Anticoagulant Properties Research Articles

Recent Advances in the Therapeutic Potential of Fucoidan: A Comprehensive Review

Fucoidan, a polysaccharide primarily comprised of l-fucose and sulfate groups possesses a unique chemical structure that underpins its notable therapeutic potential. Its remarkable biological functions such as antioxidant, anticarcinogenic, antiviral, anticoagulant, antithrombotic, immunoregulatory, and anti-inflammatory properties have gained substantial recognition in the global food and pharmaceutical industries. This review highlights recent advancements in understanding fucoidan’s potential biological activities that could innovate treatments for oral infections and inflammatory diseases. A systematic search for relevant articles published between January 2000 and July 2024 was conducted across multiple databases, including PubMed, Scopus, Web of Science, and Google Scholar. Manual searches of references listed in the identified publications were conducted to ensure thorough coverage of the subject. The inclusion criteria focused on peer-reviewed articles in English-language, encompassing meta-analysis, randomized clinical trials, cohort studies, case-control studies and in vitro studies. Exclusion criteria comprised abstracts, opinion pieces, review articles not providing original analysis, and studies not directly addressing the therapeutic effects of fucoidan. This rigorous selection process aims to encapsulate the most significant and recent scientific evidence regarding the therapeutic applications of fucoidan. Fucoidans, with their diverse pharmacological properties, hold promising therapeutic potential which could emerge as a novel therapeutic option for treating wide range of diseases. Fucoidans have demonstrated anti-inflammatory properties, which may be beneficial in reducing inflammation related to periodontal diseases and other oral conditions. We anticipate that this review will serve as a foundational guide and inspire continued product development centered on fucoidan. Clinical relevance to interdisciplinary dentistry:  Fucoidan, a polysaccharide rich in fucose holds wide pharmacological effects  Enhancement of oral health outcomes through anti- inflammatory properties  Antimicrobial activity against oral pathogens  Wound healing property may aid in periodontal diseases.

Ulva sp.'nin aktif bileşiklerinin elde edilmesi için ekstraksiyon koşullarının optimizasyonu

Ulva sp., a green macroalgae known as sea lettuce, is rich in polysaccharides, proteins, minerals, and bioactive compounds with antimutagenic, anticoagulant, anticancer, anti-inflammatory, antibacterial, and nutraceutical properties. Its abundance along the Aegean Sea coast poses an environmental challenge, as it is often disposed of as waste. However, Ulva sp. holds potential for high-value products in cosmetics and dietary supplements. Optimizing the extraction of its bioactive compounds using response surface methodology involved adjusting ethanol concentration, solid/liquid ratio, and extraction time. Key responses evaluated included yield, total polysaccharides, total protein, total phenol, total antioxidant activity, alpha-glucosidase inhibitory activity, and yeast cell glucose uptake. In this study, extraction yields ranged from 0.86% to 22.47% based on variations in extraction conditions. The highest total protein content was 106.88 mg BSA/g dry extract, while the polysaccharide content was determined to be 15.42%. The highest values for total phenol content and antioxidant capacity were found to be 82.15 mg GAE/g dry extract and 63.63 mg Trolox/g dry extract, respectively. The determination of the total amounts of antioxidants and phenolic compounds in extracts may expand their potential applications. In addition, the potential application of Ulva sp extracts as inhibitors for the treatment of diabetes has been demonstrated through experiments assessing both alpha-glucosidase enzyme inhibition and glucose uptake in yeast cells. The results support an environmentally friendly approach for the utilization of Ulva sp. from waste into valuable antidiabetic products.

Study on the Bioactivity Response of the Newly Developed Zn-Cu-Mn/Mg Alloys for Biodegradable Implant Application.

Scaffolds play a crucial role in bone tissue engineering to support the defect area through bone regeneration and defect reconstruction. Promising tissue regeneration without negative repercussions and avoidance of the lifelong presence inside the body make bioresorbable metals prosper in the field of regenerative medicine. Recently, Zn and its alloys have emerged as promising biodegradable materials for their moderate degradation rate and satisfactory biocompatibility. Nevertheless, it is very challenging for cells to adhere and grow over the Zn surface alone, which influences the tissue-implant integration. In this study, an attempt has been made to systematically investigate the bioactivity responses in terms of in vitro hemocompatibility, cytotoxicity, antibacterial activity, and in vivo biocompatibility of newly developed Zn-2Cu-0.5Mn/Mg alloy scaffolds with different surface roughness. The rough surface of Zn-2Cu-0.5Mg shows the highest degradation rate of 0.16 mm/yr. The rough surface exhibits a prominent role in the adsorption of protein, further enhancing cell adhesion. Concentration-dependent alloy extract shows the highest cell proliferation for 12.5% of the extract with a maximum cell viability of 101% in Zn-2Cu-0.5Mn and 108% in Zn-2Cu-0.5Mg after 3 d. Acceptable hemolysis percentages (less than 5%) with promising anticoagulation properties are observed for all of the conditions. Enhanced antibacterial (Staphylococcus aureus and Escherichia coli) activity due to a significant effect of ions illustrates the maximum killing effect on the bacterial colony for the rough Zn-2Cu-0.5Mg alloy. In addition, it is observed that for rough Zn-2Cu-0.5Mn/Mg alloys, the inflammatory response is minimal after subcutaneous implantation, and neo-bone tissue forms in the defect areas of the rat femur with satisfactory biosafety response. The osseointegration property of the Zn-2Cu-0.5Mg alloy is comparable to that of the Zn-2Cu-0.5Mn alloy. Therefore, the rough surface of the Zn-2Cu-0.5Mg alloy has the potential to enhance biocompatibility and promote better osseointegration activity with host tissues for various biomedical applications.

Probiotic Lactobacillus salivarius mediated synthesis of silver nanoparticles (AgNPs-LS): A sustainable approach and multifaceted biomedical application

Biogenic synthesis of silver nanoparticles (AgNPs) has emerged as an eco-friendly and sustainable approach with diverse biological applications. This study presents synthesis of AgNPs-LS using a probiotic strain Lactobacillus salivarius (L. salivarius) and explores their multifaceted biological activities, including antibacterial, antibiofilm, anti-quorum sensing, antifungal, antioxidant, anticancer, anticoagulant and thrombolytic properties. The biosynthesis of AgNPs-LS was successfully achieved using L. salivarius cell free supernatants, resulting in well-characterized nanoparticles as confirmed by UV–Vis spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS) and zeta potential analysis. The AgNPs-LS demonstrated potent antibacterial activity against different pathogenic bacteria (C. violaceum, P. aeruginosa, S. aureus, E. coli and S. marcescens), emphasizing their potential in combating bacterial infections. Moreover, these AgNPs-LS were effective in inhibiting biofilm formation (>60 % at 1/2 MIC), a key mechanism of bacterial virulence, highlighting their utility in preventing biofilm-related infections. AgNPs-LS exhibited anti-quorum sensing activity, disrupting bacterial communication systems and potentially reducing virulence factor such as, violacein production in C. violaceum, pyocyanin production in P. aeruginosa and prodigiosin production in S. marcescens. Additionally, AgNPs-LS also exhibited notable antifungal activity towards a different pathogenic fungus (F. proliferatum, P. purpurogenum, A. niger and R. stolonifer). In terms of health applications, the AgNPs-LS displayed significant antioxidant activity, effectively scavenging DPPH• (IC50 = 42.65 μg/mL) and ABTS•+ (IC50 = 53.77 μg/mL) free radicals. Furthermore, AgNPs-LS showed cytotoxicity against breast cancer cells (MCF-7) (IC50 = 52.29 μg/mL), positioning them as promising candidates for cancer therapy. Moreover, AgNPs-LS were also shown promising anticoagulant and thrombolytic activities under practical conditions. Therefore, the biogenic synthesis of AgNPs-LS using L. salivarius offers a sustainable and cost-effective route for producing AgNPs with an array of biological activities. These AgNPs-LS have the potential to address various challenges in healthcare, ranging from antimicrobial, anticancer applications to biofilm inhibition, antioxidant therapy, anticoagulant and thrombolytic agents.

Evaluation of the Pharmaceutical Activities of Chuanxiong, a Key Medicinal Material in Traditional Chinese Medicine.

Szechwan lovage rhizome (SLR, the rhizome of Ligusticum chuanxiong Hort., Chuanxiong in Chinese transliteration) is one Chinese materia medica (CMM) commonly used to activate blood circulation and remove blood stasis. SLR is applicable to most blood stasis syndromes. It has significant clinical efficacy in relation to human diseases of the cardiocerebrovascular system, nervous system, respiratory system, digestive system, urinary system, etc. Apart from China, SLR is also used in Singapore, Malaysia, the European Union, and the United States of America. However, the current chemical markers in pharmacopeia or monography for the quality assessment of SLR are not well characterized or specifically characterized, nor do they fully reflect the medicinal efficacy of SLR, resulting in the quality of SLR not being effectively controlled. CMM can only have medicinal efficacy when they are applied in vivo to an organism. The intensity of their pharmaceutical activities can more directly represent the quality of CMM. Therefore, the chemical constituents and pharmacological actions of SLR are reviewed in this paper. In order to demonstrate the medicinal efficacy of SLR in promoting blood circulation and removing blood stasis, bioassay methods are put forward to evaluate the pharmaceutical activities of SLR to improve hemorheology, hemodynamics, and vascular microcirculation, as well as its anti-platelet aggregation and anticoagulation properties. Through comprehensive analyses of these pharmaceutical properties, the quality and therapeutic value of SLR are ascertained.

Constructing sodium alginate/carboxymethyl chitosan coating capable of catalytically releasing NO or CO for improving the hemocompatibility and endothelialization of magnesium alloys

Although significant progress in developing biodegradable magnesium alloy materials in cardiovascular stents has been achieved recently, they still face challenges such as rapid in vivo corrosion degradation, inferior blood compatibility, and limited re-endothelialization after the implantation. Hydrogel coating that can catalyze the liberation of gas signal molecules offers a good solution to alleviate the corrosion rate and enhance the biocompatibility of magnesium and its alloys. In this study, based on alkaline heat treatment and construction of polydopamine coating on the surface of magnesium alloy, sodium alginate/carboxymethyl chitosan (SA/CMCS) gel was simultaneously covalently grafted onto the surface to build a natural polymer hydrogel coating, and selenocystamine (SeCA) and CO release molecules (CORM-401) were respectively immobilized on the surface of the hydrogel coating to ameliorate the anticoagulant performance and accelerate endothelial cells (ECs) growth by catalyzing the release of endogenous gas signal molecules (NO or CO). The findings verified that the as-prepared hydrogel coating can catalyze the liberation of CO or NO and significantly improve the corrosion resistance of magnesium alloy. At the same time, owing to the excellent hydrophilicity of the hydrogel coating, the good anticoagulant property of sodium alginate, and the ability of CMCS to promote the ECs growth, the modified magnesium alloy could significantly improve the albumin adsorption while preventing the adsorption of fibrinogen, hence significantly augmenting the anticoagulant properties and promoting the ECs growth. Under the catalytic release of NO or CO, the released gas molecules further enhanced hemocompatibility and promoted endothelial cell (EC) growth and the expression of vascular endothelial growth factor (VEGF) and NO of ECs. Therefore, the bioactive coatings that can catalyze the release of NO or CO have potential applications in constructing surface bioactive coatings for magnesium alloy materials used for intravascular stents.

Preparation of Time-Sequential Functionalized ZnS-ZnO Film for Modulation of Interfacial Behavior of Metals in Biological Service Environments.

Blood-contact devices are prone to inflammation, endothelial dysfunction, coagulation, and the uncontrolled release of metal ions during implantation and service. Therefore, it is essential to make these multifunctional. Herein, a superhydrophobic DE@ZnS-ZnO@SA film (composed of dabigatran ester, zinc sulfite, zinc oxide, and stearic acid, respectively) is produced. The prepared film has non-adhesion and antibacterial properties, superior mechanical stability, durability, corrosion resistance, and is self-cleaning and blood-repellent. The results of the hemolysis, cytotoxicity, and other anticoagulant experiments revealed that the film had good blood compatibility, no cytotoxicity, and excellent anticoagulant properties. The film displays anticoagulant properties even after being immersed in Phosphate-Buffered Saline (PBS) for 7 days. Furthermore, the film can spontaneously release H2S gas for 90 h after soaking in an acidic environment (pH = 6) for 90 h. This property improves the acidic microenvironment of the lesion and promotes the proliferation of endothelial cells by using H2S gas. In addition, the film can inhibit the uncontrollable release of Zn2+ ions, avoiding its toxicity even when immersed in an acid environment for 35 days. This time-sequential functionalized surface has the potential to typify the future of blood-contacting scaffolds for long-lasting use.

Sugar functionalized coumarin motifs: Synthesis and applications

Sugars are vital biomolecules widely found in nature, playing an indispensable role in a plethora of biological processes. Similarly, coumarins are heterocycles with an effective pharmacophore skeleton, making them crucial in drug design and development. Coupling carbohydrate moieties to the small biologically active molecules creates a vast library of glycoconjugates with impressive structural diversity. The potential of coumarin glycosides is being extensively explored due to their broad spectrum of applications, including antibacterial, anticancer, and anticoagulant properties, etc. This review highlights various chemical methodologies for synthesizing diverse coumarin glycohybrids with distinct linkages and explores their immense biological potential, making a significant contribution to the field of organic synthesis.

Highly selective and sustainable hemoperfusion adsorbents for effectively online cleansing bilirubin from plasma

Hemoperfusion adsorbents is of vital importance for the therapy of hyperbilirubinemia. However, developing hemoperfusion adsorbents with the satisfactory selectivity, sustainability and biocompatibility remains a global challenge. Here we proposed a novel hemoperfusion adsorbent based on molecularly imprinted polymers (MIPs) for online cleansing bilirubin. The adsorbent displayed a high specificity with the imprinting factor of 3.98. The adsorption capacity of the MIPs toward bilirubin was 135.67 mg g-1, and 86.88% of the equilibrium adsorption amounts could be reached within 3 h. The resulted MIPs could also specifically capture bilirubin from the mixed analogue molecules solutions and plasma. Compared with the clinical adsorbents, the resulted adsorbent exhibited the lower hemolysis rates (<1.35%), the higher cell viabilities (>97%) and the excellent anticoagulant property. Besides, the loss of human serum albumin and aromatic amino acid was largely reduced. Furthermore, the great stability of the adsorbent ensured its sustainable usage at least four times. These remarkable performances show the application promise for bilirubin cleansing, and this approach can easily transfer to prepare other hemoperfusion adsorbents via replacing the templates with desired targets.

Enhancing Quality of Life in Venous Ulcer Patient with Irsal-e-Alaq (Hirudotherapy): A Case Report

Background: In general practice, venous ulcers (stasis ulcers) are the most common and recurrent leg ulcers. Ignorance of it can have a severe detrimental effect on one's quality of life, cause gangrene, and even the limb amputation. Venous ulcers are the most dangerous and disabling side effect of chronic venous insufficiency. Leech therapy seems to be effective for the treatment of varicose ulcers due to its salivary secretions which it injects during bloodsucking. The saliva of leeches contains certain biochemical with vaso-dilating, anticoagulant, anesthetic, thrombolytic, antibiotic, analgesic, and anti-inflammatory properties. As a result, Irsal-e-Alaq (Hirudotherapy), one of the Unani regimens, can effectively control it. Objective: The purpose of this case report is to provide insight into the effects of Irsal-e-Alaq (Hirudotherapy) on venous ulcers. Intervention: A 60-year-old male has a complaint of ulceration in his left lower leg near the medial malleolus with swelling, pain, discharge, and darkening of the skin of the left lower limb. Four leeches were applied once every week for 2 months. Efficacy of leech therapy was assessed on every 15th day by pain /leg discomfort on 4 point scale ranging from 0-3, limb girth at calf, ankle &amp; foot, pigmentation color on 4 point scale, pigmentation area, pain in ulcer on 4 point scale from 0-3, ulcer depth, PUSH Score. Hb% was assessed every 15th day to check anemia, colour flow Doppler was done to assess any change in vein anatomy. Result: In this case report, the ulcers were completely healed, and also showed remarkable improvement in other variables. Conclusion: Irsal-e-Alaq has been proven beneficial in treating venous ulcers and enhancing patient’s quality of life. Keywords: Venous ulcer, Hirudotherapy, Unani Medicine, Pain, Pigmentation.

An Exopolysaccharide from the Cyanobacterium Arthrospira platensis May Utilize CH-π Bonding: A Review of the Isolation, Purification, and Chemical Structure of Calcium-Spirulan.

The CH-π bonding potential of a saccharide is determined primarily by the number of hydrogen atoms available for bonding and is reduced by side groups that interfere with the CH-π bond. Each hydrogen bond increases the total bond energy, while interfering hydroxyl groups and other side groups reduce the bond energy by repulsion. The disaccharide repeating units of Calcium-Spirulan (Ca-SP), a large exopolysaccharide sub fractionated from the supernatant of the cyanobacterium Arthrospira platensis, contain a unique monosaccharide that is completely devoid of hydroxyl groups and side groups on its entire beta surface, leaving five hydrogen atoms available for CH-π bonding in the planar conformation. While planar conformations of independent pyranose rings are rare-to-nonexistent, due to ring strain associated with that conformation, the binding site of a protein could provide the conformational energy needed to overcome that energy barrier. By enabling a planar conformation, a protein could also enable the sugar to form a novel 5-hydrogen CH-π bond configuration. One study of the anticoagulant property of Ca-SP shows that the molecule acts as an activator of Heparin Cofactor II (HC-II), boosting its anticoagulant kinetics by 104. In comparison, the longstanding anticoagulant drug Heparin boosts the HC-II kinetics by 103. The difference may be explained by this unique CH-π configuration. Here, we review current knowledge and experience on the isolation techniques, analytical methods, and chemical structures of Ca-SP. We emphasize a discussion of the CH-π bonding potential of this unique polysaccharide because it is a topic that has not yet been addressed. By introducing the topic of CH-π bonding to the cyanobacterial research community, this review may help to set the stage for further investigation of these unique molecules, their genetics, their biosynthetic pathways, their chemistry, and their biological functions.

Studies on in vivo antithrombotic activity of quercetin, a natural flavonoid isolated from a traditional medicinal plant, African eggplant (Solanum indicum)

Ethnopharmacological relevanceEvery year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. Aim of the studyThis study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. Materials and methodsBioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. ResultsQC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 μM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 μM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). ConclusionEffective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.

Hydrogel coating containing heparin and cyclodextrin/paclitaxel inclusion complex for retrievable vena cava filter towards high biocompatibility and easy removal

Aiming to improve the retrieval rate of retrievable vena cava filters (RVCF) and extend its dwelling time in vivo, a novel hydrogel coating loaded with 10 mg/mL heparin and 30 mg/mL cyclodextrin/paclitaxel (PTX) inclusion complex (IC) was prepared. The drug-release behavior in the phosphate buffer solution demonstrated both heparin and PTX could be sustainably released over approximately two weeks. Furthermore, it was shown that the hydrogel-coated RVCF (HRVCF) with 10 mg/mL heparin and 30 mg/mL PTX IC effectively extended the blood clotting time to above the detection limit and inhibited EA.hy926 and CCC-SMC-1 cells' proliferation in vitro compared to the commercially available bare RVCF. Both the HRVCF and the bare RVCF were implanted into the vena cava of sheep and retrieved at at 2nd and 4th week after implantation, revealing that the HRVCF had a significantly higher retrieval rate of 67 % than the bare RVCF (0 %) at 4th week. Comprehensive analyses, including histological, immunohistological, and immunofluorescent assessments of the explanted veins demonstrated the HRVCF exhibited anti-hyperplasia and anticoagulation properties in vivo, attributable to the hydrogel coating, thereby improving the retrieval rate in sheep. Consequently, the as-prepared HRVCF shows promising potential for clinical application to enhance the retrieval rates of RVCFs.

Optimizing the fucoidan extraction using Box-Behnken Design and its potential bioactivity

Fucoidan is a sulfated polysaccharide that occurs naturally in the cell wall of brown seaweeds and has substantial biological efficacy. Optimizing the extraction of fucoidan from different brown seaweeds was the primary goal of this research. The optimization of fucoidan extraction was applied on the brown macroalga Turbinaria turbinata using a Box-Behnken Design (BBD) to inspect the impacts of different pH (3, 5, 7), temperature (70, 80, 90 °C) and extraction duration (60, 120, 180 min) on both the yield and sulfate content of fucoidan. The optimized parameters recorded to maximize the fucoidan yield and its sulfate content were a pH of 3.44 and a temperature of 82.26 °C for 60 min. The optimal conditions obtained from BBD were used for fucoidan extraction from T. turbinata, Sargassum cinereum, Padina pavonica, and Dictyota dichotoma. The highest average of fucoidan yield was derived from P. pavonica (40.76 ± 4.04 % DW). FTIR, 1H NMR, and HPLC were used to characterize extracted fucoidan. The extracted fucoidan's Physical characteristics, biochemical composition, antioxidant potential, antitumor effect against breast cancer cells (MCF-7), and antimicrobial and anticoagulant activity were assessed. The extracted fucoidan from D. dichotoma, followed by that extracted from S. cinereum, which had the highest sulphate content, depicted the highest antioxidant, anticancer, and anticoagulant activities. Fucoidan has demonstrated a strong antimicrobial action against some pathogenic microorganisms; Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Candida albicans. The anticoagulant properties of fucoidan from D. dichotoma were stronger than those of fucoidan from S. cinereum, T. turbinata, and P. pavonica due to its higher sulphate content. These findings could be used for various biomedical applications to improve the pharmaceutical industry.

An endothelium membrane mimetic antithrombotic coating enables safer and longer extracorporeal membrane oxygenation application

Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. Statement of significanceA superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.

Epigenetic Targeting of Heparan Sulfate 3-O- and 6-O-Sulfation in Breast Cancer Cells: Prospects for Attenuating Prothrombotic Tumor Cell Activities.

The deregulation of cell surface heparan sulfate proteoglycans (HSPGs) is a main issue of cancer cells for increasing their malignancy. In these terms, the sulfation pattern of HS, created by an orchestrated activity of enzymes balancing a site-specific sulfation, is of key importance. These enzymes are often deregulated by epigenetic processes in cancer, e.g., being silenced by DNA hypermethylation. Here, we address this issue in human breast cancer cell lines aiming to target epigenetic processes to reactivate HS sulfation, shifting HS into an antithrombotic phenotype for which 3-O-sulfation is particularly important. Treatment of MCF-7 and MDA-MB-231 cells with nontoxic concentrations of 5-azacytidine (azacytidine) and 5-fluoro-2'-deoxycytidine (FdCyd) as DNMT inhibitors or vorinostat for targeting HDAC increased HS3-O-sulfation remarkably, as confirmed by fluorescence microscopy, by upregulating HS3-O-sulfotransferases, detected by quantitative real-time polymerase chain reaction and Western blot. Flow cytometry and microscopic approaches confirm that upon inhibitor treatment, increased HS3-O-sulfation improves cell binding to antithrombin, leading to an antithrombotic activity. Nevertheless, only azacytidine- and vorinostat-treated cells display anticoagulative properties, represented by attenuated thrombin formation, a lower activation of human platelet aggregation, or ATP release. In contrast, FdCyd additionally upregulated tissue factor expression in both cell lines, overshadowing the anticoagulant effects of HS, leading to an overall prothrombotic phenotype. Our data provide evidence for the first time that targeting epigenetic processes in HS sulfation is a valuable means to foster anticoagulative cell properties for decreasing malignancy and metastatic potency. These data warrant further investigations to fine-tune epigenetic targeting and to search for potential biomarkers attributed to these activities.

Anticoagulant Protective Effects of Sulfated Chitosan Derived From the Internal Bone of Spineless Cuttlefish (Sepiella inermis).

Background This study investigated the anticoagulant properties of sulfated chitosan derived from the internal bone of the spineless cuttlefish Sepiella inermis. Chitosan, a biopolymer, is used in various biomedical applications including anticoagulation. Sulfation of chitosan enhances its biological activity, making it a potential therapeutic agent. This study explored the efficacy of sulfated chitosan in preventing blood clot formation to provide a novel anticoagulant alternative. Objectives This study aimed to synthesize and characterize the anticoagulant properties of sulfated chitosan extracted from the internal bone of the spineless cuttlefish S. inermis using Fourier Transform Infrared Spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), and X-Ray Diffraction (XRD) and evaluate the anticoagulant properties of sulfated chitosan extracted from the internal bone of spineless cuttlefish S. inermis. Materials and methods Chitin and chitosan were extracted from the cuttlebone of a specimen of S. inermis, and sulfated chitosan was synthesized by sulfation of chitosan. Sulfated chitosan was subsequently used to evaluate its anticoagulant properties using tests such as activated partial thromboplastin time (APTT) and prothrombin time (PT). Characteristic investigations were conducted, including FTIR, FESEM, and XRD analyses. Results The results of this study suggested the possibility of using S. inermis internal bone as an unconventional source of natural anticoagulant that can be combined with biomedical applications. Anticoagulant activity measured using APTT and PT showed that sulfated chitosan was a strong anticoagulant. Conclusion We examined the anticoagulant activity of S. inermis extract using thrombin and activated partial thromboplastin times. Our results demonstrated the heparin-like anticoagulant action of the extracted sulfated chitosan, suggesting that it may be a great alternative anticoagulant treatment.

Phytochemistry and Biological Profile of the Chinese Endemic Herb Genus Notopterygium.

Notopterygium, a plant genus belonging to the Apiaceae family, is utilized in traditional Chinese medicine for its medicinal properties. Specifically, the roots and rhizomes of these plants are employed in phytotherapy to alleviate inflammatory conditions and headaches. This review provides a concise overview of the existing information regarding the botanical description, phytochemistry, pharmacology, and molecular mechanisms of the two Notopterygium species: Notopterygium incisum and N. franchetii. More than 500 distinct compounds have been derived from these plants, with the root being the primary source. These components include volatile oils, coumarins, enynes, sesquiterpenes, organic acids and esters, flavonoids, and various other compounds. Research suggests that Notopterygium incisum and N. franchetii exhibit a diverse array of pharmacological effects, encompassing antipyretic, analgesic, anti-inflammatory, antiarrhythmic, anticoagulant, antibacterial, antioxidant, and anticancer properties on various organs such as the brain, heart, digestive system, and respiratory system. Building activity screening models based on the pharmacological effects of Notopterygium species, as well as discovering and studying the pharmacological mechanisms of novel active ingredients, will constitute the primary development focus of Notopterygium medicinal research in the future.

Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review.

This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G-90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing invitro and invivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well-developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in invitro and invivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Chemical approaches to the sulfation of small molecules: current progress and future directions.

Sulfation is one of the most important modifications that occur to a wide range of bioactive small molecules including polysaccharides, proteins, flavonoids, and steroids. In turn, these sulfated molecules have significant biological and pharmacological roles in diverse processes including cell signalling, modulation of immune and inflammation response, anti-coagulation, anti-atherosclerosis, and anti-adhesive properties. This Essay summarises the most encountered chemical sulfation methods of small molecules. Sulfation reactions using sulfur trioxide amine/amide complexes are the most used method for alcohol and phenol groups in carbohydrates, steroids, proteins, and related scaffolds. Despite the effectiveness of these methods, they suffer from issues including multiple-purification steps, toxicity issues (e.g., pyridine contamination), purification challenges, stoichiometric excess of reagents which leads to an increase in reaction cost, and intrinsic stability issues of both the reagent and product. Recent advances including SuFEx, the in situ reagent approach, and TBSAB show the widespread appeal of novel sulfating approaches that will enable a larger exploration of the field in the years to come by simplifying the purification and isolation process to access bespoke sulfated small molecules.