CBP overexpression. Furthermore, meloxicam restored ΔΨm and reduced ROS accumulation; these effects were abrogated by the ROS inducer imiquimod. Importantly, the anti-pyroptotic effects of meloxicam were independent of COX-2 inhibition. Conclusions: These findings expand the pharmacological profile of meloxicam and support its repurposing as a therapeutic agent for sepsis-associated lung injury. Full article

Probiotics are widely studied as antibiotic alternatives in commercial aquaculture, yet their effects on fish maintained under long-term aquarium conditions remain poorly understood. This study addressed this gap by evaluating dietary Escherichia coli Nissle 1917 (EcN) supplementation on gut microbiota and inflammatory cytokine expression in hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) from a recirculating aquarium system. In this study, hybrid grouper were maintained in triplicate tanks under long-term aquarium environments, and fed a basal diet with 1 × 10⁸ CFU/g EcN (SS group) or a control diet (CS group) for 28 consecutive days. Based on 16S rRNA high-throughput sequencing and qPCR, the intestinal microbiota and expression levels of IL-4, TNF-α, and IL-1β were measured. At the phylum level, the relative abundance of Firmicutes increased from 15.63% (CS) to 66.70% (SS), while Proteobacteria decreased from 76.77% to 30.61%. At the genus level, Exiguobacterium became the dominant taxon in the SS group. Furthermore, EcN supplementation significantly upregulated IL-4 expression and downregulated TNF-α and IL-1β expression. EcN supplementation significantly altered gut microbiota composition, with marked changes in community structure and notable shifts in dominant taxa. Thus, this study provides one of the investigations into EcN-mediated restructuring of intestinal bacterial communities and modulation of host immune transcriptional responses in hybrid grouper maintained under controlled aquarium settings. These findings offer a foundation for designing microbiome-targeted interventions in captive marine fish systems. Full article

Fruit tree leaves are an abundant agro-waste material with promising yet underexplored biological potential. This study compared the biological activity of aqueous extracts obtained from apple (Malus domestica), apricot (Prunus armeniaca), and cherry (Prunus cerasus) leaves and their kombucha-fermented counterparts in the context of cosmetic and dermatological applications. Phytochemical composition before and after fermentation was analyzed chromatographically. Antioxidant activity was evaluated using DPPH, ABTS, and FRAP assays, while intracellular reactive oxygen species (ROS) levels in keratinocytes and fibroblasts were assessed using the H₂DCFDA probe. Cytotoxicity was determined by Alamar Blue and Neutral Red assays. Antimicrobial activity against seven bacterial strains was investigated using minimum inhibitory concentration and disc diffusion methods. Anti-inflammatory activity was evaluated in LPS-stimulated THP-1 cells by measuring TNF-α, IL-1β, and IL-6 levels using ELISA. The influence of the samples on collagenase, elastase, and hyaluronidase activity was also analyzed. Fermentation increased the content of selected phenolic compounds and enhanced antioxidant, antimicrobial, anti-inflammatory, and anti-ageing properties. Ferments more effectively reduced oxidative stress in skin cells and showed no cytotoxicity within the tested concentration range. These findings indicate that kombucha fermentation may support the valorization of fruit tree leaf agro-waste as multifunctional ingredients for skincare formulations. Full article

Background/Objectives: This study aimed to verify a prediction model identifying the relationships and pathways among factors associated with Korean nursing students’ provision of person-centered care to patients with dementia. Methods: This was a covariance structure analysis study to establish a hypothetical model of 313 Korean nursing students located in a metropolitan area. IBM SPSS version 18.0 (Chicago, IL, USA) and AMOS version 5.0 (Chicago, IL, USA) were used to analyze the data. Structural equation modeling analysis was applied to verify convergent and discriminant validity using higher-order factor analysis in the final model analysis. Results: The model fit indices of the research model were as follows: χ²/df = 1.83 (p < 0.001), GFI = 0.91, AGFI = 0.88, NFI = 0.91, CFI = 0.90, RMR = 0.04, and RMSEA = 0.05. The factors affecting person-centered care, nursing professionalism (γ = 0.45, p = 0.024), and empathy (γ = 0.21, p = 0.036) showed significant associations, whereas clinical practice adaptation (γ = 0.21, p = 0.013) and nursing professionalism (γ = 0.08, p = 0.004) had indirect effects. These factors explained 40% of the variance in person-centered care. Conclusions: This study is significant because it provides basic data for developing an educational program that can improve the person-centered care capacity of domestic nursing students by confirming that clinical practice adaptation, nursing professionalism, and empathy are important factors related to person-centered care. Full article

Background: The incidence of inflammatory bowel disease (IBD) is growing in the population. At present, the etiology of inflammatory bowel disease remains unclear, and there is no effective and low-toxic therapeutic drug. This study aimed to investigate the role of Lobenzarit (Lbz) in the treatment of colitis in mice as well as the underlying mechanism. Methods: In this experiment, colitis was induced in mice with dextran sulphate sodium (Dss). Subsequently, the role of Lbz in colitis and its underlying mechanisms were examined using H&E staining, TEM, ELISA, PCR, and other assays. Results: Lbz significantly attenuated the related symptoms of Dss-induced colitis in mice. In addition, Lbz suppressed neutrophil infiltration and restored macrophage polarization towards an anti-inflammatory state. Lbz also inhibited (p < 0.05) the activation of signaling pathways TLR4 and MAPK (51.61% decrease for TLR4 and 56.94% decrease for MAPK), reduced the release of inflammatory factors as it significantly decreased (p < 0.05) colonic IL-1β, TNF-α, IFN-γ, COX2, and VEGF (47.63, 42.49, 53.42, 58.74, and 61.28% decreases respectively) thereby attenuating the inflammatory response in mice. Lbz administration also restored the permeability of the intestinal barrier by increasing (p < 0.05) tight junction-associated proteins (claudin-1, occludin, and ZO-1 with a 5.36- and 2.26-fold increase for claudin-1 and ZO-1, respectively) and decreasing (p < 0.05) MALK levels by 53.51%. In addition, Lbz upregulated colonic Cytochrome C oxidase II, PDH, and ATP synthase levels and upregulated CD163, CD206, c-Maf, and PPAR-γ levels as compared to the DSS-treated group. Conclusions: Lbz has a repairing effect on Dss-induced colitis and may alleviate Dss-induced colitis by targeting the TLR4 pathway and promoting intestinal stem cell proliferation. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrent intestinal inflammation and mucosal injury. This study evaluated the protective potential of red ginseng ethanolic extract (RGEE) using a dextran sulfate sodium (DSS)-induced colitis mouse model and an LPS-stimulated RAW 264.7 macrophage model. Preliminary LC-MS profiling was also performed to characterize the detectable chemical features of RGEE. In vivo, RGEE alleviated DSS-induced body weight loss, disease activity, colon shortening, spleen enlargement, and histopathological injury, with the histopathological score reduced by approximately 51.1%. RGEE also partially improved DSS-induced hematological alterations without causing obvious changes in major organ weights. In vitro, RGEE showed no obvious cytotoxicity up to 250 μg/mL and reduced LPS-induced NO, TNF-α, IL-6, and IL-1β production by approximately 60.0–67.1%. LC-MS analysis putatively annotated several saponin-related features, including notoginsenoside R1 and ginsenosides Rb1, Rb2, Rh1, Rh4, and Rh2. These findings suggest that RGEE has protective potential against DSS-induced colitis, which is associated with the suppression of inflammatory mediator production. Further studies are needed to clarify its active constituents and mechanisms of action. Full article

Background: Acute myocardial infarction (AMI) remains the most lethal critical emergency worldwide. Although Angong Niuhuang Pill (ANP) is an established rescue medicine that has demonstrated outstanding therapeutic potential for cardiovascular diseases, its modern molecular mechanism has never been systematically elucidated because of its chemical complexity and unidentified targets. Methods: This study utilizes a multi-layer analytical pipeline of AI mining, network pharmacology, transcriptomics, and experimental confirmation. The components of ANP were comprehensively identified by UHPLC-Q Exactive Orbitrap HRMS. The TranSiGen algorithm was utilized to deeply mine the data and rank the components according to their relevance to AMI. The top 20 components were selected as prior weights and introduced into network pharmacology for analysis. Subsequently, a mouse model of AMI was established by ligating the left coronary artery. Cardiac function in the mice was evaluated by echocardiography and serum biochemical indicators. The pathological changes in the heart tissue were assessed by hematoxylin-eosin (H&E) and Masson staining. Cardiac transcriptome sequencing was performed, and pathway enrichment was analyzed by KEGG. The key pathways were verified by qPCR and immunofluorescence, achieving cross-validation between AI prediction and experimental findings. Results: The identification of ANP resulted in the detection of a total of 73 compounds, and the TranSiGen algorithm was employed to prioritize these compounds, yielding a ranked list of the top 20 candidates. Functional evaluation using echocardiography, serum biochemical markers, and histopathological examination demonstrated that ANP significantly ameliorated cardiac function in mice following myocardial infarction. Integration of network pharmacology and transcriptomic enrichment identified convergent axes of IL-17 signaling and mitochondrial quality control, which were subsequently experimentally validated as mechanisms by which ANP ameliorated cardiac injury. Experimental validation confirmed that ANP downregulated protein expression of IL-17A and TNF-α, normalized PINK1 and LC3-II/LC3-I marker profiles, with concomitant p62 reduction, thereby providing comprehensive molecular evidence at both transcriptional and translational levels to support the AI-driven predictions. Conclusions: This study identified IL-17 signaling and mitochondrial quality control as pathway axes associated with ANP-mediated cardioprotection against AMI, supported by AI-driven compound screening, transcriptome-network cross-validation, and experimental confirmation. This analytical framework may be adaptable to other complex TCM formulas for mechanism exploration and clinical translation. Full article

Background: Vitamin D, through its role in antimicrobial peptide (AMP) expression, may influence innate immunity and inflammation in urinary tract infections (UTIs). This study evaluated its role in patients with vesicoureteral reflux (VUR) and its contribution to the pathophysiology of reflux nephropathy (RN). Methods: We conducted a cross-sectional observational study of 25 pediatric patients with VUR, representing a subgroup analysis of a larger cohort examined in a previous study. We determined patients’ vitamin D status, correlated it with recurrent UTIs and RS, and explored its relationship with urinary LL-37, NGAL, and IL-6 levels as markers of innate immune function. Results: Serum vitamin D levels ranged from 10.7 to 123.2 ng/mL (mean 39.5 ng/mL); 12% had deficiency and 20% had insufficient levels. Low vitamin D levels were detected in patients with more than five acute pyelonephritis (APNs), with a mean value classified as insufficient (27.3 ng/mL). Patients with RS had a lower mean vitamin D level compared to those without (30.51 ng/mL vs. 41.23 ng/mL), though the difference was not statistically significant (p = 0.39). No significant associations were found between vitamin D and urinary IL-6 or NGAL levels. A strong positive correlation was observed between vitamin D and urinary LL-37/creatinine (r = 0.78, r² = 0.61). Conclusions: Vitamin D appears to influence the frequency of UTIs and the development of RS, primarily by modulating LL-37 secretion, suggesting a possible role in the pathophysiology of RN. Full article

Background/Objectives: Acute respiratory failure (ARF) encompasses heterogeneous etiologies, and early bedside prognostication remains challenging. Cytokines and chemokines may capture underlying biological severity and identify high-risk patients. We evaluated whether admission cytokine/chemokine profiles add incremental prognostic value over clinical risk factors in unselected ARF patients. Methods: This prospective, single-center cohort study enrolled adult patients admitted to medical ICUs with ARF requiring high-intensity respiratory support. Plasma samples were collected within 24 h of ARF diagnosis, and 19 cytokines/chemokines were measured using multiplex immunoassays. The primary outcome was ICU mortality. Univariate and multivariable logistic regression models assessed associations between biomarkers and mortality, with discrimination evaluated by the area under the receiver operating characteristic curve (AUC). Results: Among 41 patients, 15 (37%) died in the ICU. Non-survivors had higher rates of immunosuppression (80% vs. 38%, p = 0.010) and hematologic malignancy (67% vs. 31%, p = 0.026). CXCL10 (IP-10), IL-18, and CCL2 (MCP-1) were significantly higher in non-survivors, and IL-1Ra showed a marked numerical increase with a significant univariable association with ICU mortality, despite comparable severity scores and oxygenation indices at admission. A clinical core model (SOFA, immunosuppression, hematologic malignancy) achieved an AUC of 0.74 (95% CI 0.58–0.90); adding cytokines improved discrimination modestly (AUC 0.76–0.80). In highest-quartile survival analyses, IL-1Ra (p = 0.002), CXCL10 (p = 0.005), and CCL2 (p = 0.009) demonstrated significant survival separation. Conclusions: At ICU admission, CXCL10 (IP-10), IL-18, CCL2 (MCP-1), and IL-1Ra showed exploratory associations with ICU mortality and were prioritized as candidate inflammatory biomarkers. These findings require validation in larger multicenter cohorts. Full article