Search Results (350)

Background/Objectives: Syringa vulgaris L. (common lilac) is one of the most popular ornamental plant species. Through the ages, many parts of S. vulgaris, including fruits, flowers, leaves, and branches, have been used in folk medicine due to their beneficial biological activity. Lilac flowers are the basis of many supplements available on the market. Moreover, its petals and flowers are edible and are an aromatic ingredient in preserves and desserts. However, the data about the antioxidant properties of various parts of S. vulgaris is limited only to the in vitro antioxidant capacity of the extracts—so far, the effect of S. vulgaris flower extract on the parameters of oxidative stress in biological materials, including plasma, has not been demonstrated. Therefore, the aim of our study was to investigate the protective effects of the extract from S. vulgaris L. flowers against oxidative stress in human plasma, and its influence on the coagulation process in vitro. Methods: We measured the levels of three parameters of oxidative stress in human plasma treated with H₂O₂/Fe²⁺ (the donor of hydroxyl radicals): lipid peroxidation (based on the level of thiobarbituric acid reactive substances (TBARS)), protein carbonylation, and thiol oxidation. Ascorbic acid (vitamin C) was used as a reference antioxidant. In addition, we studied the effect of the extract on three coagulation parameters of human plasma-activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). We also compared the biological properties of the extract from S. vulgaris flowers with the properties of a phenolic extract from Taraxacum officinalis (dandelion) flowers, as they have proven antioxidant activity in both in vitro and in vivo models and can modulate hemostasis in vitro. Results: Our UHPLC-HRMS analyses of S. vulgaris extract led to a tentative identification of 50 compounds, mainly phenolics and secoiridoids. For the first time, the present study demonstrated that the extract from S. vulgaris flowers (at the concentrations of 1–50 µg/mL) significantly reduced plasma lipid peroxidation and protein carbonylation induced by H₂O₂/Fe²⁺. Moreover, the concentrations of 1–25 µg/mL significantly reduced the oxidation of thiol groups in plasma treated with H₂O₂/Fe²⁺. The anticoagulant tests also demonstrated that S. vulgaris flowers extract, at physiologically relevant concentrations (1–50 µg/mL), did not affect blood clotting times in vitro, suggesting that it is hemostatically safe. Conclusions: Despite the differences in composition, the extracts from lilac flowers and dandelion flowers exhibited similar protective effects against oxidative damage to human plasma components. However, the extract from S. vulgaris flowers had a stronger inhibitory effect on lipid peroxidation than the extract from dandelion flowers. Full article

Intracerebral hemorrhage (ICH) remains a devastating condition with no available therapies that can effectively mitigate secondary injury and promote neurological repair. This research presents a novel combinatorial regenerative strategy, concurrently delivering adipose-derived stromal vascular fraction (SVF) within an adhesive self-assembling peptide (HGF-RADA16-IKVAV) nanohydrogel (HGF). In a clinically relevant rat model of ICH with hematoma evacuation, the combined therapy of HGF and SVF demonstrated synergistic and enhanced efficacy. In the short term, the combined therapy demonstrated hemostatic benefits, and significantly reduced hematoma volume, brain edema, neuronal apoptosis and neuroinflammation indicated by pro-inflammatory markers (NLRP3, caspase-1, Iba-1, CD68, GFAP) while increasing the levels of anti-inflammatory (CD206) and angiogenic (CD31) markers. Longitudinal behavioral assessments conducted over six weeks demonstrated persistent and significant improvements in motor coordination, forelimb strength, and gait parameters within the HGF + SVF group, surpassing all monotherapies. Ultrastructural analysis also showed that myelinated axons were better preserved at the injury border, with thicker myelin sheaths. These findings demonstrate that the co-administration of SVF with an adhesive and hemostatic hydrogel collaboratively diminishes secondary injury, modulates neuroinflammation, and promotes functional and structural brain recovery following ICH, indicating a promising and translatable strategy. Full article

Background/Objectives: Achieving effective hemostasis is a vital step in wound healing, particularly in cases of severe bleeding caused by surgical procedures or trauma. This study focuses on the development of chitosan-based dressings enriched with Heparin (hep)-loaded poly(butylene succinate) (PBSu) nanoparticles to combine hemostatic and anticoagulant properties. Methods: Chitosan, a biocompatible and biodegradable carbohydrate with inherent antibacterial and hemostatic properties, was chemically modified with 2-(N-morpholino)ethanesulfonic acid (MES) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) to enhance its swelling ability and hemostatic activity. PBSu nanoparticles were synthesized using an oil-in-water emulsification method and loaded with Hep to achieve controlled anticoagulant release. The dressings of the modified chitosan derivatives with the nanoparticles which were systematically characterized for morphology, chemical structure, swelling ability, loading capacity, and Hep release kinetics. Results: This dual-function system is designed to decouple local surface hemostasis from thrombotic processes: the chitosan matrix provides rapid topical hemostasis, while controlled heparin release from the nanoparticles aims to modulate excessive fibrin deposition, support microvascular perfusion, and exploit the pro-healing benefits of low-dose heparin reported in advanced wound dressings, particularly in high-risk or thrombotic-prone patients. In vitro and in vivo studies demonstrated their potential for promoting rapid hemostasis. Conclusions: These findings suggest that the integration of modified chitosan and Hep-loaded nanoparticles is a promising strategy for advancing wound care and hemostatic technologies. Full article

Background/Objectives: Total knee arthroplasty (TKA) is often associated with extensive bleeding and the need for intraoperative and postoperative blood transfusions. Due to concern about the risks associated with them, a push has been made in surgery toward the development of new intraoperative blood management devices and innovative postoperative care strategies. Tranexamic acid (TXA), fibrin sealant and standard electrocautery are widely used in orthopedic surgery, since several studies provided evidence about their efficacy and safety. A new device, the bipolar sealer system (BSS), provides hemostasis at lower temperature (<100°) than conventional electrocautery. It does not produce smoke, necrosis or burn tissue. Methods: In this study, we retrospectively analyzed data from 480 patients who underwent TKA between January 2017 and December 2024. The cohort was divided into two groups based on the hemostatic protocol adopted. The control group enrolled 240 patients who received the standard protocol with TXA and fibrin sealant, while the study group enrolled 240 patients who followed protocol with Aquamantys BSS and TXA. Hematological parameters, including hemoglobin (Hb), hematocrit (HCT) and red blood cells (RBCs) were analyzed preoperatively (T0) and postoperatively: immediately after surgery (T1), at day one (T2) and day three (T3). Results: Changes in hemoglobin from baseline to postoperative follow-up were significantly lower among patients who received TXA plus BSS and those receiving TXA plus fibrin sealant, with p-values of 0.0003 at T1 (immediately after surgery), 0.027 at T2 (one day post-op), and 0.0001 at T3 (three days post-op). Comparable results were observed for HCT and RBC values. Conclusions: These data demonstrate that Aquamantys is more effective than fibrin glue in controlling blood loss after knee replacement surgery, not only immediately after the procedure but also in the following days. Full article

Background: Nasopharyngeal carcinoma diagnosis requires endoscopic biopsy, but intraoperative hemorrhage frequently impairs visualization and compromises tissue sampling quality. This prospective case series evaluated topical tranexamic acid (TXA) as a hemostatic adjunct to improve biopsy conditions in suspected nasopharyngeal malignancy. Methods: Adults (≥18 years) with clinically/radiologically suspected nasopharyngeal tumors underwent pre-biopsy laboratory screening and exclusion of thromboembolic risk factors. After topical lidocaine anesthesia, a TXA-soaked cotton pledget was applied to the lesion for 10 min prior to forceps biopsy using 0° 4 mm endoscopy. Bleeding severity was graded pragmatically (minimal: ≤3 gauze pledgets; moderate: >3 or cauterization). Comparative analyses excluded rare diagnoses (n = 1). Results: Of 40 enrolled patients, 34 underwent biopsy (mean age 58.4 ± 12.3 years). All 34 biopsies (100%) yielded conclusive histopathological diagnoses. Adequate hemostasis was achieved in 97.1% (33/34), with minimal bleeding in 76.5% and moderate/massive in 23.5%. Non-keratinizing squamous cell carcinoma (44.1%) showed higher moderate bleeding rates than other diagnoses (Fisher’s exact p = 0.00035). Mean hospitalization was 1.79 ± 1.92 days, uniform across categories. No TXA-related adverse events occurred. Conclusions: Topical TXA provided safe, effective hemostasis during nasopharyngeal biopsy across diverse pathologies, achieving 100% diagnostic adequacy and short hospital stays. Controlled trials comparing TXA versus standard hemostatic techniques are warranted. 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

Bone regeneration focuses on the creation of functional tissue to repair bone defects. Creating a biodegradable scaffold hydrogel that combines a hemostatic agent with bioactive ceramics can afford the biological and mechanical benefits of both components. In the present study, we developed an injectable gelatin–alginate dual-composite hydrogel, loaded with two functional fillers: hydroxyapatite (HA) and the hemostatic agent montmorillonite (MMT). HA (microparticles and nanoparticles) was incorporated at concentrations of 10–30 mg/mL, with and without MMT at 20 mg/mL. The effects of functional fillers and their concentration on the microstructure and resulting physical and mechanical properties were studied, and a qualitative model summarising these effects was developed. All formulations exhibited clinically appropriate gelation times (5–29 s). n-HA significantly prolonged gelation time, reaching 29 ± 3 s at 30 mg/mL, while MMT reduced gelation time at all concentrations. The tensile strength of the unloaded hydrogel reached 20 kPa and increased to 57 kPa with 30 mg/mL of n-HA. The tensile strength even increased further with the addition of MMT (77 kPa). The results indicate that the combination of HA and MMT produced dual micro-composite hydrogels with moderate reinforcement, whereas the combination of n-HA and MMT generated dual nano–micro composites with combined reinforcing effects. The latter exhibited the highest strength and sealing ability while maintaining clinically relevant gelation times and controlled swelling behaviour. In conclusion, the combination of MMT with n-HA or HA enables the creation of functional hydrogels with controlled properties, tailored to specific applications in bone regeneration. Full article

WIB-801CE, a standardized Cordyceps militaris extract containing 7.0% cordycepin, suppresses platelet activation induced by thrombin, collagen, and adenosine diphosphate (ADP). As these agonists generate thromboxane A₂ (TXA₂), which amplifies platelet activation via a self-propagating feedback loop, blockade of TXA₂-mediated signaling offers strong antithrombotic potential. TXA₂-antagonistic effects were evaluated using U46619, a stable TXA₂ analog. Platelet activation was assessed by fibrinogen binding to integrin αIIbβ₃, aggregation, and phosphorylation of platelet-activating proteins—PI3K (Tyr458), Akt (Ser473), p38 MAPK (Thr180/Tyr182), ERK1 (Thr202/Tyr204), JNK1 (Thr183/Tyr185)—and inhibitory proteins—VASP (Ser157) and IP₃RI (Ser1756)—via immunoblotting. Thrombin-induced fibrin clot retraction, cytotoxicity, coagulation parameters, and antioxidant capacity were also examined. WIB-801CE significantly inhibited U46619-induced fibrinogen binding to integrin αIIbβ₃ and platelet aggregation, without inducing cytotoxicity or impairing hemostatic function. It also significantly downregulated the phosphorylation of platelet-activating proteins and upregulated the phosphorylation of platelet-inhibiting proteins. Additionally, WIB-801CE abolished thrombin-induced fibrin clot retraction and demonstrated antioxidant capacity. WIB-801CE disrupts TXA₂-driven platelet activation and thrombus stabilization by selectively modulating phosphorylation of key signaling proteins at defined regulatory sites. These properties highlight its promise as a therapeutic candidate for thrombotic disorders with platelet hyperreactivity. Full article

Developing safe and effective hemostatic materials is critical for rapid bleeding control and wound management. However, traditional hemostatic materials using chemical crosslinking often fall short in hemostatic efficiency and carry risks of secondary injury from reagent residues. This study introduced an irradiation-fabricated composite collagen sponge based on fish skin collagen, chitosan, and soluble starch. The sponge was prepared via material solution blending, followed by cobalt-60 gamma irradiation at various doses, with casting and freeze-drying. Its functionality and safety were systematically evaluated. The results show that low-dose gamma irradiation (1–3 kGy) applied to a precursor solution prior to freeze-drying promoted intermolecular crosslinking, improving mechanical strength, elongation, and biostability, while higher doses (6 kGy) slightly reduced crosslinking due to the partial degradation of collagen, chitosan, and starch. With low-dose irradiation, the proposed hemostatic sponges show enhanced water absorption, blood cell adsorption, swelling, and antibacterial properties, indicating effective hemostatic performance. Spectroscopic characterization confirmed chemical bond modifications with no loss of crystallinity. Cytotoxicity and in vivo tests demonstrated biocompatibility and effective hemostatic performance. Compared with the commercial HSD sponge, the irradiated sponges exhibited superior hemostatic efficacy. This study presents that a collagen-based synergistic matrix prepared by gamma-ray irradiation can produce a hemostatic sponge with enhanced absorbency, bioactivity, and antibacterial properties, highlighting its great potential in rapid hemostasis and wound care applications. Full article

Diabetic foot ulcers (DFUs) are wounds characterized by chronic inflammation and elevated oxidative stress that delay tissue regeneration and render them susceptible to infection, thereby complicating healing. Therefore, treating DFUs effectively is often challenging and requires a combined approach that integrates anti-inflammatory, antioxidant, and antibacterial effects. Curcumin, a widely studied natural compound, has shown promise in wound healing by modulating inflammation, oxidative stress, and infections. However, its bioavailability, absorption, and solubility issues limit its clinical applications. To overcome these limitations, curcumin has been incorporated into nanosystems, such as hydrogels, nanofibers, nanoparticles, vesicles, and micelles, thereby improving its delivery and enabling efficient local administration. Among these nanosystems, those formulated with chitosan are of particular interest due to chitosan’s intrinsic wound-healing properties. For that reason, this review comprehensively analyzes the literature on the therapeutic mechanisms of the chitosan–curcumin system for diabetic wound closure and compares them with those of free curcumin. The results show that this system exerts anti-inflammatory, antioxidant, and antimicrobial effects through specific mechanisms, including macrophage polarization, modulation of oxidative stress, and alteration of bacterial cell walls. In addition, significant improvements are observed in key healing processes, including cell migration, fibroblast proliferation, collagen deposition, and re-epithelialization. It should be noted that chitosan not only promotes curcumin release but also contributes to its therapeutic effect through its inherent antimicrobial and hemostatic properties, reinforcing its potential as a comprehensive strategy for the treatment of DFUs. Full article

Malignancy-related gastrointestinal bleeding (GIB) remains a significant clinical challenge, contributing substantially to morbidity, mortality, and healthcare utilization in patients with cancer. Up to 10% of individuals with advanced malignancies develop GIB during their disease, and these episodes are frequently characterized by a high risk of rebleeding and poor long-term hemostatic control. Tumor-associated bleeding typically arises from friable, infiltrative, and highly vascular lesions that respond suboptimally to conventional endoscopic techniques such as thermal coagulation or mechanical clipping. These limitations underscore the need for improved diagnostic accuracy and more reliable therapeutic options. Recent advances in imaging modalities, including contrast-enhanced CT studies, have enhanced the ability to localize and characterize bleeding sources in complex oncologic cases. Parallel developments in endoscopic hemostasis—such as over-the-scope clips and contact-free coagulation devices—have expanded the therapeutic armamentarium for managing malignant bleeding. Clinically, topical hemostatic powders—particularly TC-325—represent a highly effective option for achieving rapid endoscopic hemostasis, supported by the strongest comparative evidence and the highest rates of immediate bleeding control among currently available technologies. In this review, we synthesize contemporary diagnostic approaches to GIB and place particular emphasis on the evolving and emerging therapeutic strategies for malignancy-related bleeding. We also highlight innovative technologies that are reshaping clinical practice and improving management options in this challenging clinical domain. Full article

Background: Embolization is a key therapeutic option in interventional radiology for the management of acute arterial bleeding and solid organ injuries. While various embolic agents exist, there is a persistent clinical need for materials that are not only highly effective but also biocompatible, easy to deliver, and cost-effective. We aim to evaluate a new eco-friendly dry foam agar-based embolization agent (ABEA) in an uncontrolled solid organ hemorrhage model. Material and Methods: Ten pigs underwent a controlled splenic injury. After a 5 min free-bleeding period, five pigs were treated with splenic artery ABEA embolization, while the remaining five received no treatment and served as the control group. Follow-up angiography was performed immediately after embolization and at 5 and 15 min in the treated pigs. Mean arterial pressures and average blood loss volumes were evaluated for 120 min. Results: The control group showed continuous blood loss, leading to a significantly higher total blood loss than the ABEA-treated group (1451 mL vs. 611 mL at 120 min, p < 0.05). Mean arterial pressure (MAP) remained below the hemorrhagic shock threshold throughout the procedure in the control group, validating the model of uncontrolled hemorrhage. In addition, a significant stabilization of MAP was observed in treated pigs, remaining above the critical level of hemorrhagic shock and differed significantly from control group values. Conclusions: Embolization with ABEA maintained MAP above critical levels and significantly reduced blood loss volume in a hemorrhagic model. These results support the technical feasibility and short-term hemostatic performance of ABEA in an acute setting. While preliminary, this proof-of-concept has provided the basis for a validated clinical study currently underway to evaluate its effectiveness and safety in human patients. Full article

Phenolic acids of plant origin are recognized as key bioactive compounds with potential for both internal and topical applications. Although some of these phytochemicals are used for skin care and to improve wound healing, oligomeric derivatives of rosmarinic acid (RA) remain poorly characterized in this context. This study aimed to evaluate the anti-inflammatory potential of salvianolic acid H (SA H) and yunnaneic acid B (YA B) in experimental models related to wound-healing, specifically in skin cells (HaCaT keratinocyte and NHDF fibroblast lines), THP1-ASC-GFP monocytes, and human peripheral blood mononuclear cells (PBMCs). Both SA H and YA B reduced pro-inflammatory cytokine release from HaCaT, NHDF, and PBMCs with efficacy comparable to or exceeding that of RA. Analyses of intracellular pathways of inflammatory response revealed that SA H and YA B were also efficient inhibitors of inflammasome formation in THP1-ASC-GFP reporter cells. Furthermore, SA H showed significant inhibitory effects on the activities of cyclooxygenase-2 and 5-lipoxygenase (IC₅₀ = 11.53 µg/mL and 2.41 µg/mL, respectively). None of the examined acids influenced the hemostatic system at concentrations of 1–5 μg/mL. At 50 μg/mL, a slight increase in plasma clotting rate was observed for SA H and RA. These findings indicate that SA H and YA B, two naturally occurring oligomeric derivatives of RA, exert significant anti-inflammatory activity and represent promising agents for further studies on their use to improve wound healing. Full article

Hemostatic biomaterials are widely used in surgical and trauma settings, yet their influence on early wound healing remains incompletely understood. This in vivo study investigated the effects of cellulose- and gelatin-based hemostatic biomaterials on early wound healing using a murine skin wound model. Oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a porcine gelatin-based matrix (GELA) were left in situ following standardized subcutaneous implantation and compared with sham-treated controls. Tissue responses were analyzed at postoperative days 3 and 7 using histology, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR). Cellulose-based materials persisted as eosinophilic remnants, whereas fibrous matrix structures and enhanced extracellular matrix deposition were observed in the GELA group. Immunohistochemical analysis revealed increased cluster of differentiation 68 (CD68)–positive macrophage presence in the ORC group at day 3 and in the GELA group at day 7, indicating biomaterial-dependent modulation of macrophage involvement during early wound healing. Expression of Kiel 67 (Ki-67), a marker of cellular proliferation, was significantly elevated in the epidermis of the GELA group at day 7, suggesting enhanced proliferative activity during the reparative phase. In contrast, no significant differences were detected in the expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), or cluster of differentiation 14 (CD14) between groups. Overall, none of the investigated biomaterials impaired early wound healing, while the gelatin-based material demonstrated features consistent with enhanced reparative cellular responses without excessive inflammation. Full article

Background/Objectives: Severe COVID-19 is marked by IL-6-driven inflammation, endothelial injury, and dysregulated coagulation. Although IL-6 antagonists improve clinical outcomes, their effects on the temporal evolution of coagulation and fibrinolysis remain insufficiently defined. This study characterizes inflammatory, endothelial, coagulation, and fibrinolytic trajectories following IL-6 receptor blockade in critically ill COVID-19 patients. Methods: In this prospective, exploratory multicenter case series (ClinicalTrials.gov NCT05218369), 15 ICU patients with PCR- or antigen-confirmed COVID-19 received tocilizumab per protocol. Serial sampling at five timepoints (T0–T4) included routine laboratories, comprehensive viscoelastic hemostatic assays (ClotPro^®), and ELISA-based endothelial and fibrinolytic biomarkers. Analyses were primarily descriptive, emphasizing temporal patterns through boxplots; paired Wilcoxon tests with FDR correction contextualized within-patient changes. Results: Patients exhibited marked inflammation, hyperfibrinogenemia, endothelial activation, and delayed fibrinolysis at baseline. IL-6 blockade induced rapid suppression of CRP and PCT, progressive declines in fibrinogen, and modest platelet increases. In contrast, vWF antigen and activity further increased, indicating persistent endothelial dysfunction. Viscoelastic testing showed preserved thrombin generation and sustained high clot firmness, while biochemical markers (rising PAI-1, modest PAP increase, and progressively increasing D-dimer) and VHA indices suggested ongoing antifibrinolytic activity despite resolution of systemic inflammation. Conclusions: IL-6 antagonism was associated with rapid attenuation of systemic inflammation but was not accompanied by normalization of endothelial activation or fibrinolytic resistance. The observed hemostatic profile was consistent with attenuation of inflammation-associated coagulation features, while endothelial and prothrombotic alterations appeared to persist during follow-up, warranting further investigation in larger controlled studies. Full article