Blood Hemostasis Research Articles

External Bleeding and Advanced Biomacromolecules for Hemostasis.

Hemorrhage is a significant medical problem that has been an active area of research over the past few decades. The human body has a complex response to bleeding that leads to blood clot formation and hemostasis. Many biomaterials based on various biomacromolecules have been developed to either accelerate or improve the body's natural response to bleeding. This review examines the mechanisms of hemostasis, types of bleeding, and the in vitro or in vivo models and techniques used to study bleeding and hemostatic materials. It provides a detailed overview of the diverse hemostatic materials, including those that are highly absorbent, wet adhesives, and those that accelerate the biochemical cascade of blood clotting. These materials are currently marketed, under preclinical testing, or being researched. In exploring the latest advancements in hemostatic technologies, this paper highlights the potential of these materials to significantly improve bleeding control in clinical and emergency situations.

The molecular mechanisms of Caulophyllum robustum Maxim extract inhibition by regulating FAK/PI3K signaling pathway in gastric cancer HGC-27 cells

Ethnopharmacological relevanceCaulophyllumrobustum Maxim extract (CRME), as recorded in traditional Chinese medicine, has the function of dispelling Feng, regulating Qi and dredging collaterals, promoting blood circulation and regulating menstruation, gingering up and relieving pain, clearing heat simultaneously detoxifying, lowering blood pressure and hemostasis. CRME is often used as Chinese materia medica preparation for rheumatoid arthritis, traumatic injury, irregular menstruation, abdominal pain, and hypertension treatment. Since gastric cancer (GC) existed as a health problem of human over the years, we are committed to the development of potential components of Chinese herbal medicine curing cancer, and we found CRME is expected to be one of the effective anti-tumor traditional Chinese medicine preparations. Aims of the studyTo investigate the molecular mechanisms of CRME anticancer effects and the potential links between CRME and FAK. Materials and methodsCaulophyllumrobustum Maxim was extracted to obtain CRME, high-performance liquid chromatography (HPLC) was used for qualitative analysis. Information about CRME was collected from traditional Chinese medicine records and local surveys unpublished internationally. Series of cellular function experiments were applied to detect cell proliferation, migration, apoptosis, autophagy, cell cycle, angiogenesis. The xenograft model is employed in vivo. ResultsCRME can significantly inhibit HGC-27 cells on proliferation, migration and angiogenic capacity. Xenograft model indicated CRME inhibited cell proliferation in vivo. Annexin V-FITC/PI double staining assay and PI single staining assay depicted that CRME induces cell apoptosis, and arrests cell cycle at G0/G1 phase. AO (acridine orange) staining assay showed that CRME promoted autophagosome formation and inhibited autophagic flow. HPLC indicated Cauloside A and Cauloside C are components of CRME. Western blot indicated that FAK/PI3K signaling pathway is critical in the inhibition of CRME on HGC-27 cells. ConclusionsThe anti-tumor components of CRME, Cauloside A and Cauloside C, inhibited tumor progression in HGC-27 cells. This inhibition is achieved by decreasing the phosphorylation levels of FAK, thereby modulating PI3K/AKT signaling pathway.

A retrospective analysis of postpartum red blood cell transfusions at a tertiary care obstetric centre.

Postpartum anaemia is a prevalent health problem. We aimed to determine the compliance rate for red blood cell (RBC) transfusion indication among postpartum women in a single tertiary care centre in Quebec, Canada. Retrospective cohort study including all women ≥6 h postpartum who received ≥1 RBC transfusion during their delivery hospitalization between January 2005 and February 2022. We determined our centre's compliance rate by indication as compared to current society guidelines, all published after 2015 (Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis [NATA], Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG]). We then explored predictors of guideline non-compliance and described transfusion practices in our centre. A total of 171 women were included. Our centre's compliance rate was 79.5% (95% confidence interval [CI] 72.7-84.8). Predictors of guideline non-compliance were maternal medical comorbidity or abnormal placentation, both limited by large CIs (odds ratio [OR] 2.26, CI 1.02-4.94, p = 0.04; OR 4.00, CI 1.31-12.06, p = 0.01, respectively). Postpartum haemorrhage was diagnosed among 68% of the cohort, mostly due to uterine atony (73.3%). Mean baseline and nadir haemoglobin were 111 g/L (±18) and 62 g/L (±7.7), respectively. Multiple unit initial transfusion was found in a majority of patients (63.7%). Iron therapy was administered to 51.5% of women in-hospital and 81.9% received an oral iron prescription at discharge. There were no differences in primary or secondary outcomes subsequent to relevant guideline publication. Our centre's compliance rate for RBC transfusion indication meets current practice guidelines. Areas for improvement include single-unit initial transfusion protocols and adjuvant iron treatment. Antenatal optimization of haemoglobin and ferritin stores may limit postpartum transfusions.

Comparison of exsanguination and hemostasis devices for Limb surgery: a multicenter randomized controlled study

BackgroundExcessive intraoperative bleeding remains a challenge in limb surgeries. The exsanguination tourniquet ring has emerged as a potential solution for effective exsanguination and hemostasis. This study aims to evaluate its efficacy and safety compared to the conventional exsanguination and hemostasis approach (pneumatic tourniquet combined with Esmarch bandage).MethodsThis randomized controlled trial evaluates the exsanguination tourniquet ring’s effectiveness and safety versus the conventional approach in 220 participants undergoing various limb surgeries. Allocation included experimental and control groups, assesses through efficacy (including intraoperative and total blood loss, hemoglobin levels, and exsanguination and hemostasis effectiveness) and safety (adverse event occurrence) indicators.ResultsThe experimental group (n = 110) utilizes the exsanguination tourniquet ring, while the control group (n = 110) employs the conventional approach. As for intraoperative blood loss, the experimental group is non-inferior to the control group (p-value < 0.001). While no significant difference is found in total blood loss (for the full analysis set, p-value = 0.442; for the per protocol set, p-value = 0.976) and differences in postoperative and preoperative hemoglobin levels (for the full analysis set, p-value = 0.502; for the per protocol set, p-value = 0.928). Regarding exsanguination and hemostasis effectiveness, the full analysis set reveals significantly superior ratings in the experimental group compared to the control group (p-value = 0.002 < 0.05), while the per protocol set analysis indicates no significant difference between the groups (p-value = 0.504). As for safety indicators, adverse events related to the device are minimal in two groups, with only one severe event unrelated to the device.ConclusionsThe exsanguination tourniquet ring is an effective and safe device for intraoperative blood loss control in various limb surgeries.Trial registrationComparison of Exsanguination and Hemostasis Devices for Limb Surgery A Prospective Multicenter Randomized Controlled Study, ChiCTR2300077998, 11/27/2023.

A thermal cross-linking approach to developing a reinforced elastic chitosan cryogel for hemostatic management of heavy bleeding

Uncontrolled hemorrhage stands as the primary cause of potentially preventable deaths following traumatic injuries in both civilian and military populations. Addressing this critical medical need requires the development of a hemostatic material with rapid hemostatic performance and biosafety. This work describes the engineering of a chitosan-based cryogel construct using thermo-assisted cross-linking with α-ketoglutaric acid after freeze-drying. The resulting cryogel exhibited a highly interconnected macro-porous structure with low thermal conductivity, exceptional mechanical properties, and great fluid absorption capacity. Notably, assessments using rabbit whole blood in vitro, as well as rat liver volume defect and femoral artery injury models simulating severe bleeding, showed the remarkable hemostatic performance of the chitosan cryogel. Among the cryogel variants with different chitosan molecular weights, the 150 kDa one demonstrated superior hemostatic efficacy, reducing blood loss and hemostasis time by approximately 73 % and 63 % in the hepatic model, and by around 60 % and 68 %, in the femoral artery model. Additionally, comprehensive in vitro and in vivo evaluations underscored the good biocompatibility of the chitosan cryogel. Taken together, these results strongly indicate that the designed chitosan cryogel configuration holds significant potential as a safe and rapid hemostatic material for managing severe hemorrhage.

Phytochemistry and Pharmacological Activities of Panax japonicus: A Comprehensive Review

Background Panax japonicus ( P. japonicus) belongs to the Panax genus of Araliaceae and is used as medicine mainly with the bamboo whiplike rhizome, which has the functions of dispelling blood stasis and hemostasis, attenuating swelling and pain, eradicating phlegm and relieving cough, tonifying, and strength. Purpose This review intends to summarize the chemical constituents and pharmacological activities of P. japonicus to provide a scientific and systematic basis for better utilization of its rational applications. Methods The literature was searched using PubMed, Baidu Scholar and Science Hub search engines. Results The chemistry components isolated from P. japonicus are mainly saponins, besides also including polysaccharides, amino acids, volatile oils, inorganic elements, etc. P. japonicus exhibits extensive pharmacological activities including anti-inflammatory, antioxidant, lipid lowering activities, and therefore show extensive protective effects on the central nervous system, cardio-cerebrovascular system, digestive system. Conclusion This article included a thorough summary of the botany, phytochemistry, and pharmacology of P. japonicus and provided evidence for its further research and clinical applications.

Damage Control Resuscitation and Damage Control Surgery

Trauma triggers complex physiological responses with primary and secondary effects vital to understanding and managing trauma impact. "Damage Control" (DC), a concept adapted from naval practices, refers to abbreviated initial surgical care focused on controlling bleeding and contamination, critical for the survival of severely compromised patients. This impacts anaesthesia procedures and intensive care. "Damage Control Resuscitation" (DCR) is an interdisciplinary approach aimed at reducing mortality in severely injured patients, despite potentially increasing morbidity and ICU duration. Current medical guidelines incorporate DC strategies.DC is most beneficial for patients with severe physiological injury, where surgical trauma ("second hit") poses greater risks than delayed treatment. Patient assessment for DC includes evaluating injury severity, physiological reserves, and anticipated surgical and treatment strain. Inadequate intervention can worsen trauma-induced complications like coagulopathy, acidosis, hypothermia, and hypocalcaemia.DCR focuses on rapidly restoring homeostasis with minimal additional burden. It includes rapid haemostasis, controlled permissive hypotension, early blood transfusion, haemostasis optimization, and temperature normalization, tailored to individual patient needs."Damage Control Surgery" (DCS) involves phases like rapid haemostasis, contamination control, temporary wound closure, intensive stabilization, planned reoperations, and final wound closure. Each phase is crucial for managing severely injured patients, balancing immediate life-saving procedures and preparing for subsequent surgeries.Intensive care post-DCS emphasizes stabilizing patients hemodynamically, metabolically, and coagulopathically while restoring normothermia. Decision-making in trauma care is complex, involving precise patient assessment, treatment prioritization, and team coordination. The potential of AI-based decision support systems is noted for their ability to analyse patient data in real-time, aiding in decision-making through evidence-based recommendations.

Machine learning techniques for predicting microvascular network hemodynamics

Existing techniques to image microvascular networks in vivo do not allow a direct and accurate measurement of several hemodynamic variables such as the wall shear stress (WSS). They cannot also provide a full 3D characterization of blood velocity and red blood cell (RBC) concentration profiles in every vessel in a microvascular network. Such physiological parameters however play critical roles in blood flow regulation, disease progression, angiogenesis, and hemostasis. Theoretical models of network blood flow, often used for hemodynamic predictions in experimentally acquired images of the microvascular network, cannot provide the full 3D blood velocity, RBC concentration and WSS profiles as these models assume one-dimensional flow governed by Poiseuille’s law. In contrast, high-fidelity computational models that simulate flow of blood as a suspension of deformable RBCs and model the 3D vessel geometry can readily predict such physiological variables with high accuracy. Such high-fidelity computational models have recently been applied to predict hemodynamic variables in microvascular networks in silico composed of many vessels and vascular junctions. Such models, however, tend to become computationally expensive with increasing size of the network; therefore, they are not feasible for use in large networks at organ scale. To overcome this limitation, we developed a machine learning (ML) approach that can predict hemodynamic variables in 3D and with high accuracy. The ML models are based on artificial neural network and convolution-based U-net models. Using experimentally acquired images of the microvascular networks, inputs at a few inlets, and a “bank” of database that we have developed, these ML models can predict flow and RBC distribution in all vessels in the network, 3D blood velocity and RBC concentration profiles over the cross-section of every vessel, 3D WSS profiles, and time-dependent variations in blood flow in any vessel. The prediction from the ML models compare very well against the true data. Also, the prediction time using ML is significantly less than that of the high-fidelity models. The current ML models, which to our knowledge are the first of their kind, are highly promising for image-based predictions of sub-cellular resolved capillary hemodynamics in organ-scale networks. This study paves the way for AI to make hemodynamic predictions in organ-scale capillary vessel networks while retaining the sub-cellular scale details and overcoming the limitations of the in vivo imaging techniques, with potential applications in hematological and microvascular disorders, angiogenesis, and vascular-mediated drug delivery. Funded by NIH (R01-EY033003) and NSF (CBET 2302212). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Korelasi Jumlah Trombosit dengan Kadar Albumin pada Penderita Demam Berdarah Dengue (DBD) di Kota Mataram

Dengue Hemorrhagic Fever (DHF) is a disease caused by the dengue virus. DHF can cause two main pathological changes, namely increased capillary permeability, which causes hemoconcentration due to a decrease in plasma volume in the blood vessels and hemostasis disorders caused by coagulopathy, vasculopathy and thrombocytopenia. Routine examination parameters for dengue sufferers are complete blood to monitor platelet counts. Supporting examinations are also required, one of which is checking albumin levels. This research aims to know of determine the correlation between platelet counts and levels in dengue fever sufferers in Mataram City. This research uses the Observational Analytical method with a cross sectional approach. DHF sufferers will have a complete blood count and albumin examination, then an analysis will be carried out using the Spearman test. This study used 24 samples and it was found that the overall average platelet count was 56,000/ul of blood. The platelet value was obtained with a range of 26,000/ul blood to 91,000/ul blood. The overall average albumin level is 3.28 g/dL, with a range of albumin levels from 2.78 g/dL to 4.12 g/dL. There is a relationship between platelet count and albumin levels in dengue fever sufferers in Mataram City based on the results of the Spearman test with a p value &lt;0.05.

Wound microenvironment-responsive peptide hydrogel with multifunctionalities for accelerating wound healing.

The fabrication of wound microenvironment-responsive peptide hydrogels with hemostatic ability, antibacterial activity, and wound healing potential remains a challenge. Herein, we constructed a multifunctional dressing by inducing the self-assembly of a peptide (Pep-1) and water-soluble new methylene blue (NMB) through electrostatic interaction. The self-assembly mechanism was demonstrated using a combination of transmission electron microscopy, circular dichroism spectrum, fluorescence spectrum, Zeta potential, and rheological analysis. The Pep-1/NMB hydrogel also exhibited a faster drug release rate in wound acidic environment. Furthermore, when Pep-1/NMB was exposed to a 635 nm laser, its antibacterial ratios increased sharply to 95.3%, indicating remarkably improved antibacterial effects. The findings from the blood coagulation and hemostasis assay indicated that Pep-1/NMB effectively enhanced the speed of blood clotting in vitro and efficiently controlled hemorrhage in a mouse liver hemorrhage model. Meanwhile, hemolytic and cytotoxicity evaluation revealed that the hydrogel had excellent hemocompatibility and cytocompatibility. Finally, the findings from the wound healing studies and H&E staining indicated that the Pep-1/NMB hydrogel had a significant impact on cell migration and wound repair. The results indicated that wound microenvironment-responsive Pep-1/NMB hydrogel had significant potential as a highly effective wound dressing platform, offering rapid hemostasis, antibacterial, and wound healing acceleration properties.

Hematological And Hemostasis Profile, Thrombotic Risk In Sickle Cell Patient In Cameroon : An Analytical Cross-Sectional Study

Background : Thrombosis is a disease characterized by the formation of blood clots inside the vessels. It is a situation commonly encountered during certain pathologies in general and sickle cell disease in particular during which it is associated with a very high risk of ischemic stroke. The purpose of this study is to determine the profile of blood count and thrombotic risk in sickle cell patients. Methodology : We conducted an analytical cross-sectional study at the Bafoussam Regional Hospital over 03 months. The study population consisted of consecutively recruited homozygous sickle cell and sickle cell traits. Blood samples from the latter were collected and sent to the laboratory for the completion of the blood count and hemostasis profile. The results obtained were analyzed using statistical software R version 4.1.1. Univariate logistic regression analyses were used to identify factors associated with thrombotic risk in our study population. Results : The size of our population was 148 patients including 80 sickle cell patients and 68 with sickle cell trait AS. The frequency of thrombotic risk in the population was 35.1% with 52,5% in SS and 14.7%% in AS (p=0.002). The mean fibrinogen in SS and AS was 5.32±0.50 g/L and 4.63±0.00 g/L respectively (p&lt;0.001). The mean Quick Time was 11.8±1.94 s for SS and 12.2±2.72 s for AS (p=0.336). The mean cephalin time and activator were 23.3±5.90 s for SS and 24.3±7.89 s for AS with and (p=0.395), respectively. The mean D-dimer in SS was 1.88±2.09 mg/L and 1.12±2.40 mg/L in AS (p=0.045). The mean hemoglobin in SS was 7.13±1.41 g/dL and in AS was 14.4±2.57 g/dL (p&lt;0.001). Thrombocytosis is positively associated with thrombotic risk (Or = 2.52, 95% CI = [1.13; 5.63] ; (p=0.022)). Moreover, ‘AS’ status is beneficial for the occurrence of thrombotic risk unlike SS (Or = 0.16, 95% CI = [0.07; 0.35]; (p=0.001). In addition, elevated fibrinogen is a risk factor for thrombotic risk (OR=2.50, 95% CI = [4.99; 1.25]; p=0.009). Conclusion : Given the weight of sickle cell disease and its complex pathophysiology, knowledge, and understanding of thrombotic risk is imperative to guide therapeutic strategies in the management and clinical management of patients. These data highlight the need for regular and systematic hemostasis assessment in sickle cell patients to prevent possible risks of thrombosis.

Predicting capillary vessel network hemodynamics in silico by machine learning.

Blood velocity and red blood cell (RBC) distribution profiles in a capillary vessel cross-section in the microcirculation are generally complex and do not follow Poiseuille's parabolic or uniform pattern. Existing imaging techniques used to map large microvascular networks in vivo do not allow a direct measurement of full 3D velocity and RBC concentration profiles, although such information is needed for accurate evaluation of the physiological variables, such as the wall shear stress (WSS) and near-wall cell-free layer (CFL), that play critical roles in blood flow regulation, disease progression, angiogenesis, and hemostasis. Theoretical network flow models, often used for hemodynamic predictions in experimentally acquired images of the microvascular network, cannot provide the full 3D profiles either. In contrast, such information can be readily obtained from high-fidelity computational models that treat blood as a suspension of deformable RBCs. These models, however, are computationally expensive and not feasible for extension to the microvascular network at large spatial scales up to an organ level. To overcome such limitations, here we present machine learning (ML) models that bypass such expensive computations but provide highly accurate and full 3D profiles of the blood velocity, RBC concentration, WSS, and CFL in every vessel in the microvascular network. The ML models, which are based on artificial neural networks and convolution-based U-net models, predict hemodynamic quantities that compare very well against the true data but reduce the prediction time by several orders. This study therefore paves the way for ML to make detailed and accurate hemodynamic predictions in spatially large microvascular networks at an organ-scale.

Features of the systemic influence of cervical cancer on peripheral blood and hemostasis according to the tumor histological subtype

Aim. To identify the features of the systemic effect on hematopoiesis and the blood coagulation system of different histological subtypes of cervical cancer (CC).Materials and methods. A single-center retrospective cohort study of 428 patients (61 patients with high grade squamous intraepithelial lesion (carcinoma in situ) and 367 patients with CC) examined from 1997 to 2022 in the Polyclinic of P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia. The age of patients was from 18 to 90 years (median age – 42 [34; 51] years). Patients were divided into 4 groups: group 1 – patients with high grade squamous intraepithelial lesion and 3 groups depending on tumor’s histological subtype (squamous cell, glandular squamous cell, adenocarcinoma). Demographic and clinical data were analyzed including laboratory tests (general blood count, biochemical blood test and iron metabolism and coagulograms (total 32 variables)) compared to clinical and surgical stages of CC.Results. High grade squamous intraepithelial lesion does not have a systemic effect on the parameters of general, biochemical blood tests and hemostasis (p &gt;0.05). On the other hand, statistically significant changes were found in the parameters of routine laboratory blood tests, which correlate with the results of microinvasive analysis of CC, thus revealing the systemic effect of a malignant tumor: at p ≤0.001 for thrombin time, total protein, alkaline phosphatase levels; at p ≤0.05 for alanine aminotransferase, aspartate aminotransferase, C-reactive protein, serum iron and urea levels. Among patients with CC, statistically significant (p&lt;0.001) correlations were obtained between hematological, hemostasiological and biochemical blood parameters. Of statistical significance, the presence of the glandular component in the tumor increases the systemic effect of CC on blood parameters, hemostasis, markers of inflammation and iron metabolism: leukocytosis and maximum erythrocyte sedimentation rate values compared to CC, high fibrinogen and the level of soluble fibrin-monomer complexes which increased activation of coagulation hemostasis along the common coagulation pathway (thrombin time) (p&lt;0.001). It leads to an increase in the risk of venous thromboembolic complications in this category of patients.Conclusion. The identified changes in blood parameters made it possible to reveal the unique biological characteristics of each histological subtype of CC, including biochemical ones, which will help in developing an improved diagnosis of CC depending on the histological subtype and stage of the disease, along with developing preventive measures and treatment methods adapted to each specific case.

Based on In Vitro and 3D Epidermal Skin Model: The Efficacy of Bletilla Striata Extract for Skin Care

Introduction: Bletilla Striata (Thunb. ex A. Murray) Rchb. f.) Is a native herb of the orchidaceae family. Modern pharmacological activity studies have shown that Bletilla striata mainly has pharmacological activities such as promoting blood circulation and hemostasis, promoting wound healing anticancer, anti-tumor disease-resistant pathogenic microorganisms, protecting mucosa, anti-ulcer, whitening and anti-oxygen, anti-aging, and immune regulation, which have been widely recognized and applied. Research on the efficacy of plant extracts mainly adopts in vitro testing methods, such as cell experiment and 3D skin model experiment. Objective: To evaluate the soothing effect of Bletilla striata extracton UVB-stimulated keratinocytes (HaCaT) and its barrier repair efficacy in Skinovo-Epi skin model. Methods: The soothing and barrier repairing effects of Bletilla striata extract were studied in vitro. The cytotoxicity of the sample was measured by MTT assay, and cytotoxicity to keratinocytes was evaluated by cell survival rate. The soothing effect was evaluated by detecting changes in inflammatory cytokines (IL-6, IL-1β, IL-8, TNF-α) secreted by UVB-stimulated keratinocytes with the sample treatment. Barrier repair efficacy was assessed in a Skinovo-Epi skin model by measuring changes in FLG (Filaggrin) and LOR (Loricrin) protein levels after topical application of the sample. Results: The sample showed low cytotoxicity on keratinocytes. The sample significantly reduced UVB-stimulated secretion of inflammatory cytokines in keratinocytes. Topical application of the sample increased FLG and LOR protein levels in the Skinovo-Epi skin model. Conclusions:Bletilla striata extract exhibits soothing and barrier repair activities in vitro. Bletilla striata extract reduces UVB-stimulated inflammation in keratinocytes and improves skin barrier function. The data provide novel experimental evidence supporting the innovative application of Bletilla striata for skin disorders. Bletilla striata has potential as a therapeutic herb for sensitive and damaged skin conditions.

Correlation between blood rheology, hemostasis and functional status in patients with chronic heart failure: rationale and study protocol

Correlation between blood rheology, hemostasis and functional status in patients with chronic heart failure: rationale and study protocol

Developmental adcyap1b loss leads to hemorrhage, disrupted hemostasis, and a blood coagulation cascade in zebrafish

BackgroundPituitary adenylate cyclase–activating polypeptide is a neuropeptide with diverse roles in biological processes. Its involvement in the blood coagulation cascade is unclear. ObjectivesThis study unraveled adcyap1b’s role in blood coagulation using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 in zebrafish. Effects were validated via adcyap1b knockdown. Gene expression changes in adcyap1b mutants were explored, linking them to clotting disorders. An analysis of proca gene splicing illuminated its role in adcyap1b-related anticoagulation deficiencies. MethodsZebrafish were genetically modified using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 to induce adcyap1b knockout. Morpholino-mediated gene knockdown was employed for validation. Expression levels of coagulation factors, anticoagulant proteins, and fibrinolytic system genes were assessed in adcyap1b mutant zebrafish. Alternative splicing of proca gene was analyzed. ResultsAdcyap1b mutant zebrafish exhibited severe hemorrhage, clotting disorders, and disrupted blood coagulation. Morpholino-mediated knockdown replicated observed phenotypes. Downregulation in transcripts related to coagulation factors V and IX, anticoagulation protein C, and plasminogen was observed. Abnormal alternative splicing of the proca gene was identified, providing a mechanistic explanation for anticoagulation system deficiencies. ConclusionAdcyap1b plays a crucial role in maintaining zebrafish blood coagulation and hemostasis. Its influence extends to the regulation of procoagulant and anticoagulant pathways, with abnormal alternative splicing contributing to observed deficiencies. These findings unveil a novel aspect of adcyap1b function, offering potential insights into similar processes in mammalian systems.

Manipulating mechanical properties of PEG-based hydrogel nanocomposite: A potential versatile bio-adhesive for the suture-less repair of tissue

Multifunctional bio-adhesives with tunable mechanical properties are obtained by controlling the orientation of anisotropic particles in a blend of fast-curing hydrogel with an imposed capillary flow. The suspensions' microstructural evolution was monitored by the small-angle light scattering (SALS) method during flow up to the critical Péclet number (Pe≈1) necessary for particle orientation and hydrogel crosslinking. The multifunctional bio-adhesives were obtained by combining flow and UV light exposure for rapid photo-curing of PEGDA medium and freezing titania rods' ordered microstructures. Blending the low- and high-molecular weight of PEGDA polymer improved the mechanical properties of the final hydrogel. All the hydrogel samples were non-cytotoxic up to 72 h after cell culturing. The system shows rapid blood hemostasis and promotes adhesive and cohesive strength matching targeted tissue properties with an applicating methodology compatible with surgical conditions. The developed SALS approach to optimize nanoparticles’ microstructures in bio-adhesive applies to virtually any optically transparent nanocomposite and any type of anisotropic nanoparticles. As such, this method enables rational design of bio-adhesives with enhanced anisotropic mechanical properties which can be tailored to potentially any type of tissue.

Type-O Blood Is Not Associated With Elevated Mortality After Trauma: A North American Cohort Study.

Recent studies have presented contradictory findings on the relationship between blood type and mortality in trauma patients. Using the largest population in a study of this type to date, we hypothesized that ABO genotype and Rhesus status would influence trauma-related mortality and morbidity given the relationship between blood type and hemostasis. Data from all trauma patients admitted to level I and level II trauma centers in one city over a five-year period was retrospectively analyzed. Patients were stratified by ABO type. Patient demographics and outcomes were then assessed. Chi-squared and Fisher's exact tests were used to analyze categorical variables. Continuous variables were analyzed using ANOVA or Kruskal-Wallis tests as appropriate. Logistic regression was used to determine independent associations for 28-day mortality and complications. Of 5249 patients, severe injury (ISS >15) was present in 1469. Approximately one-quarter of patients with severe injury received blood products within the first 24 hours. There were no significant variations in demographics or complications between patients of different blood types. Univariate and multivariable regression analysis showed no association between blood type and mortality. However, penetrating injury, lower GCS, higher ISS, blood transfusion within 24 hours, and Asian descent were associated with higher overall mortality. In contrast to previous studies, we found no evidence of an association between blood type and mortality. However, our findings suggest that patients of Asian descent may be at higher risk for mortality following trauma. Further research is warranted to explore this observation.

Screening and verification of hemostatic effective components group of Panax Notoginseng based on spectrum-effect relationships

Ethnopharmacological relevancePanax Notoginseng (PN) can disperse blood stasis, hemostasis, and detumescence analgesic, which can be used for hemoptysis, hematemesis and another traumatic bleeding, and it is known as “A miracle hemostatic medicine”. Studies show that the chemical composition of PN is relatively comprehensive, however, its hemostatic active ingredients have not been fully clarified. Aim of studyThis study aimed to clarify the hemostatic effective components group (HECG) of PN, provide a foundation for the assessment of PN's quality and its comprehensive development, and for further studies on the pharmacodynamic material basis of other Traditional Chinese Medicines (TCMs). Materials and methodsUPLC-MS was used to establish the fingerprint and identify the common peaks in 44 batches of PN extracts (PNE). In addition, the plasma recalcification time and in vitro coagulation time were measured. For spectrum-effect analysis, bivariate correlation analysis (BCA) and partial least squares regression analysis (PLSR) were used to screen the hemostasis candidate active monomers of PN. The monomers were prepared by combining several preparative chromatography techniques. The efficacy was verified by plasma recalcification time, in vitro coagulation time, and a rat model of gastric hemorrhage. ResultsA total of 30 common peaks and hemostatic efficacy indexes of 44 batches of PNE were obtained. A total of 18 components were positively correlated with the comprehensive coagulation index by two statistical methods. Six and eleven monomers were obtained respectively by chromatographic preparation and procurement, and one monomer was eliminated due to preparation difficulty and other reasons. Seven active monomers with direct hemostatic effect and one active monomer with synergistic hemostatic effect were screened through plasma recalcification time, and their combinations were used as candidate HECG for hemostatic effect verification. The results of in vitro experiments showed that plasma recalcification time and in vitro coagulation time were significantly reduced (P < 0.05) in the HECG group, compared to the PNE group. The results of in vivo experiment also indicated that the hemostatic effect of HECG was comparable to that of PNE and PN powder. ConclusionThe composition and efficacy of the HECG of PN were screened and verified using the spectral correlation method and in vivo and in vitro efficacy verification; the HECG included Dencichine, Ginsenoside Rg1, Ginsenoside Rd, Ginsenoside Rh1, Ginsenoside F1, Notoginsenoside R1, Notoginsenoside Ft1 and Notoginsenoside Fe. These results laid a foundation for the quality evaluation of PN and provided a reference for the basic research of pharmacodynamic material basis of other TCMs.

Hemostatic activity &lt;i&gt;in vitro&lt;/i&gt; of lectin-containing substances of bryathypes on the example of some Antarctic and Belarus representatives

BACKGROUND: The modern market of medical devices in Belarus and Russia is represented by a wide range of hemostatic agents, of which the most popular are local hemostatics of plant origin possessing the significant technological potential for renewal and improvement. A promising reserve for this may be biologically active compounds of mosses, which are characterized by anti-inflammatory, antibacterial and antifungal effects. However, their hemostatic effect is almost not studied, which determines the relevance of this work. AIM: The aim of this work is to study the effect of lectin-containing substances from mosses of three species collected in East Antarctica and Belarus on the parameters of human blood hemostasis in vitro. MATERIALS AND METHODS: We studied mosses of the genera Bryum, Ceratodon, and Coscinodon, collected in the area of the Belarusian Antarctic station Gora Vechernyaya in East Antarctica and in Belarus. Lectin-containing substances of mosses were obtained by extracting shoots in 0.05 M tris-HCl buffer (pH 8.0), centrifugation, filtration. The assessment of the biological activity of lectin-containing substances in mosses was carried out by the agglutination reaction of rabbit erythrocytes, as well as the effect on human platelet aggregation and in the test for activated partial thromboplastin time. RESULTS: It was established that lectin-containing substances of the studied moss species had agglutinating activity against erythrocytes in the range from 11708.28 (Belarusian samples) to 1333979.59 U/mg of protein (Antarctic samples) depending on the species and localization; initiated the aggregation of human platelets (25–80% of the effect of thrombin) regardless of blood group, Rh and gender of donors; influenced the plasma link of hemostasis, reducing activated partial thromboplastin time (by 15–18%). CONCLUSIONS: It was found that some species of mosses of the genera Bryum, Ceratodon and Coscinodon of Antarctica and Belarus had an agglutinating and hemostatic effect on erythrocytes and platelets, with the greatest activity noted for Antarctic species. A hypothesis has been put forward that the observed phenomenon is due to the structural features of proteins, including lectins. It is assumed that lectins are possible inducers of erythrocyte agglutination and platelet aggregation in mosses. It is shown that the moss species Bryum pseudotriquetrum and Ceratodon purpureus have a certain resource potential in Belarus for their annual harvest. The results obtained expand the list of moss species with hemostatic activity, and can be used to develop new hemostatics of plant origin for local use from Belarusian plant materials.