Blood Coagulation Process Research Articles

Bleeding time and clotting time post-extraction Rattus norvegicus tooth treated with ethanol extract gel from Terminalia cattapa L. leaves

Link of Video Abstract: https://youtu.be/iJSDiYl-BmA Introduction: Post-extraction bleeding is a complication that is often encountered in dental practice. A decrease in the number of platelets will increase the risk of bleeding. If left untreated, complications can range from hematoma to severe blood loss. The use of medicinal plants is common in traditional medicine throughout the world. Flavonoids and tannins are the main compounds that play a role in the blood clotting process. The ethanol extract of Terminalia catappa L. leaves contains: saponins, alkaloids, tannins, flavonoids, triterpenoids, and phenols. This research aims to determine bleeding time and clotting time after tooth extraction. White mice were given ethanol extract gel from Terminalia cattapa L. leaves. Method: Study design using randomized with post-test only control group design, in vivo. A population of 35 male white rats (Rattus norvegicus) of the Wistar strain, were grouped randomly into 7 groups. The extraction of white rat teeth using artery clamps, measurement of bleeding time and clotting time using three stopwatches, and the results were averaged. Result: The results of the research showed that the ethanol extract gel of Terminalia cattapa L. leaves had a shorter bleeding time and clotting time than pure gel, after tooth extraction from white rats. Conclusion: Terminalia catappa L. leaf ethanol extract gels have the ability to shorten bleeding time and clotting time and the best gel concentration is 50%.

The role of neutrophil extracellular traps in thrombosis

According to the cellular model of hemostasis, the process of blood coagulation is presented in the form of three phases: initiation, amplification and propagation, each of them includes several consecutive stages. At the same time, thrombus formation is often explained by Virchow’s triad: blood stasis, damage to the blood vessel walls, and hypercoagulation. Classically, the appearance of one of the three mentioned parameters can lead to thrombus formation. Over the past decade, our knowledge of the cross-talk between coagulation, inflammation, and innate immune activation and the involvement of neutrophil extracellular traps in these processes has expanded. This brief review shows their role in thrombosis through the mechanisms of activation of platelets, complement, interaction with blood coagulation factors and damage to the vascular endothelium. We searched the literature in the MEDLINE database on the PubMed platform.

Investigation of thrombogenic risk factors in young adult male sportsmen

Abstract The study aimed to check the impact of sportsmen’s physical activity on blood coagulation processes and myocardial micro injuries in young adult male sportsmen. Comparing the results of athletes before and after 6 months of the training season, a statistically significant increase in the following parameters: PT (12.03±0.76 vs. 13.51±0.72 s; p<0.01), INR (1.03±0.07 vs. 1.14±0.06; p<0.01), APPT (28.73±3.27 vs. 33.31±5.63 s; p<0.01) and TT (20.62±0.97 vs. 22.49 ±1.41 s; p<0.01) was observed. Analyzing the results between the control group and the study group before training, the following changes were observed: APTT (35.26±6.74 vs. 28.73±3.27 s; p<0.01), HGMCR (750.17±59.23 vs. 569.38±51.24 ng/L; p <0.01) and L-FABP (329.16±92.04 vs. 151.80±70.10 ng/L; p=0.02) and an increase in H-FABP level (2.75±1.32 vs. 4.14±1.30 ng/mL; p<0.01). Comparing the values between the control group and the study group, but after training, an increase in the value for PT (12.88±1.41 vs. 13.51±0.72 s; p = 0.02), INR (1.09±0.13 vs. 1.14±0.06; p=0.02), TT (20.64±1.43 vs. 22.49±1.41 s; p<0.01) and H-FABP (2.75±1.32 vs. 3.94±1.47 ng/L; p<0.01) and decrease in HGMCR activity (750.17±59.23 vs. 581.47±51.25 ng/L; p<0.01) were observed. There was also a strong positive correlation between HGMCR and H-FABP (r = 0.77) and a strong negative correlation between TT and Fb (r = -0.808) and between TT and APTT (r = -0.424). Summarizing our study, we confirm that physical activity in sportsmen, especially overtraining, may have an impact on blood coagulation processes and may also lead to microdamage of the heart muscle.

Identification of Genetic Loci That Modify the Scarb1 and Apoe Atherothrombotic Phenotype

Introduction: Atherothrombosis, or the formation of a thrombus on a ruptured atherosclerotic plaque, is a major health problem in western societies and can lead to myocardial infarction and ischemic stroke. Atherosclerotic plaques form on the inner walls of blood vessels and consist of macrophages, lipids, and prothrombotic molecules such as tissue factor that initiate the blood clotting process. Despite the complexity of atherothrombotic disease, with major (and evolving) environmental contributors, genetic variants play a role in modifying the disease process. In mice, deficiency of the Scavenger Receptor Class B type 1 (Scarb1) and Apolipoprotein E (ApoE) genes play important roles in the proper maintenance of lipid levels in the body. The Scarb1 protein is an HDL receptor known for its role in the process of transporting cholesterol from peripheral tissues toward the liver for excretion. The ApoE protein combines with lipids to form lipoproteins that package cholesterol and carry it throughout the circulation. In order to study mice deficient in these proteins, our lab produced Scarb1 and ApoE double knockout (dKO) mice on the C57BL/6J (B6) and 129S1/SvImJ (129S1) background and discovered major phenotypic differences in size and survival. Mice with a mixed 129S1/B6 background succumb to lethal atherothrombosis at approximately 8 weeks of age (as seen in Figure 1), whereas dKOs generated on the B6 background die at approximately 5 days old. We hypothesized that specific 129S1 genetic variants modify the severity of atherothrombosis in dKO mice. Methods: We produced F1-F3 generation dKO mice on the mixed 129S1/B6 background for experiments. Weights were taken for the 38 dKO mice and their littermates from 3 weeks old until the death of the knockout mice at around 8 weeks of age. Purified DNA from the dKO mice was subjected to whole genome genotyping for 143,000 markers using the GigaMUGA genotyping platform (Neogen). Weight data were used as a phenotype to perform quantitative trait loci analysis (QTL) to identify potential loci responsible for the phenotypic weight differences. Results: dKO mice from F1-F3 generations were born at the expected Mendelian frequencies but exhibited 3 distinct phenotypes based on their weights relative to their littermates. dKO mouse weights fell into 3 distinct categories: (1) indistinguishable from littermates, (2) 14%-39% less than littermates, (3) greater than 39% less than littermates. QTL analysis identified 6 loci above the significance threshold of 4.04 on Chromosomes (Chr) 1 (LOD 6.82), 2 (LOD 6.44) , 3 (LOD 4.65), 6 (LOD 4.30), 12 (LOD 4.22) and 14 (LOD 5.36; Figure 2). In addition, interaction analyses identified significant interactions of Chr 12 with Chrs 1, 2, 3, and 14. The Chr 12 candidate region is between 83 and 93 Mb consisting of 89 genes. Niemann Pick type C2 ( Npc2), an intracellular cholesterol transporter, is within the candidate region. Thus, 129S1 variants in this region affecting Npc2 transcription are strong candidates for modifying the dKO phenotypes. Discussion: We have analyzed 38 dKO mice for genetic variants affecting their health, as measured by weights relative to their non dKO littermates. We identified 6 significant genetic loci, with Npc2 as a candidate gene for the Chromosome 12 locus. Studies to reinforce these findings include the analysis of an additional cohort of dKO mice to narrow the candidate QTL intervals, analysis of Npc2 expression in the B6 and 129 strain, histology of the liver to visualize lipid accumulation, blood smears to examine the blood cell size difference in dKOs, and sequencing with GigaMUGA. The identification of atherothrombosis modifier genes could result in novel treatment strategies for atherothrombosis.

Unveiling the Potent Fibrino(geno)lytic, Anticoagulant, and Antithrombotic Effects of Papain, a Cysteine Protease from Carica papaya Latex Using κ-Carrageenan Rat Tail Thrombosis Model

While fibrinolytic enzymes and thrombolytic agents offer assistance in treating cardiovascular diseases, the existing options are associated with a range of adverse effects. In our previous research, we successfully identified ficin, a naturally occurring cysteine protease that possesses unique fibrin and fibrinogenolytic enzymes, making it suitable for both preventing and treating cardiovascular disorders linked to thrombosis. Papain is a prominent cysteine protease derived from the latex of Carica papaya. The potential role of papain in preventing fibrino(geno)lytic, anticoagulant, and antithrombotic activities has not yet been investigated. Therefore, we examined how papain influences fibrinogen and the process of blood coagulation. Papain is highly stable at pH 4–11 and 37–60 °C via azocasein assay. In addition, SDS gel separation electrophoresis, zymography, and fibrin plate assays were used to determine fibrinogen and fibrinolysis activity. Papain has a molecular weight of around 37 kDa, and is highly effective in degrading fibrin, with a molecular weight of over 75 kDa. Furthermore, papain-based hemostatic performance was confirmed in blood coagulation tests, a blood clot lysis assay, and a κ-carrageenan rat tail thrombosis model, highlighting its strong efficacy in blood coagulation. Papain shows dose-dependent blood clot lysis activity, cleaves fibrinogen chains of Aα, Bβ, and γ-bands, and significantly extends prothrombin time (PT) and activated partial thromboplastin time (aPTT). Moreover, the mean length of the infarcted regions in the tails of Sprague–Dawley rats with κ-carrageenan was shorter in rats administered 10 U/kg of papain than in streptokinase-treated rats. Thus, papain, a cysteine protease, has distinct fibrin and fibrinogenolytic properties, suggesting its potential for preventing or treating cardiovascular issues and thrombosis-related diseases.

Multichannel resonant acoustic rheometry system for quantification of coagulation of multiple human plasma samples

Resonant Acoustic Rheometry (RAR), a newly developed ultrasound-based technique for non-contact characterization of soft viscoelastic materials, has shown promise for quantitative viscoelastic assessment of temporally changing soft biomaterials in real time, and may be used to monitor blood coagulation process. Here, we report the development of a novel, multichannel RAR (mRAR) system for simultaneous measurements of multiple temporally evolving samples and demonstration of its use for monitoring the coagulation of multiple small-volume plasma samples. The mRAR system was constructed using an array of 4 custom-designed ultrasound transducers at 5.0 MHz and a novel electronic driving system that controlled the generation of synchronized ultrasound pulses for real time assessment of multiple samples simultaneously. As a proof-of-concept of the operation of the mRAR system, we performed tests using pooled normal human plasma samples and anti-coagulated plasma samples from patients treated with warfarin with a range of International Normalized Ratio (INR) values as well-characterized samples with different coagulation kinetics. Our results show that simultaneous tracking of dynamic changes in 4 plasma samples triggered by either kaolin or tissue factor was achieved for the entire duration of coagulation. The mRAR system captured distinct changes in the samples and identified parameters including the clotting start time and parameters associated with the stiffness of the final clots that were consistent with INR levels. Data from this study demonstrate the feasibility of the mRAR system for efficient characterization of the kinetic coagulation processes of multiple plasma samples.

Assessment of plasma hemostasis system in the early postoperative period in patients after abdominoplasty

Introduction Venous thromboembolic complications after abdominoplasty are associated with increased intraabdominal pressure and altered venous return without taking into account possible changes in the activity of the blood coagulation system.Purpose of work was to evaluate the state of the plasma hemostasis system in the early postoperative period in patients after abdominoplasty.Materials and methods The study included 100 patients who underwent aesthetic abdominoplasty. Prothrombin (PT), fibrinogen (FG), activated partial thromboplastin time (APTT), soluble fibrin-monomer complexes (SFMC), euglobulin clot lysis (ECL), antithrombin-III (AT-III), and protein C (PrC) levels were evaluated before surgery, immediately after surgery, on the first, third and fifth days after surgery. Statistical data analysis was performed using SPSS 16, Excel 2010 for Windows, using the Kruskal – Wallis criterion.Results Coagulation hemostasis was characterized by a decrease in PT immediately after the surgery and on the first day by 13.9 and 5.3, and an increase in PT on the third and fifth days by 12.3 and 15.5 (p < 0.001), decrease in FG on the first, third and fifth days by 0.49 g/L, 2.34 g/L, and 2.04 g/L, respectively (p < 0.001). SFMC increased at all postoperative stages by 4.7, 8.2, 10.8, and 10.0 times (p < 0.001). Inhibition of XII-dependent fibrinolysis was characterized by an increase in ECL time on the first, third and fifth days by 2.8, 9.7, and 6.3 minutes, respectively (p < 0.001). AT-III and PrC levels decreased immediately after the surgery by 18.8 and 8.9, on the first day by 14.2 and 11.2, and on the third day by 8.8 and 6.3 respectively (p < 0.001).Discussion Activation of blood coagulation processes with imbalance of coagulation, anticoagulation, and fibrinolytic systems create conditions for venous thrombosis formation after abdominoplasty, which substantiates the necessity of VTE pharmacoloprophylaxis for at least five days.Conclusion In the early postoperative period abdominoplasty is accompanied by activation of plasma coagulation, inhibition of fibrinolytic system activity and reduction of natural anticoagulant activity.

Biomimetic Hemostatic Powder Derived from Coacervate-Immobilized Thermogelling Copolymers.

Intrinsic hemostasis is an innate body response to prevent bleeding based on the sol-gel transition of blood. However, it is often inadequate for exceptional situations, such as acute injury and coagulation disorders, which typically require immediate medical intervention. Herein, we report the preparation of an efficient hemostatic powder, composed of tannic acid (TA), poly(ethylene glycol) (PEG), and poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) triblock copolymer (TB), for biomimetic hemostasis at the bleeding sites. TA has a high affinity for biomolecules and cells and can form coacervates with PEG driven by hydrogen bonding. TB enhances the mechanical strength and provides thermoresponsiveness. The hemostatic powder can rapidly transit into a physical and biodegradable seal on wet substrates under physiological conditions, demonstrating its promise for the generation of instant artificial clots. Importantly, this process is independent of the innate blood clotting process, which could benefit those with blood clotting disorders. This biomimetic hemostatic powder is an adaptive topical sealing agent for noncompressible and irregular wounds, which is promising for biomedical applications.

Physical-chemical repurposing of drugs. History of its formation in Russia

It is reported that the traditional scheme of finding and developing a new drug and conducting the whole complex of preclinical studies requires several thousand chemical compounds, hundreds of millions of US dollars and more than 12 years of work. It is shown that physicochemical pharmacology was born in Russia at the end of the 20th century, which in our days has been transformed into physicochemical repurposing of known medicines. The first successfully repurposed known drug was a solution of 4% potassium chloride, which had previously traditionally belonged to the group of macro- and microelements, used by intravenous injections to regulate acid-base balance and rhythmic activity of the heart. In 1983, it was stated that this medicinal solution, when heated to 3942C and applied topically by irrigation of the bleeding surface, could be classified as a vasoconstrictor and hemostatic drug. Hyperthermia was used as a physico-chemical reprofiling factor, which, according to the Arrhenius law, accelerated and intensified, on the one hand, the spastic action of K+ cations on the gaping blood vessels (formation of hyperkalium contracture in the smooth muscles of the vascular wall) and, on the other hand, the blood clotting process in the wound. In subsequent years, the promise of physicochemical repurposing of known drugs was shown on the example of water, hydrogen peroxide, sodium chloride and sodium bicarbonate by purposefully changing their temperature, acid, osmotic activity, as well as the amount and quality of gas content (passing). A chronology of the physicochemical repurposing of known drug solutions and tablets is described and the essence of such new groups of drugs as bleachers of bruises and pyolytics is given. It is shown that both groups of drugs were discovered in Russia and are intended for local use to bleach bruises (blood stains) and dissolve thick mucus, sputum, pus, blood clots, meconium and other dense biological tissues containing the enzyme catalase. It is pointed out that the advantage and at the same time the limitation of the known drugs repurposed according to this scheme is their local application, since their new pharmacological activity is caused mainly by the physical and chemical principle of action, which is manifested by local interaction with the selected area of the patients organism.

Protein S Defficiency and The Mechanism of Protein S in Hemostasis and Atherosclerosis

Protein S (PS) is Vitamin K dependant protein which plays a role in regulating the blood clotting process in the body. Protein S deficiency is explained as a condition characterized by reduced levels of protein S in the serum so that it makes the blood clot too easily. The purpose of this literature review is to give an update of protein S defficiency and the mechanism of protein s in hemostasis and atherosclerosis based on publish literature reference from various database. Protein S plays important role in hemostasis by regulating blood cloth process in the initiation phase of the extrinsic pathway as a TFPI cofactor or in the propagation phase, namely as an APC cofactor and independent activity of TFPIα and APC. Protein S deficiency is known to be associated with the occurrence of atherosclerosis via the Tyro3-Axl-Mer (TAM) receptor. The main clinical manifestations of the majority of patients with heterozygous mutations in the protein S (PROS1) gene are deep vein thrombosis (DVT) and pulmonary embolism that precipitate by VTE. Administration of anticoagulant drugs such as heparin in the form of low-molecular-weight heparin (LMWH) or unfractionated heparin, vitamin K antagonists (VKA), namely warfarin, or direct oral anticoagulants (DOACs) can be selected as a management of protein S deficiency with VTE. Protein S has a central role in the coagulation prosses and its deficiency associated with atherosclerotic conditions.

Bombyx batryticatus extract activates coagulation factor Ⅻ to promote angiogenesis in rats with cerebral ischemia/reperfusion injury

Ethnopharmacological relevanceBombyx batryticatus is traditionally used to treat patients with stroke, but its mechanism remains unclear. Aim of the studyTo explore the interventional effect of Bombyx batryticatus extract as an activator of FⅫ on angiogenesis of rats with cerebral ischemia/reperfusion injury. Materials and methodsFirstly, the mechanism of Bombyx batryticatus interfering with IS was predicted by systematic pharmacology method, and then it was further verified by animal experiments. The effects of Bombyx batryticatus extract on plasma coagulation were detected, and the activation of coagulation factor Ⅻ (FⅫ) and its downstream substrate kallikrein kinase (KK) was detected in vitro. The brain morphology and expressions of FXII, KK, vascular endothelial growth factors (VEGF), CD31, Brdu/von Willebrand Factor (vWF) were detected. The morphological changes, cell proliferation and VEGF expression of brain microvascular endothelial cells were detected by oxygen glucose deprivation model. The pharmacodynamic substances of Bombyx batryticatus extract were identified by Liquid Chromatography - Mass Spectrometry (LC-MS). ResultsThe results of systematic pharmacology found that the treatment of IS by Bombyx batryticatus may be related to blood coagulation and other processes. In vitro, Bombyx batryticatus extract prolonged the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) (P < 0.05), activated FⅫ and promoted the production of downstream substrate KK, with dose-dependent (P < 0.05). Bombyx batryticatus extract improved the neuronal damage of rats, activated FXII and increased the production of KK and the expressions of VEGF, CD31, Brdu/vWF (P < 0.05). Bombyx batryticatus extract also increased the proliferation of brain microvascular endothelial cells and expression of VEGF in rats (P < 0.05). A total of 809 metabolites in Bombyx batryticatus extract were identified by LC-MS. ConclusionBombyx batryticatus extract may ameliorate the injury of nerve function in rats with cerebral ischemia/reperfusion injury.

ANGPTL2+cancer-associated fibroblasts and SPP1+macrophages are metastasis accelerators of colorectal cancer.

Liver metastasis (LM) is a leading cause of cancer-related deaths in CRC patients, whereas the associated mechanisms have not yet been fully elucidated. Therefore, it is urgently needed to deeply explore novel metastasis accelerators and therapeutic targets of LM-CRC. The bulk RNA sequencing data and clinicopathological information of CRC patients were enrolled from the TCGA and GEO databases. The single-cell RNA sequencing (scRNA-seq) datasets of CRC were collected from and analyzed in the Tumor Immune Single-cell Hub (TISCH) database. The infiltration levels of cancer-associated fibroblasts (CAFs) and macrophages in CRC tissues were estimated by multiple immune deconvolution algorithms. The prognostic values of genes were identified by the Kaplan-Meier curve with a log-rank test. GSEA analysis was carried out to annotate the significantly enriched gene sets. The biological functions of cells were experimentally verified. In the present study, hundreds of differentially expressed genes (DEGs) were selected in LM-CRC compared to primary CRC, and these DEGs were significantly associated with the regulation of endopeptidase activity, blood coagulation, and metabolic processes. Then, SPP1, CAV1, ANGPTL2, and COLEC11 were identified as the characteristic DEGs of LM-CRC, and higher expression levels of SPP1 and ANGPTL2 were significantly associated with worse clinical outcomes of CRC patients. In addition, ANGPTL2 and SPP1 mainly distributed in the tumor microenvironment (TME) of CRC tissues. Subsequent scRNA-seq analysis demonstrated that ANGPTL2 and SPP1 were markedly enriched in the CAFs and macrophages of CRC tissues, respectively. Moreover, we identified the significantly enriched gene sets in LM-CRC, especially those in the SPP1+macrophages and ANGPTL2+CAFs, such as the HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION and the HALLMARK_COMPLEMENT. Finally, our in vitro experiments proved that ANGPTL2+CAFs and SPP1+macrophages promote the metastasis of CRC cells. Our study selected four characteristic genes of LM-CRC and identified ANGPTL2+CAFs and SPP1+macrophages subtypes as metastasis accelerators of CRC which provided a potential therapeutic target for LM-CRC.

Genetically encoded phosphatidylserine biosensor for in vitro, ex vivo and in vivo labelling

BackgroundThe dynamics of phosphatidylserine in the plasma membrane is a tightly regulated feature of eukaryotic cells. Phosphatidylserine (PS) is found preferentially in the inner leaflet of the plasma membrane. Disruption of this asymmetry leads to the exposure of phosphatidylserine on the cell surface and is associated with cell death, synaptic pruning, blood clotting and other cellular processes. Due to the role of phosphatidylserine in widespread cellular functions, an efficient phosphatidylserine probe is needed to study them. Currently, a few different phosphatidylserine labelling tools are available; however, these labels have unfavourable signal-to-noise ratios and are difficult to use in tissues due to limited permeability. Their application in living tissue requires injection procedures that damage the tissue and release damage-associated molecular patterns, which in turn stimulates phosphatidylserine exposure.MethodsFor this reason, we developed a novel genetically encoded phosphatidylserine probe based on the C2 domain of the lactadherin (MFG-E8) protein, suitable for labelling exposed phosphatidylserine in various research models. We tested the C2 probe specificity to phosphatidylserine on hybrid bilayer lipid membranes by observing surface plasmon resonance angle shift. Then, we analysed purified fused C2 proteins on different cell culture lines or engineered AAVs encoding C2 probes on tissue cultures after apoptosis induction. For in vivo experiments, neurotropic AAVs were intravenously injected into perinatal mice, and after 2 weeks, brain slices were collected to observe C2-SNAP expression.ResultsThe biophysical analysis revealed the high specificity of the C2 probe for phosphatidylserine. The fused recombinant C2 proteins were suitable for labelling phosphatidylserine on the surface of apoptotic cells in various cell lines. We engineered AAVs and validated them in organotypic brain tissue cultures for non-invasive delivery of the genetically encoded C2 probe and showed that these probes were expressed in the brain in vivo after intravenous AAV delivery to mice.ConclusionsWe have demonstrated that the developed genetically encoded PS biosensor can be utilised in a variety of assays as a two-component system of C2 and C2m2 fusion proteins. This system allows for precise quantification and PS visualisation at directly specified threshold levels, enabling the evaluation of PS exposure in both physiological and cell death processes.

Strong tissue adhesive polyelectrolyte complex powders based on low molecular weight chitosan for acute hemorrhage control

Self-gelling and bioadhesive powders offered promising effective hemostats to suit irregularly shaped, complex and non-compressible wounds for clinical applications. In the current study, chitosan based polyelectrolyte complex coacervate were simply prepared by mixing high concentrations (10 %) of low molecular weight chitosan (CS) and polyacrylic acid (PAA) solutions. Obtained by lyophilization, the physical cross-linked polyelectrolyte complex powders would form a gel within 5 s upon hydration, which demonstrated excellent mechanical properties, significant antibacterial activities, strong and lasting adhesion on wet tissues in physiological environment. In vitro blood clotting assays showed that the CS/PAA powders could remarkably aggregate blood cells and accelerate blood clotting process. As studied by diverse hemorrhage models, including rat tail, liver and heart injuries and dog incision, CS/PAA powders significantly facilitated the decrease of blood loss as well as hemostatic time by creating robust physical barriers and promoting blood clot formation on the bleeding sites. These outstanding properties in terms of easy preparation, rapid self-gelling, strong wet adhesion, effective hemostasis and shape-adaptability endowed CS/PAA polyelectrolyte complex powders with great potential in managing acute hemorrhage of non-compressible trauma.

Proteins journey-from marine to freshwater ecosystem: blood plasma proteomic profiles of pink salmon Oncorhynchus gorbuscha Walbaum, 1792 during spawning migration.

The pink salmon (Oncorhynchus gorbuscha) is a commercial anadromous fish species of the family Salmonidae. This species has a 2-year life cycle that distinguishes it from other salmonids. It includes the spawning migration from marine to freshwater environments, accompanied by significant physiological and biochemical adaptive changes in the body. This study reveals and describes variability in the blood plasma proteomes of female and male pink salmon collected from three biotopes-marine, estuarine and riverine-that the fish pass through in spawning migration. Identification and comparative analysis of blood plasma protein profiles were performed using proteomics and bioinformatic approaches. The blood proteomes of female and male spawners collected from different biotopes were qualitatively and quantitatively distinguished. Females differed primarily in proteins associated with reproductive system development (certain vitellogenin and choriogenin), lipid transport (fatty acid binding protein) and energy production (fructose 1,6-bisphosphatase), and males in proteins involved in blood coagulation (fibrinogen), immune response (lectins) and reproductive processes (vitellogenin). Differentially expressed sex-specific proteins were implicated in proteolysis (aminopeptidases), platelet activation (β- and γ-chain fibrinogen), cell growth and differentiation (a protein containing the TGF_BETA_2 domain) and lipid transport processes (vitellogenin and apolipoprotein). The results are of both fundamental and practical importance, adding to existing knowledge of the biochemical adaptations to spawning of pink salmon, a representative of economically important migratory fish species.

Euryale ferox stem-inspired anisotropic quaternized cellulose/xanthan-based antibacterial sponge with high absorbency and compressibility for noncompressible hemorrhage

Uncontrollable hemorrhage from deep noncompressible wounds remains an intractable challenge. Herein, inspired by the euryale ferox stem which is capable of transporting water and nutrient substances efficiently along longitudinally aligned channels, an anisotropic sponge with rapidly liquid absorption capacity, excellent mechanical compressibility and antibacterial property based on quaternized cellulose (QC), xanthan gum (XG) and reduced graphene oxide (rGO), was constructed. The euryale ferox stem-like structure and multiple interactions, involving hydrogen bonding, electrostatic interaction and chemical crosslinking, endowed the sponge with excellent fatigue resistance, elasticity and efficient liquid absorption capacity. In vivo rat liver injury, tail amputation and liver noncompressible hemorrhage model experiments confirmed that the sponge exhibited superior hemostatic performance than commercial gelatin sponge, attributing to the positive charge, efficient absorption capacity and rough surface of the sponge, which synergistically promoting the aggregation and activation of red blood cells and platelets as well as formation of fibrin network, leading to accelerated blood coagulation process. Besides, the sponge showed favorable cytocompatibility, hemocompatibility and antibacterial property. Overall, the bioinspired sponge had fantastic potential for controlling deep noncompressible hemorrhage and providing a new idea for designing hemostatic materials.

The Effect of the Thyroid Gland on High Blood Pressure

The paper discusses the relationship between the thyroid gland and high blood pressure, specifically in the context of hyperthyroidism. It explains that hyperthyroidism, characterized by an increase in thyroid hormones, can lead to an acceleration of the heartbeat and an increase in its force, resulting in high blood pressure . The paper also mentions that high blood pressure resulting from other diseases, such as thyroid problems, is known as secondary hypertension. Treating this type of high blood pressure requires addressing the underlying medical condition causing it Additionally, the paper highlights that thyroid hormones play a role in regulating hemostasis, the process of blood clotting. Thyroxine, a thyroid hormone, is associated with the release of von Will brand factor and influences the synthesis of proteins involved in hemostasis. Thyroxine deficiency in hypothyroidism can lead to a deficiency in certain clotting factors Low serum levels of T3 can increase peripheral vascular resistance by up to 30%, leading to arterial stiffness and a decrease in cardiac output. This results in high blood pressure, particularly in systolic blood pressure, which returns to normal with treatment of the underlying thyroid dysfunction. Hypothyroidism is associated with high blood pressure, and the most common cardiovascular findings in hypothyroidism are bradycardia and high blood pressure. Thyroid hormone deficiency affects the contractility of cardiomyocytes, leading to an increase in peripheral vascular resistance and diastolic dysfunction. The presence of an antigen in patients with subclinical hypothyroidism may contribute to a potential hypercoagulable state, which can further impact blood pressure regulation.

Mechanisms involved in regulation of blood coagulation: history of research and perspectives

Blood clotting is the most important physiological response in the body to disruption to vascular structure or vessel wall abnormalities. This process is non-stationary, involving many not fully established mechanisms of spatial regulation, and an understanding of this process is essential for the prevention of a large number of life-threatening conditions. This review is focused on investigations into the research of blood clotting processes by a team of biophysicists, alumni and employees of the Biophysics Department of the Faculty of Physics, Lomonosov Moscow State University, who created one of the leading Russian scientific schools for experimental and theoretical approaches to the study of the hemostasis system. The review describes the main directions of research, which included many diverse aspects of the problem - from the development of theoretical models of blood coagulation to the development and clinical studies of new methods for assessing the state of the hemostasis system.

The Gilded Clot: Review of Metal-Modulated Platelet Activation, Coagulation, and Fibrinolysis.

The processes of blood coagulation and fibrinolysis that in part maintain the physical integrity of the circulatory system and fluidity of its contents are complex as they are critical for life. While the roles played by cellular components and circulating proteins in coagulation and fibrinolysis are widely acknowledged, the impact of metals on these processes is at best underappreciated. In this narrative review we identify twenty-five metals that can modulate the activity of platelets, plasmatic coagulation, and fibrinolysis as determined by in vitro and in vivo investigations involving several species besides human beings. When possible, the molecular interactions of the various metals with key cells and proteins of the hemostatic system were identified and displayed in detail. It is our intention that this work serve not as an ending point, but rather as a fair evaluation of what mechanisms concerning metal interactions with the hemostatic system have been elucidated, and as a beacon to guide future investigation.

Lactaderhin's C1 domain restricts protein's ensemble as it binds to charged membranes.

Lactadherin's (Lact) binding to phosphotidylserine (PS) enriched cell surfaces is critical for controlling our blood coagulation. Although structural and mutagenesis studies indicate important binding regions of this protein, they are not sufficient to construct a detailed, membrane-bound model especially since they mainly consider only one of its two globular domains, namely C2. We thus use molecular dynamics (MD) simulations and the AlphaFold program to generate an ensemble of Lact encounter complexes with a negatively charged bilayer consistent with biochemical studies. This was accomplished by first using the highly mobile membrane mimetic (HMMM) to efficiently simulate its C2 domain binding to PS lipids. We then converted the HMMM model to standard full-tail lipid membranes to further sample and obtain converged bound structures that we call the “vertical” and “side-lying” ensembles. From these bilayer-bound poses, we infer which one allows for attachment of its other C1 domain and use AlphaFold to reconstruct it and further simulate to capture equilibrium complexes. Modeling revealed that C1 domain restricts the dynamics structural ensemble of Lact bound to membranes. We also report Lact's full dynamic structure in the presence of negatively charged lipids and compare them with other homologous blood coagulation proteins to provide a rationale for its competitive binding. These results shed light on the structural mechanism of blood coagulation by considering its binding in a membrane environment which can serve as a general framework for studying these critical protein-membrane interactions. They also provide a structural basis for further understanding the significance that PS lipids play in regulating blood coagulation processes.