Search Results (3,491)

Neuroinflammation is a hallmark of multiple sclerosis (MS). MS is marked by glial cell activation, autoreactive T cells, and the release of pro-inflammatory cytokines and free radicals. Current therapeutic strategies aim to modulate the immune response using disease-modifying therapies, to slow disease progression. The specific aims of this study were: (a) to investigate the effect of cannabinoid acids on the release of glial neuroinflammatory mediators, (b) to examine the effect of intraperitoneally administered cannabinoid acids on symptoms of MS, and (c) to evaluate their effects on microglial and astrocyte activation and CD4⁺ T cell infiltration into the spinal cords of MS mice. Exposure of BV2 microglia to cannabinoid acids attenuated lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase by 40–90% it also reduced the release of nitric oxide and interleukin-17A. Among the cannabinoid acids tested, cannabidiolic acid (CBDA) significantly increased tumor necrosis factor alpha (TNFα) secretion by up to 40% in LPS-stimulated BV2 cells. Intraperitoneal administration of CBDA also resulted in a twofold increase in TNFα secretion in splenocytes isolated from MS mice, compared to untreated MS controls. This study provides evidence that CBDA significantly reduces neurological scores, while both cannabinoid acids attenuate microgliosis, astrogliosis, and CD4+ T cell migration in lumbar spinal cord sections of MS mice. These compounds cross the blood–brain barrier (BBB) and act directly within the central nervous system. The consistent elevation of TNFα in the presence of CBDA across three experimental models suggests a distinctive immunomodulatory role for CBDA, with potential therapeutic implications in MS. Full article

Background: Mycoplasma pneumoniae (MP) is a major cause of respiratory tract infections in children and adolescents. Currently, there is no licensed vaccine, underscoring the urgent need for the development of safe and effective vaccines. Objective: The aim of this study is to develop a recombinant subunit vaccine candidate incorporating three antigens: the P1 protein, the P40/90 complex, and a detoxified mutant of community-acquired respiratory distress syndrome toxin. The protective efficacy of this vaccine candidate was also evaluated. Methods: Target genes were codon-optimized for expression in E. coli, and the recombinant proteins were successfully expressed and purified. The low-toxicity CARDS toxin mutant was screened based on TNF-α secretion levels in stimulated RAW264.7 cells. A three-component vaccine composed of P1, P40/90, and the mutant CARDS toxin was formulated and adjuvanted with either Al(OH)₃ alone or in combination with CpG. Mice were immunized, and immunogenicity was assessed by measuring antigen-specific IgG antibody titers. Protective efficacy was evaluated following challenge by analyzing lung histopathology, bacterial load, and inflammatory cytokine levels. Results: Seven high-purity recombinant proteins were successfully produced, including P1, the P40/90 complex, wild-type CARDS toxin, and four CARDS toxin mutants (E132A, E132Q, H36A, R10A). The E132A mutant was selected due to its significantly reduced toxicity while retaining immunogenicity. The three-component vaccine effectively elicited antibody responses against each of the included antigens. After three immunizations, IgG antibody titers in all groups reached approximately 10⁴. Immunized mice showed markedly reduced pulmonary pathology scores (control group: 2 or 2.67; immunized groups: 1.67, 1.33, and 0) and significantly decreased bacterial loads in lung tissue (control: 30.11 ± 10.40 cp/μL; immunized groups: 20.72 ± 4.37 cp/μL and 8.51 ± 8.32 cp/μL). Furthermore, the group receiving the alum + CpG adjuvant exhibited approximately a 10-fold higher antibody response compared with the alum-only group, indicating enhanced protective efficacy. Conclusion: The three-component candidate vaccine, MPtriV, adjuvanted with Al(OH)₃ + CpG, demonstrates promising immunogenicity, safety, and protective efficacy against Mycoplasma pneumoniae infection, providing a viable strategy and experimental foundation for the development of MP subunit vaccines. Full article

Open-heart surgery with cardiopulmonary bypass (CPB) is a high-risk procedure with significant morbidity and mortality. CPB, tissue injury, blood loss, endotoxemia and ischemia–reperfusion injury induce a pronounced systemic inflammatory response, leading to endothelial glycocalyx (EG) damage and vascular endothelial dysfunction. Consequently, immune cells, reactive oxygen species, and enzymes gain free access to vascular endothelial cells, resulting in their dysfunction and enhancing inflammation, vascular permeability, and microvascular impairment. EG degradation is most commonly assessed by measuring the circulating levels of its degradation products. Additionally, CPB triggers an early inflammatory response that is characterized by the secretion of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, and IL-18, which play roles in initiating the process of EG injury. EG damage is further propagated by the sustained release of cytokines, inhibiting the regeneration of the glycocalyx layer. Heparanase and matrix metalloproteinases are enzymatic pathways involved in cytokine-mediated EG degradation after cardiac surgery, and the balance between the pro- and anti-inflammatory cytokines determines the magnitude and duration of the inflammatory response and EG impairment, which correlates with adverse clinical outcomes, including myocardial dysfunction, acute lung and kidney injury, neurological complications, and prolonged need for intensive care. Thus, identifying patients with an exaggerated cytokine response could potentially provide more personalized therapy based on the circulating biomarkers of EG shedding, and cytokine-directed preservation of EG represents a promising therapeutic strategy in vascular dysfunction prevention during and after open-heart surgery. In this review, we summarize the current knowledge on cytokine-mediated EG impairment following open-heart surgery with CPB. Full article

The increasing prevalence of multidrug-resistant (MDR) pathogens, particularly avian pathogenic Escherichia coli (APEC) and methicillin-resistant Staphylococcus aureus (MRSA), poses a severe threat to the breeding industry and human health. To develop novel antibiotic alternatives, we adopted a “converting virulence into therapy” strategy by leveraging the type VI secretion system (T6SS) of the APEC strain ACN17-20. Guided by the structural analysis of T6SS Protein 00145, we rationally designed a series of amphipathic α-helical polypeptides. Among them, polypeptide A7 emerged as a lead candidate, exhibiting potent broad-spectrum antibacterial activity with negligible cytotoxicity against mammalian cells. Mechanistic studies revealed that A7 exerts a rapid bactericidal effect through a dual mode of action: physical disruption of bacterial membrane integrity leading to cytoplasmic leakage, and induction of lethal oxidative stress via reactive oxygen species (ROS) accumulation. Furthermore, A7 demonstrated excellent efficacy in eradicating pre-formed bacterial biofilms, addressing the challenge of persistent infections in breeding environments. In a mouse sepsis model induced by APEC and MRSA, A7 treatment significantly improved survival rates (60–80%), reduced bacterial loads in vital organs, and attenuated the systemic cytokine storm (TNF-α and IL-1β), thereby alleviating immune-mediated tissue damage. In conclusion, this study identifies polypeptide A7 as a safe therapeutic agent with a dual mechanism of action, providing a promising strategy to combat MDR infections and reduce antibiotic dependence. Full article

Geopropolis, a complex natural product composed of propolis, wax, plant resins, and soil produced by Meliponine (stingless) bees, has traditionally been used for its therapeutic properties. Its chemically diverse composition and broad biological activities have recently attracted growing scientific interest. In this study, we characterized the physicochemical and immunomodulatory properties of a hydroalcoholic extract of geopropolis (HEG) from Melipona quadrifasciata (Mandaçaia). Physicochemical characteristics were determined by measuring moisture, ash, and wax content, and its bioactive constituents were identified by GC–MS. THP-1-derived macrophages were exposed to increasing HEG concentrations to assess cytotoxicity, and two sublethal doses were selected for immunomodulatory assays with or without LPS stimulation. Cytokine and chemokine secretion were quantified by CBA, and the expression of key immunoregulatory and angiogenic genes was evaluated by RT-qPCR. Chemical profiling revealed a high wax content and a predominance of di- and triterpenoids, largely derived from coniferous sources. In mccrophages stimulated with LPS, HEG at 31.25 and 62.50 µg/mL significantly reduced the secretion of pro-inflammatory mediators (IL-6, CCL2, CCL5, CXCL9, and CXCL10) while preserving cell viability. In unstimulated macrophages, HEG upregulated the expression of genes VEGFA and TGFB1 as well as the protein CXCL8, all of them associated with angiogenesis and tissue repair. These findings demonstrate that M. quadrifasciata geopropolis extract modulates macrophage activity, promoting a shift toward a reparative phenotype that integrates inflammatory resolution with pro-healing effects. These results underscore its pharmacological potential as a terpenoid-rich natural product with complementary anti-inflammatory and regenerative activities. Full article

Leucine-rich-repeat kinase 2 (LRRK2) is a multidomain protein highly expressed in immune cells and implicated in the regulation of immune functions including immune signaling, cytokine release and autophagy. LRRK2 is one of the therapeutic targets in Parkinson’s Disease (PD). Aberrant activation of LRRK2 can also contribute to intestinal inflammation, mainly in inflammatory bowel disease (IBD). Hence the modulation of LRRK2 may influence gut inflammation providing an improvement in disease outcomes. Over the years, microRNAs (miRNAs) have acquired much attention thanks to their potential as therapeutic targets in several pathological conditions, including inflammatory disorders. In this study, we aimed to examine the ability of miR-369-3p in the modulation of autophagy targeting LRRK2 expression. Bioinformatics analysis revealed that Lrrk2 is a target gene of miR-369-3p, and LRRK2 expression was increased in ulcerative colitis patients compared with that in a healthy control. In in vitro analysis, we validated that mimic transfection with miR-369-3p in Raw264.7 significantly reduced the expression of LRRK2 both in basal and inflammatory conditions. Moreover, the inhibition of LRRK2 limited the nuclear translocation of Nuclear factor kappa B (NF-κB) induced by lipopolysaccharide (LPS) stimulation. In turn, we found that, in inflammatory conditions, the intracellular increase in miR-369-3p precluded the inhibition of autophagy by LRRK2 by restoring autophagy marker light chain 3 (LC3)II/I ratio, BECLIN-1 and decreasing p62 expression. Furthermore, we detected that the upregulation of miR-369-3p decreased the release of pro-inflammatory mediators Tumor necrosis factor (TNF), C-C motif ligand 2/Monocyte chemoattractant protein-1 (CCL2/MCP-1), C-C motif ligand 3/Macrophage inflammatory protein-1 alpha (CCL3/MIP-1α) and C-C motif ligand 5/Regulated on activation, normal T-cell expressed and secreted (CCL5/RANTES) and increased the anti-inflammatory cytokine interleukin 10 (IL-10) in response to LPS. This study supports the anti-inflammatory potential of miR-369-3p in immune cells and suggests the potential of miR-369-3p as a therapeutic agent in the treatment of acute intestinal inflammatory conditions such as ulcerative colitis. Full article

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease with a high fatality rate, and no licensed vaccines are currently available. The nucleoprotein (NP) of the Crimean-Congo hemorrhagic fever virus (CCHFV) plays a critical role in viral replication and immune recognition, making it a promising target for vaccine development. This study aimed to design and evaluate a multiepitope recombinant DNA vaccine targeting the NP of CCHFV. Methods: Cytotoxic T lymphocyte (CTL) epitopes from the NP were predicted via immunoinformatics approaches and systematically assessed for antigenicity, allergenicity, toxicity, hydrophobicity, and global population coverage. The selected epitopes were incorporated into four DNA vaccine constructs driven by a cytomegalovirus promoter, adjuvanted with human β-defensin 3 (hBD3), and fused to the reporter protein mRuby3. The constructs were evaluated in vitro using a fluorescent reporter system designed to provide a readout of TCR signaling upon the co-culture of T lymphocytes with differentiated monocytic cells expressing antigens. In vivo immunogenicity and protective efficacy were assessed in BALB/c (exploratory pilot) and IFNAR^−/− mice, a highly susceptible model for viral infection. Cytokine responses were measured to assess immunogenicity. Results: In vitro assays showed predominantly antigen-independent T-cell activation, suggesting that nonspecific stimulation inherent to the reporter co-culture system likely obscured the detection of antigen-specific TCR signaling. In vivo analyses in BALB/c mice revealed that the constructs elicited only modest systemic cytokine profiles while CCHFV-specific IgG and IFN-γ secretion remained undetectable, indicating that antigen-specific T-cell and antibody responses were limited. In the IFNAR^−/− challenge model, several peptide groups achieved significant 2–3 log reductions in tissue viral RNA and infectious titers (p < 0.05 vs. sham). However, the observed viral modulations were insufficient to reach the protective threshold and did not translate to a survival benefit (0%). Conclusion: Despite a rational in silico foundation, the multiepitope DNA vaccine constructs demonstrated limitations in inducing potent, antigen-specific immunity across both mouse models. The lack of antigen-specific responses indicates limitations in epitope selection, construct design, and delivery strategies, requiring optimization of next-generation epitope-based vaccines. These findings highlight the complexity of translating computational epitope predictions into functional vaccines, and provide benchmark data as a framework to guide future optimizations. Full article

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how miR-425 activates astrocytes, we found that, within astrocytes, miR-425 suppressed the expression of transcription factor ZNF24, which downregulated CCL8 cytokine expression/secretion, leading to the subsequent activation of astrocytes. Using a mouse study, we further determined the role of miR-425 in brain metastasis formation and observed that miR-425-overexpressing breast cancer cells exhibited significantly more aggressive growth in mouse brains compared to control cells. Immunohistochemistry and immunofluorescence analyses of mouse brain metastases revealed that miR-425-overexpressing tumors exhibited significantly increased activation, intratumoral accumulation, and proliferation of astrocytes, and a decrease in ZNF24 expression compared to control tumors. Together, our findings demonstrate, for the first time, that breast cancer EV-derived miR-425 promotes BCBM via activating astrocytes in the brain microenvironment through the novel EV-miR-425-ZNF24-CCL8 signaling axis. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. Methods: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. Results: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-α and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1β by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1β cytokines in the joints by 22% and 38%, respectively. Conclusions: These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning. Full article

Dang Gui (Radix Angelica sinensis), a classic Chinese medicinal herb, is renowned for nourishing blood, promoting blood circulation, regulating meridians, and relieving pain, and widely used clinically for anemia, cancer, rheumatoid arthritis, ulcerative colitis, and other diseases. Studies have confirmed that Dang Gui and its major bioactive components (e.g., polysaccharides, ferulic acid, (Z)-ligustilide) exert diverse pharmacological activities including immunomodulation, neuroprotection, and hepatoprotection. Based on a systematic literature search, this review summarizes the traditional applications and main chemical constituents of A. sinensis, with a focused analysis of its immunomodulatory effects. Evidence shows that A. sinensis exerts bidirectional immunoregulation by improving immune organ indices, promoting the proliferation and activation of immune cells, including T/B lymphocytes (T/B cells), macrophages, and regulating cytokine secretion. Furthermore, it reviews its immunomodulatory mechanisms in immune-related diseases (e.g., cancer, aplastic anemia, chronic pain), analyzes its quality control standards from regulatory and pharmacopeial perspectives and summarizes relevant safety research. This review comprehensively integrates the immunoregulatory effects and underlying mechanisms of A. sinensis, aiming to provide a scientific basis for its future research and clinical application. Full article

Osteoporosis is characterized by reductions in bone mineral density (BMD) and bone quality. While gut-derived signaling has been increasingly studied in relation to BMD, its contribution to molecular factors associated with bone quality remains less defined. Here, we investigated whether a heat-inactivated, freeze-dried, non-viable preparation of Levilactobacillus brevis AS-1 modulates intestinal epithelial-like cells and thereby promotes lysyl oxidase (LOX), a key enzyme involved in collagen cross-linking. Caco-2 cells were treated using 1 mM sodium butyrate and subsequently stimulated with 100 μg/mL L. brevis AS-1. Supernatants were collected and applied to MG63 cells. Cytokine mRNA expression in Caco-2 cells and LOX responses in MG63 cells were analyzed by qRT-PCR, and bone morphogenetic protein (BMP-1) and transforming growth factor-β (TGF-β)1 protein levels in the supernatant were measured by ELISA. L. brevis AS-1 stimulation up-regulated BMP-1 and TGF-β1 mRNA expression in SB-treated Caco-2 cells and increased BMP-1 protein secretion into the supernatant. LOX mRNA expression and total LOX activity were increased in MG63 cells treated with the conditioned supernatant, and inhibition of BMP-1/procollagen C-proteinase activity (UK383367) attenuated LOX mRNA induction. Collectively, these results suggest that L. brevis AS-1 stimulates intestinal epithelial-like cells to secrete BMP-1, which in turn promotes LOX mRNA expression in osteoblast precursor cells. This in vitro mechanism supports the concept of gut–bone crosstalk regulating molecular factors associated with bone quality. Full article

FAM3A, FAM3B, FAM3C and FAM3D are members of the “family with sequence similarity 3” (FAM3) gene family, an emerging class of cytokine-like proteins with a unique structural globular β-β-α fold and distinct biological functions. With widespread expression in tissue, organs and in many cell types, their specific roles in human diseases have been the focus of much research. FAM3A acts as a positive regulator of metabolic health, typically activating canonical pro-survival and metabolic pathways. FAM3B, also called PANDER (PANcreatic DERived Factor), exerts critical physiological functions in the regulation of glycemic levels via promotion of hepatic glucose production and pancreatic β-cell insulin secretion. FAM3C, also named ILEI (Interleukin-like EMT inducer), is involved as an inducer of epithelial–mesenchymal transition (EMT) and cancer metastasis, as well as osteoblast differentiation and bone mineralization. FAM3D is a gut-secreted protein and potential regulator of gastrointestinal homeostasis and microbiota-induced inflammation. Here we provide an overview of previous studies supporting that FAM3 proteins act through putative membrane receptors and co-partners, including fibroblast growth factor receptor (FGFR), leukemia inhibitory factor receptor (LIFR), formyl peptide receptor (FPR1/2), to activate diverse downstream signaling pathways on different cellular contexts. Basic and clinical studies suggest that the FAM3 family influences both obesity, diabetes, and other metabolic disorders; thus, its expression may have diagnostic potential. The differential and often cancer-specific expression patterns make members of the FAM3 family promising candidates for biomarkers and therapeutic targets of some types of neoplasia. Full article

Background/Objectives: Natural killer (NK) cells are key innate lymphoid cells that restrict tumour progression by secreting proinflammatory cytokines and directly lysing malignant cells, with their activity tightly regulated by a balance of activating and inhibitory surface receptors. The natural cytotoxicity receptor NKp44 is induced on NK cells following stimulation with IL-2 or IL-15 and recognizes platelet-derived growth factor D (PDGF-DD) as a ligand. Mechanistic interpretation of NKp44 signalling upon PDGF-DD engagement is confounded by the existence of three distinct NKp44 isoforms (NKp44-1, -2, and -3), each capable of initiating divergent intracellular signalling cascades. Unlike NKp44-2 and -3, NKp44-1 encodes a cytoplasmic tyrosine residue (Y238) that conforms to a putative immunoreceptor tyrosine-based inhibition motif (ITIM) and has been reported to suppress NK cell effector functions in some contexts. However, it remains unclear whether the NKp44 isoforms are translated and expressed in NK cells, and formal evidence defining NKp44-1 signalling in response to engagement by PDGF-DD is lacking. Methods: In this study, we used C-terminal targeting monoclonal antibodies (mAbs) and a NFAT-GFP reporter system to define the expression and signalling properties of NKp44 isoforms in response to PDGF-DD. Results: We demonstrate protein expression of NKp44-1 and NKp44-2-/3 receptors in IL-2 expanded NK cells. We further show that NKp44-1 transduces activating rather than inhibitory signals when engaged by PDGF-DD ligand, albeit weaker than NKp44-3. Intriguingly, we find that Y238 is dispensable for NKp44-1 activating signalling and instead functions as a YXXΦ internalisation motif. Conclusions: Collectively, these findings provide the first evidence that the NKp44-1 and NKp44-2/3 isoforms are expressed in NK cells and establish that PDGF-DD activates signalling through NKp44-1 independently of Y238. This work lays the foundations for future studies investigating how PDGF-DD sensing by the different NKp44 isoforms shapes immune functions in different physiological and pathological contexts. Full article

Ulcerative colitis (UC) is a multifactorial disease characterized by chronic intestinal inflammation and disrupted oxidative balance, significantly impairing patients’ quality of life. Tannins, a class of polyphenolic compounds widely distributed in plants, have demonstrated notable therapeutic potential against UC due to their inherent antioxidant and anti-inflammatory properties. This study employs a systematic literature review of databases, including PubMed and Web of Science, to investigate the molecular mechanisms by which tannins restore intestinal inflammatory and oxidative homeostasis. The findings indicate that tannins directly scavenge reactive oxygen species (ROS) via their polyphenolic structure, mitigate oxidative damage, upregulate antioxidant enzyme expression, suppress pro-inflammatory cytokine secretion, and preserve intestinal barrier integrity. Despite their significant therapeutic promise, challenges such as low bioavailability and structural complexity remain. Future research should prioritize bioavailability enhancement, clarification of structure-activity relationships, and translational studies to facilitate the clinical application of tannin-based therapies for UC. Full article

Atherosclerosis, the leading global cause of death, is a chronic inflammatory vascular disease with higher prevalence and earlier onset in men than in women. This study aims to investigate sex differences in the atherogenic endothelial phenotype during early atherosclerosis processes by providing the first comprehensive analysis of hormone-independent responses in human umbilical vein endothelial cells (HUVECs) from opposite-sex twins. HUVECs underwent pro-inflammatory stimulation with TNF-α and supernatant from activated pro-inflammatory THP-1 cells, revealing distinct sex-specific patterns: mRNA expression of focal adhesion proteins talin-I, vinculin, FAK, and α1-actinin increased significantly only in male cells, while paxillin showed elevated mRNA and protein levels in both sexes. Male HUVECs exhibited stronger induction of cell adhesion molecule VCAM-1, pro-inflammatory cytokine IL-1β, and proangiogenic factors Flt-3L, G-CSF, and PDGF-AA, whereas IL-22 secretion was exclusively upregulated in female cells. These sex differences in levels of focal adhesion, adhesion molecules, and cytokine profiles uncover the mechanistic backgrounds of the atherogenic endothelial phenotype, independent of systemic hormones. The findings emphasize cellular sex as a critical biological variable in early atherosclerosis and vascular inflammation. Full article