Heparin Molecules Research Articles

Study on Heparin-Induced Thrombocytopenia and Blood Group among Individuals Suffering from Acute Coronary Syndrome

Background: Clinicians confront heparin-induced thrombocytopenia (HIT) as the most pertinent pathological relationship. Antibodies directed against complexes of heparin molecules and platelet factor 4 (PF4) are the cause of this immune-mediated phenomena. HIT is a significant adverse event that affects individuals with acute coronary syndromes (ACS). Objective: To assess the frequency of HIT in patients presenting with ACS. Materials and Methods: This study was carried out the Northeast Medical College's Department of Cardiology in Sylhet from June 2021 to December 2022. A total of 234 individuals aged 40 to 70 years old presented with ACS within 24 hours of symptom onset. This study excluded patients with idiopathic thrombocytopenic purpura (ITP), aplastic anemia, myeloproliferative diseases, or pre-existing thrombocytopenia. Thrombocytopenia was evaluated using medical records and a full blood count (CBC), with isolated thrombocytopenia (platelets <150 x109/L) prior to heparin administration. Results: Diabetes mellitus, hypertension, a history of ACS, and obesity were the most frequent comorbidities, accounting for 41.03%, 33.76%, 43.16%, and 14.96%, respectively. The incidence of HIT in NSTEMI and STEMI was higher than in unstable angina, although still comparable. The delayed presentation of ACS > 12 hours was also strongly correlated with the occurrence of HIT (p<0.05). Unstable angina and middle age (50–60 years) were found to have a significant relationship with HIT (p<0.05). Conclusion: HIT is more common in patients who have had a myocardial infarction or who have had symptoms for more than 12 hours at the time of hospitalization. Cardiologists and internal medicine experts must take extra precautions when administering heparin to high-risk patients to prevent problems.

Silk Fibroin-Based Scaffolds: Potential for Applications in Wound Healing

Chronic wounds, such as diabetic foot ulcers, pose significant challenges due to their prolonged inflammation state, slow vascularization, lack of supportive matrix, and frequent recurrence. Biocompatible materials like silk fibroin (SF) and collagen can be promising in chronic wound healing applications due to their biocompatibility, and ability to act as supporting matrix necessary for tissue regeneration. This study explores the development and characterization of SF-based biomaterials in various formats, including gels, lyophilized scaffolds, and films, by combining them with collagen (Col) and heparin (Hep) molecules that are known for the wound-healing properties. SF gels, films, and lyophilized scaffolds were characterized for water retention capacity, porosity, contact angle, and antibacterial properties. Curcumin-loaded films reported moderate wetting behavior but were brittle, thin and hard. Freeze-dried scaffolds possessed higher water retention capacity compared to the sonicated gels and films, and showed a porous network structure, while the fabricated SF gels disintegrated in water. SF with a chelating agent demonstrated mild antibacterial properties, which were retained when combined with Collagen peptides and Heparin. The antimicrobial effect was significantly enhanced when SF+Col+Hep was added with antimicrobial agents such as Gentamicin and Ceftriaxone. The study concludes that SF-based scaffolds, particularly those incorporating collagen peptides and heparin, can be leveraged for molecular delivery application towards wound healing. Future research should focus on improving mechanical properties, measuring release kinetics of heparin and other biomolecules from SF-based lyophilized scaffolds, and conducting in vivo studies to validate the therapeutic value.

Abstract Tu007: The Impact of Shear-Thinning Hydrogel Delivery on Extracellular Vesicle Cardiac Retention

Background: Extracellular vesicles (EVs) are essential mediators of intercellular communication. EVs secreted by cardiosphere-derived cells (CDC-EVs) hold promise as vectors in the context of cardiac repair and remodeling through modulation of cardiomyocyte apoptosis and the immune response following injury. Cardiac retention of CDC-EVs is a critical factor influencing their therapeutic efficacy as first-pass uptake and washout from the myocardium remains a variable. We hypothesized that loading CDC-EVs in a shear-thinning, hybrid hydrogel would provide sustained myocardial delivery and reduced EV extraction by the lungs. Methods: The hydrogel system was constructed via a two-step approach utilizing Michael-addition reaction and host-guest complexation. This system incorporates four components: (1) an adamantane-functionalized multi-arm polyethylene glycol, (2) monosubstituted β-cyclodextrin-maleimide, (3) a thiolated hyaluronic acid, and (4) a heparin molecule containing thiol moieties. Following LAD ligation, intramyocardial injections of DiR-labeled EVs or hydrogel-encapsulated DiR-labeled EVs were performed on mice. Animals were euthanized after 24 hours and organs harvested. Whole organ biofluorescence was performed using IVIS Spectrum imaging. Results: Hydrogel-encapsulated EVs exhibited enhanced cardiac retention 24 hours post-MI when compared with EVs without hydrogel (17 ± 4.4 vs. 3.4 ± 0.9, mean radiant efficiency as a % of dose ± SEM, p<0.01 using unpaired two-tailed t-test). Mice treated with hydrogel encapsulated EVs showed reduced EV retention in the lungs compared to controls treated with EVs alone (5.7 ± 0.9 vs. 10.6 ± 1.4, mean radiant efficiency as a % of dose ± SEM, p<0.05 using unpaired two-tailed t-test). Conclusion: Usage of shear-thinning hydrogel as an EV delivery vehicle enhances EV retention in the heart and decreases off-target uptake of EVs following acute MI. This finding suggests that hydrogel delivery may be a promising strategy to improve the therapeutic efficacy of CDC-EVs for cardiac repair.

Small molecules targeting GRP78 mitigate anti-GRP78 autoantibody–mediated tissue factor procoagulant activity in cultured endothelial cells

BackgroundThe 78-kDa glucose-regulated protein (GRP78) expressed on the cell surface (csGRP78) has been reported to regulate tissue factor (TF) procoagulant activity (PCA) in lesion-resident endothelial cells (ECs), which is further enhanced by circulating anti-GRP78 autoantibodies that bind to the Leu98-Leu115 epitope in GRP78. ObjectivesDetermine the effects of the engagement of the anti-GRP78 autoantibody to csGRP78 on ECs and the underlying mechanisms that impact TF PCA. MethodsImmunofluorescent staining was used to determine the presence of csGRP78 in tumor necrosis factor α–treated ECs. An established TF PCA assay was used to evaluate human ECs following treatment with anti-GRP78 autoantibodies. The Fura 2-AM assay (Abcam) was used to quantify changes in intracellular Ca2+ levels. Small molecules predicted to bind GRP78 were identified using artificial intelligence. Enzyme-linked immunosorbent assays were used to assess the ability of these GRP78 binders to mitigate TF activity and interfere with the autoantibody/csGRP78 complex. ResultsIn tumor necrosis factor α–treated ECs, anti-GRP78 autoantibodies increased TF PCA. This observation was further enhanced by endoplasmic reticulum stress-induced elevation of csGRP78 levels. Anti-GRP78 autoantibody treatment increased intracellular Ca2+ levels. Sequestering the anti-GRP78 autoantibody with a conformational peptide or blocking with heparin attenuated anti-GRP78 autoantibody–induced TF PCA. We identified B07∗, as a GRP78 binder that diminished anti-GRP78 autoantibody–induced TF PCA on ECs. ConclusionThese findings show how anti-GRP78 autoantibodies enhance TF PCA that contributes to thrombosis and identify novel GRP78 binders that represent a potential novel therapeutic strategy for treating and managing atherothrombotic disease.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units, and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody-negative patients. We observed statistical differences between antibody-positive and -negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody-positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

Tumor targeting in situ aggregation of nanoparticle-to-nanoparticle strategy to simultaneously induce ferroptosis and immunogenic cell death using complementary heparin and protamine molecules

Antibody-drug conjugate (ADC)-based tumor-targeting therapies have demonstrated clinical success in selective drug delivery for cancer treatment. However, the effectiveness of these strategies is hindered by the low amount of loaded payload, lack of sustained efficacy, and insufficient therapeutic performance. In this study, we introduce a novel in situ aggregation-based targeting system using two combinable nanoparticles (NP) that leverage the biocompatible and specific interaction between complementary protamine and heparin molecules. To demonstrate it, we developed protamine-based nanoparticles (PPNC NP) containing cytotoxic negatively charged curcumin (NCur), and heparin-based nanoparticles (HDFe NP) encapsulating doxorubicin and Fe3+. The NP-NP treatment successfully formed aggregates at targeted tumor sites. Our findings demonstrate that the initial administration of PPNC NP effectively targets the tumor and the subsequent administration of complementary HDFe NPs results in their significant accumulation in the tumor tissue, directed by the ‘guidance effect’ of PPNC NPs. This sequence of events promotes the formation of in situ aggregates within the tumor tissue, leading to prolonged nanoparticle accumulation, ferroptosis and immunogenic cell death (ICD). In conclusion, our study demonstrates the effectiveness of a biocompatible and in situ aggregating nanoparticle-nanoparticle system as a solution for overcoming the limitations of current nanoparticle-based delivery systems.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody negative patients. We observed statistical differences between antibody positive and negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

Modified Diatomaceous Earth in Heparin Recovery from Porcine Intestinal Mucosa.

Heparin, a highly sulfated glycosaminoglycan, is a naturally occurring anticoagulant that plays a vital role in various physiological processes. The remarkable structural complexity of heparin, consisting of repeating disaccharide units, makes it a crucial molecule for the development of commercial drugs in the pharmaceutical industry. Over the past few decades, significant progress has been made in the development of cost-effective adsorbents specifically designed for the adsorption of heparin from porcine intestinal mucosa. This advancement has been driven by the need for efficient and scalable methods to extract heparin from natural sources. In this study, we investigated the use of cationic ammonium-functionalized diatomaceous earth, featuring enhanced porosity, larger surface area, and higher thermal stability, to maximize the isolated heparin recovery. Our results showed that the higher cationic density and less bulky quaternary modified diatomaceous earth (QDADE) could adsorb up to 16.3 mg·g-1 (31%) of heparin from the real mucosa samples. Additionally, we explored the conditions of the adsorbent surface for recovery of the heparin molecule and optimized various factors, such as temperature and pH, to optimize the heparin uptake. This is the introductory account of the implementation of modified diatomaceous earth with quaternary amines for heparin capture.

Extension of the SUGRES-1P Coarse-Grained Model of Polysaccharides to Heparin.

Heparin is an unbranched periodic polysaccharide composed of negatively charged monomers and involved in key biological processes, including anticoagulation, angiogenesis, and inflammation. Its structure and dynamics have been studied extensively using experimental as well as theoretical approaches. The conventional approach of computational chemistry applied to the analysis of biomolecules is all-atom molecular dynamics, which captures the interactions of individual atoms by solving Newton's equation of motion. An alternative is molecular dynamics simulations using coarse-grained models of biomacromolecules, which offer a reduction of the representation and consequently enable us to extend the time and size scale of simulations by orders of magnitude. In this work, we extend the UNIfied COarse-gRaiNed (UNICORN) model of biological macromolecules developed in our laboratory to heparin. We carried out extensive tests to estimate the optimal weights of energy terms of the effective energy function as well as the optimal Debye-Hückel screening factor for electrostatic interactions. We applied the model to study unbound heparin molecules of polymerization degree ranging from 6 to 68 residues. We compare the obtained coarse-grained heparin conformations with models obtained from X-ray diffraction studies of heparin. The SUGRES-1P force field was able to accurately predict the general shape and global characteristics of heparin molecules.

Progress in Application of Heparin Coating in Blood Contact Medical Devices

Blood compatibility is the main restriction of blood-contacting medical devices in clinical application, especially long-term blood-contacting medical devices will stimulate the immune defense mechanism of the host, resulting in thrombosis. Heparin anticoagulant coating links heparin molecules to the surface of medical device product materials, improves the compatibility between the material surface interface and the body, and reduces the host immune defense reactions. This study reviews the structure and biological properties of heparin, the market application status of heparin-coated medical products, the insufficiency and improvement of heparin coating, which can provide a reference for the application research of blood contact medical devices.

Doxorubicin covalently conjugated heparin displays anti-cancer activity as a self-assembled nanoparticle with a low-anticoagulant effect

Heparin is a glycosaminoglycans (GAGs) member and well-known FDA-approved anticoagulant that has been widely used in the clinic for 100 years. It has also been evaluated in various fields for further clinical applications, such as in anti-cancer or anti-inflammatory therapy beyond its anticoagulant effect. Here, we sought to utilize heparin molecules as drug carriers by directly conjugating the anticancer drug doxorubicin to the carboxyl group of unfractionated heparin. Given the molecular action of doxorubicin in intercalating DNA, it is expected to be less effective when structurally combined with other molecules. However, by utilizing doxorubicin molecules to produce reactive oxygen species (ROS), we found that the heparin–doxorubicin conjugates have significant cytotoxic ability to kill CT26 tumor cells with low anticoagulant activity. Several doxorubicin molecules were bound to heparin to provide sufficient cytotoxic capability and self-assembly ability due to their amphiphilic properties. The self-assembled formation of these nanoparticles was demonstrated through DLS, SEM and TEM. The cytotoxic ROS-generating doxorubicin-conjugated heparins could inhibit tumor growth and metastasis in CT26-bearing Balb/c animal models. Our results demonstrate that this cytotoxic doxorubicin-based heparin conjugate can significantly inhibit tumor growth and metastasis, thus showing promise as a potential new anti-cancer therapeutic.

The centrality of proteoglycan research: Expect the unexpected

The centrality of proteoglycan research: Expect the unexpected

Efficient and Economic Heparin Recovery from Porcine Intestinal Mucosa Using Quaternary Ammonium-Functionalized Silica Gel

Heparin, usually isolated from porcine intestinal mucosa, is an active pharmaceutical ingredient of great material value. Traditionally, diverse types of commercial resins were employed as an adsorbent for heparin retrieval from biological samples. However, more recent years have encouraged the advent of new cost-effective adsorbents to achieve enhanced heparin retrieval. Inexpensive cationic ammonium-functionalized silica gels, monodispersed with larger surface area, porosity, and higher thermal stability, were chosen to evaluate the heparin recovery yield from porcine intestinal mucosa. We demonstrated that higher positively charged and less bulky quaternary modified silica gel (e.g., QDASi) could adsorb ~28% (14.7 mg g-1) heparin from the real samples. In addition, we also determined suitable surface conditions for the heparin molecule adsorption by mechanistic studies and optimized different variables, such as pH, temperature, etc., to improve the heparin adsorption. This is going to be the first reported study on the usage of quaternary amine-functionalized silica gel for HEP uptake.

Collagen-Based Osteogenic Nanocoating of Microrough Titanium Surfaces.

The aim of the present study was to develop a collagen/heparin-based multilayer coating on titanium surfaces for retarded release of recombinant human bone morphogenic protein 2 (rhBMP2) to enhance the osteogenic activity of implant surfaces. Polyelectrolyte multilayer (PEM) coatings were constructed on sandblasted/acid-etched surfaces of titanium discs using heparin and collagen. PEM films of ten double layers were produced and overlayed with 200 µL of a rhBMP2 solution containing 15 µg rhBMP2. Subsequently, cross-linking of heparin molecules was performed using EDC/NHS chemistry to immobilize the incorporated rhBMP2. Release characteristics for 3 weeks, induction of Alkaline Phosphatase (ALP) in C2C12 cells and proliferation of human mesenchymal stem cells (hMSCs) were evaluated to analyze the osteogenic capacity of the surface. The coating incorporated 10.5 µg rhBMP2 on average per disc and did not change the surface morphology. The release profile showed a delivery of 14.5% of the incorporated growth factor during the first 24 h with a decline towards the end of the observation period with a total release of 31.3%. Cross-linking reduced the release with an almost complete suppression at 100% cross-linking. Alkaline Phosphatase was significantly increased on day 1 and day 21, indicating that the growth factor bound in the coating remains active and available after 3 weeks. Proliferation of hMSCs was significantly enhanced by the non-cross-linked PEM coating. Nanocoating using collagen/heparin-based PEMs can incorporate clinically relevant amounts of rhBMP2 on titanium surfaces with a retarded release and a sustained enhancement of osteogenic activity without changing the surface morphology.

Heparinization of the bovine pericardial scaffold by layer-by-layer (LBL) assembly technique

The bovine pericardium has been introduced to tissue engineering as a highly versatile material. Bovine pericardial scaffolds (BPSs) have been fabricated and presented good mechanical properties and biocompatibility. In the cardiovascular field, thrombogenicity is the main obstacle limiting the effectiveness of BPSs due to thrombus formation. Heparinization is a potential approach to improve the hemocompatibility of engineered constructs derived from decellularized tissues. In this study, we report on BPSs heparinized by the Layer-by-Layer self-assembly (LbL) technique. Heparin was immobilized on BPSc by introducing linkage of heparin and dihydroxy-iron (DHI). The oppositely charged heparin and DHI were alternatively deposited on the surface of BPSc microfibers via the desired number of LbL cycles. Hematoxyline and eosin (H&E) staining, scanning electron microscopy (SEM), and Toluidine Blue O (TBO) assay were used to evaluate the morphology and efficacy of heparinized BPSs. The anticoagulant activity was assessed by incubating the tested materials with blood. Histological evidence indicated the heparin deposition when increasing the number of LbL cycles. SEM observations revealed Heparin-DHI complex coatings onto the microfibrils of the scaffold. In comparison with simple incubation, more heparin molecules are effectively linked to the scaffolds when using the LbL technique in the presence of DHI. Heparin contents in the BPS samples significantly varied with the number of LbL cycles. The heparinized membranes exhibited the resistance to blood clotting upon blood-contacting. Furthermore, heparin-DHI multilayer coating was shown to maintain good anticoagulation activity over a 30-day release period. Finding results verified the successful heparinization of the BPSs by the Layer-by-Layer self-assembly technique. The heparinized bovine pericardial scaffolds could be valuable candidate material in the cardiovascular field.

Comparison of three methods including temperature, H2O2/ascorbic acid/sonication, and nitrous acid treatments for overcoming the inhibitory effect of heparin on DNA amplification in realtime-PCR

Heparin molecules have an inhibitory effect on DNA amplification by binding to the majority of DNA-interacting proteins. Different physical, chemical, and enzymatic methods have been used to degrade and depolymerize heparins in biomedical investigations. In this study, we aimed to evaluate some heparin degradation methods to eliminate the inhibitory effect of heparin on DNA amplification. Here, we report highly efficient, simple, and convenient methods to eliminate the heparin inhibitory effect on DNA amplification by treatments including temperature, nitrous acid, and H2O2/ascorbic acid/sonication. Further, treatment conditions including temperature degree and duration of treatments, the concentration of ascorbic acid, and intensity of sonication were reviewed. Target DNAs were extracted using the phenol-chloroform method. DNA concentrations and purity were analyzed before and after each treatment by Nanodrop spectrophotometry. DNA amplifications were attempted using a commercially available realtime-PCR mastermix. We found that the inhibitory behavior of heparin was well eliminated after the 85 °C/2 h, 65 °C/2 h, nitrous acid (pH = 3), and H2O2/ascorbic acid/sonication treatments, respectively. The further analyses indicated that the application of nitrous acid in pH = 1.5 and H2O2/ascorbic acid/sonication in higher ascorbic acid concentrations and sonication intensities lead to failure in DNA amplification due to the degradation of target sequences. From our experience, simple heat treatments or at the next level using nitrous acid and H2O2/ascorbic acid/sonication have enabled the detection and quantification of virus infection in heparin blood samples. These approaches may enable researchers to utilize blood taken in heparin tubes for genome amplification and diagnostic purposes.

Substitution-inert polynuclear platinum complexes and Glycosaminoglycans: A molecular dynamics study of its non-covalent interactions

An impressive class of formally substitution-inert polynuclear platinum complexes known as Substitution-inert Polynuclear Platinum (II) Complexes (SI-PPCs) present an attractive approach for medicinal inorganic chemistry through high-affinity non-covalent interactions with biomolecules, such as DNA and Glycosaminoglycans (GAGs). This interaction occurs through the formation of non-covalent cyclic structures called clamps and forks with the phosphate and sulfate groups present in these biomolecules. This work shows several analyses of the non-covalent interactions formed between heparin (PDB code: 1HPN) and SI-PPCs obtained through molecular dynamics (MD) simulations. Root Mean Square Deviation (RMSD) results showed that the “non-covalent” di-nuclear platinum compound, DiplatinNC ([{trans-Pt(NH3)2(NH2(CH2)6NH3+)}2-μ-NH2(CH2)6NH2]6+) and AH44 ([{Pt(NH3)3}2{(μ-(H2N(CH2)6NH2)2-(trans-Pt(NH3)2}]6+, 0,0,0/t,t,t,) complexes, which are both 6+ charged complexes, were the most rigid. On the other hand, the Root Mean Square Fluctuation (RMSF) showed that there is a reduction in the atomic fluctuation of atoms in the central region of the heparin molecule; the solvent accessible surface area (SASA) analysis also indicates a reduction in the accessible area by the heparin when interacting with SI-PPCs. The evaluation of H-Bond data confirms the formation of the non-covalent interactions, which may suggest a decrease in the action of 1HPN by preventing the action of enzymes on this substrate. In addition, thermodynamic results indicate that this interaction is spontaneous, considering the negative variations in the Gibbs free energy presented by the studied systems.

Efficient Heparin Recovery from Porcine Intestinal Mucosa Using Zeolite Imidazolate Framework-8.

Heparin is one of the most valuable active pharmaceutical ingredients, and it is generally isolated from porcine intestinal mucosa. Traditionally, different types of commercial resins are employed as an adsorbent for heparin uptake; however, using new, less expensive adsorbents has attracted more interest in the past few years to enhance the heparin recovery. Zeolite imidazolate framework-8 (ZIF-8), as a metal–organic framework (MOF) with a high surface area, porosity, and good stability at high temperatures, was selected to examine the heparin recovery. In this research, we demonstrate that ZIF-8 can recover up to ~70% (37 mg g−1) of heparin from porcine intestinal mucosa. A mechanistic study through kinetic and thermodynamic models on the adsorption revealed appropriate surface conditions for the adsorption of heparin molecules. The effect of different variables such as pH and temperature on heparin adsorption was also studied to optimize the recovery. This study is the first to investigate the usage of MOFs for heparin uptake.

Fabrication of polyurethane – Heparinized carbon nanotubes composite for heart valves application

In this study, nanocomposites based on polyurethane - carbon nanotubes modified with heparin was made to use in heart valves which was then modified through sulfuric acid and nitric acid oxidization. The next step was acylation reaction that replaced with chlorine molecules. Then amine groups attached to nano fillers in order to physical reaction of heparin molecules. The functionalized carbon nanotubes were characterized using fourier transform infrared spectra (FTIR), elemental analysis and thermogravimetric analysis (TGA) assessments. The morphology of nanocomposites was investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, dynamic mechanical thermal analysis (DMTA) used to determine thermo-mechanical properties of nanocomposites. To observe the effect of grafted heparin to the surface of carbon nanotubes, the hydrophilicity properties were observed through contact angle measurement, and to evaluate activation grafted heparin the activated partial trombobelastine time (APTT) test was performed. Finally, to investigate the effect of nanocomposites on blood components such as platelet, platelet adhesion test was performed on the surface of nanocomposites. The results revealed that occurrence of successful functionalization reaction. Heparin is a sulfated drug that has a hydrophilic property. The test results showed that the hydrophilicity properties were enhanced by increasing the amount of heparin that confirms heparin molecules grafted on the surface of nanoparticles successfully. The APTT test also showed the grafted heparin was activated. Examination of platelet adhesion on the surface of heparinized nanocomposites revealed that with increasing the percentage of heparin in nanocomposites, platelet adhesion and accumulation on the surface of nanocomposites decreased, making it a promising candidate for further studies towards heart valve applications.

Mast Cells Heparin — New Information on the Old Component (Review)

Mast cells (MC) are widely distributed throughout the body of animals and humans, mainly in barrier tissues. This review provides new information on the hematopoietic origin of MCs from early erythromyeloid progenitors (EMPs), late EMPs, and definitive hematopoietic stem cells. As well as information on the maturation of MSs and heparin synthesis already in the embryonic period. Many physiological functions of MCs are determined by the properties of heparin, which forms the basis of the matrix of granules, since the heparin molecule is a strong polyanion, capable to forming complexes with many biologically active substances and regulating their properties. In a new hypothesis about the participation of MCs in pathological processes, it is assumed that this is due to the depletion of the heparin pool. In such cases, injections of exogenous heparin can help replenish MCs heparin stores. As a result of the restoration of the physiological functions of MCs and the action of exogenous heparin, the pathological process will be converted into an adaptive one. In clinical practice, unfractionated heparin (UFH) obtained from natural sources and low molecular weight heparin (LMWH) obtained by the biochemical route are used. Most often, UFH and LMWH are used in the clinic only as anticoagulants. The worldwide spread of a disease named COVID-19 in 2020 showed that UFH and LMWH are multifunctional drugs that have saved many people. The pandemic caused by COVID-19 has been an unprecedented social and health emergency worldwide. Depression, anxiety and post-traumatic stress disorder (PTSD) have been reported in populations of many countries. This review provides new information on experimental studies on the successful treatment of pathology with low doses of UFH in modeling PTSD in animals. Consequently, heparin can be considered as a promising multifunctional drug for effective pharmacological correction of comorbid diseases under the influence of extreme factors.