Search Results (373)

Background: There is growing interest in plant-derived compounds for managing vascular diseases. Veratramine (VRT), a steroidal alkaloid isolated from plants of the Veratrum genus, exhibits diverse biological effects such as antihypertensive, analgesic, and antitumor activities, yet its influence on hemostasis and thrombus formation has not been characterized. This investigation sought to determine whether VRT exerts anticoagulant effects using integrated in vitro and murine models. Methods: VRT’s anticoagulant profile was comprehensively evaluated using integrated biochemical, cellular, and murine models, including clotting time assays (aPTT/PT), chromogenic enzymatic assays, fibrin polymerization analysis, platelet aggregometry, and endothelial modulation of PAI-1/t-PA under inflammatory conditions. Results: VRT treatment significantly prolonged both intrinsic and extrinsic coagulation times, directly inhibited enzymatic activities of thrombin and FXa, and attenuated their generation by endothelial cells. Additionally, VRT interfered with fibrin clot formation and diminished agonist-induced platelet aggregation. Ex vivo coagulation analyses confirmed its anticoagulant action, while endothelial studies revealed a reduced PAI-1/t-PA ratio following VRT exposure. Conclusions: These data establish VRT as possessing novel direct dual inhibition of thrombin and FXa alongside suppression of fibrin polymerization, platelet reactivity, and PAI-1 expression—positioning it as a promising multifunctional anticoagulant agent. While preclinical murine models preclude direct clinical translation absent pharmacokinetic data, these findings warrant further mechanistic and translational investigation. Full article

Childhood obesity is a complex pathology that triggers early vascular damage through endoplasmic reticulum (ER) stress and fibrinolytic imbalance; however, the role of the ATF6/PLAT regulatory axis in this process has not yet been fully elucidated. This study aims to investigate the molecular basis of vascular risk by determining the expression levels of these genes and the potential regulatory hsa-miR-340-5p in children with obesity. Gene expression analyses were performed using the RT-qPCR method on blood samples obtained from 55 children with obesity and 40 healthy controls, while in silico protein–protein interaction (PPI) networks were mapped using the STRING database. The findings revealed that ATF6 expression was significantly downregulated (p < 0.001) and PLAT expression was significantly upregulated (p = 0.005) in the obese group compared to controls. No significant difference was detected in hsa-miR-340-5p levels (p = 0.447). PPI analysis confirmed the strong functional clustering of ATF6 with metabolic stress pathways and PLAT with coagulation cascades. In conclusion, the suppression of ATF6 in obesity indicates the “exhaustion” of adaptive cellular defense mechanisms, while the upregulation of PLAT points to a compensatory response to the chronic prothrombotic environment. These molecular alterations demonstrate that vascular risk in childhood obesity begins at the transcriptomic level long before clinical symptoms emerge, highlighting the ATF6/PLAT axis as a potential biomarker for early risk assessment. Full article

This review presents an innovative and timely exploration of how cytoprotection can serve as a cohesive therapeutic approach by which to address the hemorrhage–thrombosis paradox. Presenting counteraction of both hemorrhage and thrombosis as phase-dependent outcomes of vascular dysregulation, the manuscript synthesizes conceptual, experimental, and clinical evidence into a unified systems-level model focused on the stable gastric pentadecapeptide BPC 157, which acts as a cytoprotective mediator. In rodents, BPC 157 can simultaneously counteract hemorrhage and thrombosis without directly affecting the coagulation cascade (aggregometry, thromboelastometry). This cytoprotective framework (decreased hemorrhage, decreased thrombosis) stands with presentation of both hemorrhage and thrombosis in the wound, arrhythmias, and Virchow triad, and resolution of these disturbances. As proof of the concept (full cytoprotective effect), a vasoprotective cytoprotective mediator capable of bidirectional regulation, BPC 157, is effective for wound healing, arrhythmia control, and normalization of Virchow’s triad (i.e., following major injuries, occlusion/occlusion-like syndromes). As a comparison from a cytoprotective (partial vs. full) standpoint, conventional agents—anticoagulants, antiplatelet drugs, and fibrinolytics—provide only partial protection by targeting isolated components of hemostasis. Beta blockers, calcium channel blockers, prostaglandins, NO modulators, ACE inhibitors, and statins each exert broader cytoprotective effects; however, these actions remain incomplete and context-dependent, typically unidirectional, dose-limited, or are achieved at the expense of opposing pathological risks. Contrarily, for BPC 157, decreased hemorrhage (including both anticoagulants and antiplatelet agents), decreased thrombosis, effective wound healing, arrhythmia control, and normalization of Virchow’s triad involve preservation of endothelial integrity, normalization of microcirculation, modulation of the NO system, stabilization of hemostatic balance, and recruitment of adaptive collateral pathways. Nevertheless, reliance on preclinical models necessitates further clinical validation. Full article

Background/Objectives: To analyze possible epigenetic changes (miRNA) in systemic lupus erythematosus (SLE) patients on a Mediterranean diet (MD) supplemented with extra virgin olive oil (EVOO). Methods: Fifteen SLE patients with medium/high MD adherence were randomized into an intervention group (IG) (daily supplementation of 40 mL of EVOO for 24 weeks) or to a control group (CG). miRNA profiles from blood peripheral cells were analyzed pre-/post-intervention using next-generation sequencing. Differential expression analysis was performed by DESeq2 in R to determine changes in the log2FC. Functional enrichment analysis was performed using GeneCodis 4. Results: EVOO supplementation resulted in changes in the expression of 16 miRNAs in the IG. Compared to the CG, two miRNAs showed upregulation (miR-451a, miR-1307-5p) while five showed downregulation (miR-193b-50, miR-134-5p, miR1287-5p, miR-124-3p, miR-654-3p). miR-124-3p, which has been proposed to be an SLE biomarker, showed the lowest relative expression after EVOO supplementation (L2FC −3.36; p_unadj = 0.025), whereas miR-1307-5p (L2FC 1.115 p_unadj = 0.02) and miR-451a (L2FC 0.77 p_unadj = 0.036) showed the highest relative abundance. The functional enrichment analysis showed that Th1 and Th2 cell differentiation and the complement/coagulation cascades were among the top ten most significantly enriched pathways. Conclusions: Our data suggest that MD supplementation with EVOO leads to changes in the profile of miRNAs in SLE patients, potentially impacting disease pathogenesis. Further research is needed to validate these preliminary findings and the mechanisms by which EVOO modifies miRNA expression in the context of this disease. Full article

Endothelial cells are key regulators of vascular homeostasis, and their dysfunction plays a central role in the development of atherosclerosis and other cardiovascular diseases. Multinucleated variant endothelial cells (MVECs) have been described in pathological vascular regions; however, their functional properties remain poorly characterized. The aim of the present study was to compare lipid handling, inflammatory activation, barrier-associated features, and secretory profiles of typical endothelial cells (TECs, EA.hy926 line) and MVECs under low-density lipoprotein (LDL) exposure. MVECs were generated by polyethylene glycol-induced fusion of EA.hy926 cells and incubated with LDL under standardized conditions. Intracellular cholesterol accumulation was assessed biochemically, cytokine secretion was quantified by ELISA, gene expression of inflammatory, endothelial, junctional, and vasoactive markers was analyzed by quantitative real-time PCR, and the endothelial secretome was characterized using data-independent acquisition liquid chromatography–tandem mass spectrometry (DIA-LC-MS). MVECs demonstrated enhanced cholesterol accumulation compared with TECs following LDL exposure. At the transcriptional level, MVECs were characterized by elevated basal expression of proinflammatory markers, including IL1B, IL6, and NFKB1, and showed a markedly amplified IL6 and IL8 response to LDL. In parallel, MVECs exhibited reduced expression of genes associated with antioxidant defense (SOD1), barrier integrity (TJP1), and hemostatic function (VWF). Consistent with transcriptional data, mass spectrometry-based secretome analysis revealed decreased secretion of von Willebrand factor (vWF), vascular endothelial growth factor C (VEGFC), and endothelin-1 (EDN1) by MVECs, accompanied by increased secretion of tissue-type plasminogen activator (t-PA). Functional enrichment analysis of secretome-associated proteins highlighted pathways related to extracellular matrix–receptor interaction, focal adhesion, cell adhesion molecules, complement and coagulation cascades, and leukocyte transendothelial migration. In contrast, TECs demonstrated a more pronounced transcriptional response in EDN1, consistent with their role in vascular tone regulation. Immunocytochemical analysis further revealed altered subcellular distribution of the tight junction protein ZO-1 in MVECs, indicating junctional destabilization. Taken together, these results indicate that MVECs represent a distinct endothelial phenotype characterized by enhanced lipid accumulation, sustained proinflammatory activation, altered secretory signaling, and reduced barrier and hemostatic potential. Such features suggest that MVECs may contribute to the maintenance of chronic endothelial dysfunction and vascular inflammation under conditions of lipid overload. Full article

Background and Objectives: Post-COVID-19 syndrome (PCS), characterized by persistent fatigue, can develop after a SARS-CoV-2 infection. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, post-infectious condition marked by severe fatigue and post-exertional malaise. This study aimed to determine the incidence and characteristics of PCS and ME/CFS in a cohort of hospital employees (HEs) with SARS-CoV-2 infections. Materials and Methods: All HEs who tested SARS-CoV-2-positive between March 2020 and May 2021 who later reported persistent fatigue were invited for an assessment from July to December 2022. Canadian Consensus Criteria were used for the diagnosis of ME/CFS. Assessments included the Montreal Cognitive Assessment (MoCA), and determination of coagulation factors, Epstein–Barr virus (EBV) antibodies and autoantibodies (AABs) against G-protein-coupled receptors (GPCRs). Results: Of the 221 HEs, 11.8% (95% confidence interval (CI95%) 7.8–16.8, 26/221) still reported persistent fatigue and 3.2% (CI95% 1.3–6.4, 7/221) were diagnosed with ME/CFS. In total, 19 HEs (median age 51.0 years, 89.4% female, 63.1% possible or confirmed nosocomial infection) participated in our assessment. In 42.1% (8/19) MoCA results were below normal. Laboratory values showed increased GPCR AABs in 66.6% (12/18), possible EBV reactivation in 86.7% (13/15) and coagulation parameters suggesting inflammatory processes in 38.9% (7/18). Conclusions: Our study was able to determine lower-bound incidences of PCS with fatigue and ME/CFS and demonstrated a diagnostic pathway for HEs following SARS-CoV-2 infections. Possible EBV reactivation, increased GPCR AABs and potential coagulation cascade activation may play a pathogenic role. Full article

Cerebral Cavernous Malformations (CCMs) are low-flow vascular lesions located within the central nervous system, with a reported prevalence in the general population of 0.16–0.5%. Patients with CCMs may remain asymptomatic or present new onset symptoms such as seizures or focal neurological deficits often related to the occurrence of intracerebral hemorrhage. CCM may appear sporadic or as part of familial forms linked to mutations in the CCM-gene cluster, affecting endothelial cell integrity and triggering molecular cascades, including the MEKK3/KLF2/4 signaling pathway. Recent studies have highlighted the roles of inflammatory, angiogenic, and coagulation pathways alongside the emerging evidence of a gut–brain axis influencing microbiome-driven TLR4 signaling. This systematic review aims to describe molecular biomarkers associated with CCM pathophysiology, emphasizing their potential use as diagnostic and prognostic tools. Circulating plasma biomarkers such as CRP, vitamin D, and interleukins may reflect ongoing inflammatory and endothelial processes, while some imaging biomarkers like Quantitative Susceptibility Mapping (QSM) have shown a correlation with iron deposition and vascular leakage. Leveraging both circulating and imaging biomarkers may improve the therapeutic decision-making process. Further studies are encouraged to validate these findings and to facilitate the development of personalized, evidence-based strategies for the management of CCM. Full article

Despite significant advances in neurosurgical and critical care, traumatic brain injury (TBI) remains a major cause of morbidity and mortality. Surgical treatment of intracranial hemorrhagic lesions can only target the primary mechanical injuries and their immediate consequences but fails to address the biochemical pathological cascade that unfolds during the second injury. This review synthesizes current knowledge regarding the use of several biomarkers in diagnosis and prognosis assessment. A structured literature search was conducted by querying the PubMed database. Articles evaluating diagnostic and prognostic biomarkers in adult TBI were screened according to Prisma guidelines, and data regarding biomarkers type, cut-off values, and correlations with the outcome were extracted and summarized. Among Central Nervous System (CNS)-Specific markers, S100 calcium-binding protein (S100B) emerged as a remarkably strong negative predictor for Computed Tomography (CT)-visible intracranial lesions (NPV = 97.3–100%), whereas glial fibrillary acidic protein (GFAP) yielded both high NPV and brain specificity. Coagulation parameters such as the international normalized ratio (INR) and fibrinogen were independently correlated with mortality and unfavorable outcomes. Fibrinogen displayed a bidirectional relationship with increased mortality risk at both low (<2 g/L) and high (>4.5 g/L) values. In conclusion, biomarkers quantify the otherwise invisible progression of secondary traumatic brain injury that persists even after successful surgery. Full article

Imperfect first-trimester screening for hypertensive disorders of pregnancy (HDP) means many high-risk women miss the window for preventive aspirin, and the biological heterogeneity of HDPs is overlooked. This study aimed to leverage first-trimester serum proteomics to create a more precise tool for predicting preeclampsia (PE) and differentiating it from other HDPs. A prospective nested case–control study (n = 172) was conducted using targeted liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) proteomic profiling of 115 proteins. Machine learning (ML) methods were used to develop classifiers from the proteomic data. The signature predictive of PE was characterized by dysregulation of the complement and coagulation cascades (F10, C8A, C1QA, SERPING1, VTN). The profile differentiating gestational hypertension (GAH) from chronic hypertension (CAH) was linked to lipid metabolism (HRG, APOA4, APOC2). An 18-protein support vector machine (SVM) model for predicting PE demonstrated exceptional performance, with 94% sensitivity and 100% specificity, significantly outperforming the standard Fetal Medicine Foundation (FMF) screening algorithm. Pathway analysis confirmed that PE is associated with early activation of innate immunity and coagulation pathways, while GAH is linked to a pregnancy-induced metabolic response. A targeted serum proteomic combined with ML approach represents a new perspective diagnostic tool with strong potential to personalize monitoring for women at the highest risk for specific hypertensive pregnancy complications. Full article

Oral mucosa healing is a complex process that involves the innate wound healing system, including the coagulation cascade, extracellular matrix remodeling, immune cell responses, and fibroblast and epithelial responses, within the context of a dynamic resident microbiome. Unlike cutaneous wounds, oral wounds heal rapidly with minimal scarring despite constant exposure to diverse microbial communities, saliva, and mechanical stress. Emerging evidence highlights the critical interplay between microbiome-mediated signaling and macrophage plasticity in shaping wound outcomes, suggesting that similar mechanisms operate within the oral cavity. Inflammation is an essential component of wound repair, and its resolution is necessary to promote tissue remodeling and functional regeneration. Macrophages play a central role in this transition through phenotype switching from a pro-inflammatory (M1) to a pro-resolving, anti-inflammatory (M2) state. This review synthesizes current understanding of the oral microbiome’s influence on macrophage polarization across distinct stages of oral wound healing and examines microbial-based strategies that modulate the immune response to enhance repair. Significant knowledge gaps remain, including limited clinical translation, inter-individual variability in microbiome composition, and complete mechanistic insight into host–microbe immune interaction. Addressing these challenges enables the development of precision microbiome-based therapeutics that restore microbial balance, direct macrophage-driven regeneration, and improve outcomes in oral wounds and chronic inflammatory conditions. Full article

Fiber-forming polymers are increasingly used to control blood coagulation, either by accelerating the onset of hemostasis or by limiting thrombogenic events in contact with blood. Despite rapid progress in materials engineering, a unified view linking the molecular mechanisms of the coagulation cascade with specific design strategies of procoagulant and anticoagulant polymeric fibers is still missing. In this review, we summarize current knowledge on how natural and synthetic polymers interact with plasma proteins, platelets, and coagulation factors, emphasizing the role of fiber morphology, surface chemistry, charge distribution, and functionalization. Particular attention was paid to systems based on natural polysaccharides (e.g., chitosan, alginate, and cellulose derivatives), as well as synthetic polymers (e.g., PLA, PCL, polyurethanes, and zwitterionic materials). Two possible courses of action were described: their bioactivity may activate the contact pathway and/or support platelet adhesion or their ability to minimize protein adsorption and inhibit thrombin generation. We discuss how metal–polymer coordination, surface immobilization of heparin or nitric oxide donors, and nanoscale texturing modulate coagulation kinetics in opposite directions. Finally, we highlight emerging fiber-based strategies for achieving either rapid hemostasis or long-term hemocompatibility and propose design principles enabling precise tuning of coagulation responses for wound dressings, vascular grafts, and blood-contacting devices. This general compendium of knowledge on blood–material interactions provides a foundation for further design of biomaterials based on fiber-forming polymers and the development of manufacturing processes. Full article

The introduction of direct oral anticoagulants (DOACs), particularly factor Xa (FXa) inhibitors, has transformed the prevention and treatment of thromboembolic events. These agents have largely replaced vitamin K antagonists across most indications due to their predictable pharmacokinetics, reduced rates of intracranial bleeding, and overall ease of use. Nevertheless, a substantial residual bleeding risk remains, particularly gastrointestinal bleeding and clinically relevant non-major bleeding in elderly, frail, or polymedicated patients. Furthermore, the management of patients with severe renal dysfunction, active cancer, especially gastrointestinal or genitourinary malignancies and those requiring complex pharmacological regimens, continues to pose significant challenges. These limitations have intensified interest in targeting earlier steps of the coagulation cascade, specifically factor XI (FXI) and its activated form (FXIa). FXI occupies a unique mechanistic position: it contributes substantially to pathological thrombosis while playing only a limited role in physiological hemostasis. Genetic, observational, and mechanistic evidence consistently demonstrates that FXI deficiency confers protection against venous thromboembolism and cardiovascular events while causing minimal spontaneous bleeding. This biological paradigm has catalyzed the development of novel FXI/FXIa inhibitors, including small-molecule agents (asundexian, milvexian) and biological therapies (abelacimab). Clinical trials such as AXIOMATIC-TKR, PACIFIC-AF, and OCEANIC-AF, and ongoing programmes including ASTER and MAGNOLIA suggest that FXI inhibition may preserve antithrombotic efficacy while substantially reducing bleeding risk. This review summarizes the current landscape of oral FXa inhibitors, outlines the biological rationale for FXI/FXIa inhibition, and discusses the evolving clinical evidence supporting what may represent the next major advance in anticoagulant therapy. Full article

In this work, kaolin/chitin (K/Ch) composite aerogels with different mass ratios were successfully fabricated via a freeze–drying approach. The influence of kaolin content on the microstructure, properties and hemostatic performance of the composite aerogels was systematically investigated. The results demonstrated that the incorporation of kaolin endowed the chitin-based aerogels with tunable porous structures, excellent water absorption capacity (up to 4282% for K_0.25/Ch₂), and enhanced water retention (73.7% for K₂/Ch₂ at 60 min). Moreover, the K/Ch composite aerogels exhibited good biodegradability, no cytotoxicity (cell viability > 91.9%), and no hemolysis (hemolysis rate < 1.5% at all test concentrations). In vitro hemostatic evaluations revealed that the composite aerogels exhibited rapid blood coagulation (blood clotting time of 16 s for K₂/Ch₂) with a blood coagulation index (BCI) as low as 0.5%, which was attributed to the synergistic effect of the physical adsorption of chitin and the coagulation cascade activation by kaolin. These findings indicated that the K/Ch composite aerogels could be used as novel natural hemostatic materials for potential effective and rapid hemostasis. Full article

This study tackles the challenge of treating high-oil (≥90 mg/L) and high-salinity (Cl⁻ ≥ 6900 mg/L) oilfield-produced water for green hydrogen production. An integrated technology combining electrochemical cascade purification (EDCF: electro-demulsification–coagulation–flotation) with alkaline water electrolysis is developed. The EDCF process effectively reduces oil, suspended solids, and turbidity to <10 mg/L, <20 mg/L, and <20 NTU, respectively, meeting stringent feedwater criteria for electrolysis. An asymmetric electrolysis strategy employing a nickel felt anode/Raney nickel cathode system achieves a low cell voltage of 1.856 V at 1 A/cm² in 6 M KOH at 85 °C, with 96.58% H₂ purity. Crucially, separate anolyte/catholyte (0.5/6 M KOH) mitigates Cl⁻ corrosion, enabling stable 240 h operation (96.66% ± 0.5% H₂ purity) in a duplex steel electrolyzer. The work establishes comprehensive boundary conditions for scalable hydrogen production from treated produced water. Full article

Damage-associated molecular patterns (DAMPs) are endogenous molecules released during cellular stress or injury that trigger sterile inflammation. In perioperative settings, common triggers include surgical trauma, ischemia–reperfusion injury, cardiopulmonary bypass, blood transfusion, and mechanical ventilation. When released extracellularly, DAMPs activate innate immune receptors such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), initiating signaling cascades that amplify inflammation, disrupt endothelial integrity, and promote coagulation and metabolic imbalance. This sterile inflammatory response may extend local tissue injury into systemic organ dysfunction, manifesting clinically as acute lung injury, acute kidney injury, myocardial dysfunction, disseminated intravascular coagulation, and perioperative neurocognitive disorders. Recognizing the central role of DAMPs reframes these complications as predictable consequences of endogenous danger signaling rather than solely as results of infection or hemodynamic instability. This understanding supports the use of established strategies such as protective ventilation and restrictive transfusion to minimize DAMP release. Emerging evidence also suggests that anesthetic agents may influence DAMP-mediated inflammation: propofol and dexmedetomidine appear to exert anti-inflammatory effects, whereas volatile anesthetics show variable results. Although clinical data remain limited, anesthetic choice and perioperative management may significantly affect systemic inflammatory burden and recovery. Future research validating DAMPs as biomarkers and therapeutic targets may inform precision anesthetic strategies aimed at modulating sterile inflammation, ultimately enhancing perioperative outcome. Full article