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Protein extract of kenaf seed exhibits anticoagulant,antiplatelet and antioxidant activities

Asian Pacific Journal of Tropical Biomedicine 2022年第2期12卷 47-58页

作者： Sujatha M.Hanumegowda Chandramma Srinivasa Ashwini Shivaiah Manjula M.Venkatappa Ramesha Hanumanthappa Rajesh Rangappa Ramesh K.Laxmaiah Sathisha J.Gonchigar Devaraja Sannaningaiah Department of Biochemistry Jnansahydri Kuvempu UniversityShankarghatta-577451ShivamoggaKarnatakaIndia Department of Studies and Research in Biochemistry and Centre for Bioscience and Innovation Tumkur UniversityTumkurKarnatakaIndia Liveon Biolabs Private Limited Tumkur-572106India Department of Food Science and Nutrition Maharani's Science College for WomenMysoreIndia

Objective:To explore the anticoagulant,antiplatelet and antioxidant activities of protein extract of kenaf seed(PEKS).Methods:Sodium dodecyl sulphate polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography techniques were employed for protein characterization.Antioxidant activity of PEKS was assessed using 1,1-diphenyl-2-picrylhydrazyl(DPPH)assay.The protective effect of PEKS on sodium nitrite(NaNO2)induced oxidative stress was evaluated using the in vitro red blood cell model,while the effect of PEKS on diclofenacinduced oxidative stress was examined in vivo in rats.Platelet-rich plasma and platelet-poor plasma were used for anticoagulant and antiplatelet activities of PEKS.Results:PEKS revealed similar protein bands on SDS-PAGE under reduced and non-reduced conditions.Several acidic proteins were present in native PAGE.PEKS showed antioxidant properties by scavenging DPPH with an IC50 of 24.58μg.PEKS exhibited a protective effect on NaNO2 induced oxidative stress in red blood cells by restoring the activity of stress markers.In addition,PEKS alleviated diclofenac-induced tissue damage of the liver,kidney,and small intestine.PEKS showed an anticoagulant effect in both in vivo and in vitro experiments by enhancing normal clotting time.PEKS did not affect prothrombin time but increase activated partial thromboplastin time.Furthermore,PEKS inhibited adenosine diphosphate and epinephrine-induced platelet aggregation.Conclusions:PEKS protects tissues from oxidative stress and exhibits antithrombotic activity.

关键词： Protein Extract Kenaf seed Oxidative stress Antioxidant anticoagulant Antiplatelet

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Current practice of anticoagulant in the treatment of splanchnic vein thrombosis secondary to acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 116-121页

作者： William Norton Gabija Lazaraviciute George Ramsay Irene Kreis Irfan Ahmed Mohamed Bekheit Department of General Surgery Aberdeen Royal InfirmaryAberdeen AB252ZNUK Rowett Institute of Nutrition and Health University of AberdeenForesterhillAberdeen AB252ZDUK Clinical Effectiveness Unit Royal College of Surgeons of England35-43 Lincoln’s Inn FieldsHolbornLondon WC2A 3PEUK Department of Surgery El Kabbary HospitalEl KabbaryAlexandriaEgypt

Background:Severe acute pancreatitis is a common diagnosis in emergency general surgery and can be a cause of significant morbidity and mortality.A consequence of severe acute pancreatitis is thrombus in the splanchnic veins.These thrombi can potentially lead to bowel ischemia or hepatic failure.However,another complication of severe acute pancreatitis is retroperitoneal bleeding.At this time,it is unclear if treating patients for splanchnic vein thrombosis in the context of severe acute pancreatitis is associated with any outcome benefit.A systematic review might clarify this question.Data sources:A two-fold search strategy(one broad and one precise)looked at all published literature.The review was registered on PROSPERO(ID:CRD42018102705).MEDLINE,EMBASE,PubMed,Cochrane and Web of Science databases were searched and potentially relevant papers were reviewed indepen-dently by two researchers.Any disagreement was reviewed by a third independent researcher.Primary outcome was reestablishment of flow in the thrombosed vein versus bleeding complications.Results:Of 1462 papers assessed,a total of 16 papers were eligible for inclusion.There were no ran-domized controlled trials,2 were case series,5 retrospective single-center studies and 9 case reports.There were a total of 198 patients in these studies of whom 92(46.5%)received anticoagulation therapy.The rates of recanalization of veins in the treated and non-treated groups was 14%and 11%and bleeding complications were 16%and 5%,respectively.However,the included studies were too heterogeneous to undertake a meta-analysis.Conclusions:The systematic review highlights the lack evidence addressing this clinical question.There-fore a randomized controlled trial would be appropriate to undertake.

关键词： Severe acute pancreatitis Splanchnic vein thrombosis anticoagulant therapy

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Rate of anticoagulant use, and factors associated with not prescribing anticoagulant in older Thai adults with non-valvular atrial fibrillation: A multicenter registry

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Journal of Geriatric Cardiology 2019年第3期16卷 242-250页

作者： Rungroj Krittayaphong Arintaya Phrommintikul Pornchai Ngamjanyaporn Khanchai Siriwattana Wiwat Kanjanarutjawiwat Thoranis Chantrarat Roj Rojjarekampai Pontawee Kaewcomdee Patthrapon Sonkhammee Division of Cardiology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand Faculty of Medicine Chiang Mai UniversityChiang MaiThailand Chonburi Hospital ChonburiThailand Nakornping Hospital Chiang MaiThailand Prapokklao Hospital ChanthaburiThailand Phramongkutklao College of Medicine Mahidol UniversityBangkokThailand Faculty of Medicine Thammasat UniversityPathum ThaniThailand

Objectives To investigate the rate of anticoagulant use,the reasons for not prescribing anticoagulant,and the factors associated with non-prescription of anticoagulant in older Thai adults with non-valvular atrial fibrillation.Methods A multicenter registry of patients with non-valvular atrial fibrillation was conducted during 2014 to 2017 in Thailand.Demographic,medical history,antithrombotic medication,non-antithrombotic medication,and laboratory data were collected and analyzed.Data were compared between the older adult (≥ 65 years) and younger adult (anticoagulant was not prescribed were collected,and predictive factors were identified.Results A total of 3218 patients (1873 males) with an average age of 67.3 ± 11.3 years were included.Almost two-thirds (61.0%) of patients were in the older adult group.anticoagulant was prescribed in 2422 patients (75.3%): 81.4% in the older adult group and 65.7% in the younger adult group.The three main reasons for not prescribing anticoagulant were already taking antiplatelets,patient refusal,and bleeding risk.These reasons were more common in older adults as compared to younger adults.Multivariate analysis revealed current use of antiplatelets to be the most important factor that predict the non-prescription of anticoagulant in older population.Conclusions The prevalence of anticoagulant prescription among older Thai adults with atrial fibrillation is 81.4%.Taking antiplatelet drugs was found to be the strongest reason that predicts the non-prescription of anticoagulant in this patient population.A guideline should be developed to optimize the use of anticoagulant and antiplatelet in older adults.

关键词： anticoagulant use Multicenter registry Non-valvular atrial fibrillation Older Thai adults

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Current status of anticoagulant treatments and improvements for hemodialysis patients in northern Chinese cities： a five-year comparative study

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Chinese Medical Journal 2014年第16期127卷 2881-2887页

作者： Huang Qi Sun Xuefeng Lin Hongli Zhang Zhimin Hao Lirong Yao Li Li Jijun Zhao Delong Wang Yong Zhu Hanyu Chen Xiangmei Department of Nephrology Chinese People's Liberation Army General Hospital Chinese People's Liberation Army Institute of Nephrology State Key Laboratory of Kidney Disease(2011DAV00088) National Clinical Research Center of Kidney Diseases(2013BAI09B05)Beijing 100853 China Department of Nephrology First Affiliated Hospital Dalian Medical College Dalian Liaoning 116023 China Department of Nephrology General Hospital of the General Headquarters Beijing 100091 China Department of Nephrology First Affiliated Hospital Harbin Medical College Harbin Heilongjiang 150081 China Department of Nephrology First Affiliated Hospital Chinese Medical University Shenyang Liaoning 110001 China Department of Nephrology First Affiliated Hospital General Hospital of People's Liberation Army Beijing 100048 China

Background Anticoagulation treatments are an important aspect of hemodialysis; however,few reports have addressed these treatments.This investigation intends to increase the understanding of the current status and improvements of hemodialysis-related anticoagulation treatments in China.Methods In this study,an epidemiological investigation was conducted that examined 842 patients in 2007 and 1 175patients in 2012 who underwent hemodialysis anticoagulation treatments in seven blood purification centers in northern Chinese cities.Results Heparin was the most commonly used anticoagulant,although the percentage of use of low-molecular-weight heparin （LMWH） increased from 26.5% in 2007 to 42.1% in 2012.In 2007,there were no significant differences in anticoagulant selection among either patients with various primary diseases or patients with hemorrhage,thrombosis,thrombocytopenia,or a low hemoglobin level.However,compared with patients with other diseases,significantly lower doses of LMWH were administered to patients with hypertension （55.5 U/kg vs.67.3 U/kg,P 〈0.05） or diabetes （58.5 U/kg vs.67.3 U/kg,P 〈0.05）,and patients with hemorrhage received lower doses of heparin than the other patients （61.6 U/kg vs.71.8 U/kg,P 〈0.01）.In 2012,patients with diabetic nephropathy （51.5% vs.36.5%,P 〈0.01）,hemorrhage （43.4% vs.31.7%,P 〈0.01）,or a hemoglobin level below 90 g/L （57.2% vs.37.1%,P 〈0.01） experienced significantly higher doses of LMWH administration; patients with hemorrhage received significantly reduced LMWH dosages （50.4 U/kg vs.57.8 U/kg,P 〈0.05）,and patients with thrombosis received significantly higher doses of heparin （73.8 U/kg vs.62.1 U/kg,P 〈0.01） or LMWH （57.8 U/kg vs.52.6 U/kg,P 〈0.05）.Antiplatelet drugs were administered to 20.4% of the examined patients in 2007 and 20.7% in 2012.In 2012,patients with hypertension （25.9% vs.18.5%,P 〈0.01） and thrombosis （36.6% vs.16.1%,P 〈0.01） had a higher rate of using antiplatelet drugs than patients with other primary diseases and complications.Patients receiving anti

关键词： hemodialysis heparin low-molecular-weight heparin anticoagulant

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Quantitation of bivalirudin,a novel anticoagulant peptide,in human plasma by LC-MS/MS:Method development,validation and application to pharmacokinetics

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Journal of Pharmaceutical Analysis 2013年第1期3卷 1-8页

作者： Xiao-Jiao Li Yan-Tong Sun Lei Yin Xue-Ju Zhang Yan Yang J.Paul Fawcett Yi-Min Cui Jing-Kai Gu Clinical Pharmacology Center Research Institute of Translational MedicineThe First Bethune Hospital of Jilin University Research Center for Drug Metabolism College of Life ScienceJilin University School of Pharmacy University of Otago Department of Pharmacy Peking University First Hospital

A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichloromethane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 column （150 mm x 4.6 mm i.d., 5 gm particle size） using 0.1% formic acid：methanol （45：55, v/v） as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization （ESI） interface, was operated in the positive ion mode, and the multiplereaction monitoring （MRM） transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5 - 249.3, respectively. The lower limit of quantification （LLOQ） was 1 ng/mL for 100 ng/mL plasma sample and the assay was linear over the concentration range 1 1000 ng/mL. The accuracy was within a range from -0.4% to 0.5% in terms of relative error （RE） and the intra- and inter-day precisions in terms of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin （0.5 mg/kg） to Chinese volunteers.

关键词： Bivalirudin LC-MS/MS Pharmacokinetics Human plasma anticoagulant

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Synthesis and anticoagulant Bioactivity Evaluation of 1,2,5-Trisubstituted BenzimidazoleFluorinated Derivatives

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Chemical Research in Chinese Universities 2016年第6期32卷 973-978页

作者： Haoran Yang Yujie Ren Xiaodong Gao Yonghong Gao College of Chemical and Environmental Engineering Shanghai Institute of Technology Shanghai P. R. China

Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by moleculardocking. Five compounds which obtained high scores were selected to synthesize. All the target products were cha-racterized by 1H NMR, 13C NMR and high resolution mass spectra（HRMS） and preliminarily screened for inhibitoryactivity against thrombin, among which three compounds（5a, 5c and 5e） were evaluated in vitro. The results showedthat compounds 5a, 5c and 5e exhibited better anticoagulant activity than argatroban. Docking simulations demon-strated that these compoands may act as candidates for further studies on thrombin inhibitors.

关键词： Benzimidazole derivative Fluorine anticoagulant bioactivity Molecular docking

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Polyguluronate Sulfate,Polymannuronate Sulfate,and Their Oligosaccharides Have AntithrombinⅢ-and Heparin CofactorⅡ-independent anticoagulant Activity

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Journal of Ocean University of China 2017年第2期16卷 346-350页

作者： ZENG Xuan LAN Ying ZENG Pengjiao GUO Zhihua HAO Cui ZHANG Lijuan School of Medicine and Pharmacy Ocean University of ChinaQingdao 266003P.R.China Institute of Cerebrovascular Diseases Affiliated Hospital of Qingdao UniversityQingdao 266003P.R.China

Cardiovascular disease is the leading causes of death.However,the complications can be treated with heparin and heparinoids,such as heparin pentasaccharide Fondaparinux,dermatan sulfate,and PSS made from alginate extracted from brown seaweeds by chemical sulfation.Alginate is composed of a linear backbone of polymannuronate(PM),polyguluronate(PG),and alternate residues of mannuronic acid and guluronic acid.It is unknown if heparin and sulfated PG(PGS)/PM(PMS) have the same or different anticoagulant molecular targets.In the current study,the anticoagulant activities of PGS,PMS,and their oligosaccharides were directly compared to that of heparin,Fondaparinux,and dermatan sulfate by the activated partial thrombinplastin time(aP TT) assay using normal,antithrombin III(ATIII)-deficient,heparin co-factor II(HCII)-deficient,and ATIII-and HCII-double deficient human plasmas.Our results showed that PGS,PMS,and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested.As expected,heparin was the best anticoagulant in normal plasma.Moreover,PGS,PGS6,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma.Most strikingly,PGS,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than that of heparin in ATIII-and HCII-double deficient human plasma.The results revealed for the first time that sulfated alginate had ATIII-and HCII-independent anticoagulant activities.Therefore,developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.

关键词： anticoagulant polyguluronate sulfate polygmannuronate sulfate heparin, Fondaparinux dermatan sulfate

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Frailty and anticoagulant Therapy in Patients Aged 65 Years or Older with Atrial Fibrillation

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Cardiovascular Innovations and Applications 2020年第1期4卷 153-161页

作者： Jiapeng Liu Xin Du Mengmeng Li Zhaoxu Jia Shangxin Lu Sanshuai Chang Ribo Tang Rong Bai Jianzeng Dong Gregory Y.H.Lip Changsheng Ma Department of Cardiology Beijing Anzhen HospitalCapital Medical University and National Clinical Research Center for Cardiovascular DiseasesBeijingChina Heart Health Research Center BeijingChina University of New South Wales SydneyAustralia Department of Cardiology The First Affi liated Hospital of Zhengzhou UniversityZhengzhouChina Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart and Chest HospitalLiverpoolUK Aalborg Thrombosis Research Unit Department of Clinical MedicineAalborg UniversityAalborgDenmark

Background:Elderly adults with atrial fi brillation(AF)are at increased risk of frailty and thromboembolic complications.However,studies on the prevalence of frailty in AF patients and data on the relationship between frailty and the use of anticoagulants are limited.Methods:We conducted a cross-sectional study involving 500 participants.Patients aged 65 years or older were consecutively selected from the Chinese Atrial Fibrillation Registry study.The patient’s frailty status was assessed with use of the Canadian Study of Health and Aging Clinical Frailty Scale.We assessed the prevalence of and factors associated with frailty,and how frailty affects anticoagulant therapy.Results:In 500 elderly adults with AF(age 75.2±6.7 years;51.6%female),201 patients(40.2%)were frail.The prevalence of frailty was higher in females(P=0.002)and increased with age and CHA 2 DS 2-VASc score(P for trend less than 0.001 for both).The factors associated with frailty were a history of heart failure(odds ratio[OR]2.40,95%confi dence interval[CI]1.39–4.14),female sex(OR 2.09,95%CI 1.27–3.43),and advanced age(OR 1.13,95%CI 1.09–1.17).Frail patients were signifi cantly less likely to have ever been prescribed anticoagulants compared with nonfrail patients(81.7 vs.54.9%,Panticoagulants for high-risk AF patients.

关键词： atrial fi brillation frailty anticoagulant elderly adults

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A breakthrough trial of an artificial liver without systemic heparinization in hyperbilirubinemia beagle models

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Bioactive Materials 2023年第2期20卷 651-662页

作者： Yilin Wang Shanshan Wang Xueqin He Yupei Li Tao Xu Lin Xu Bo Yang Xinnian Fan Weifeng Zhao Changsheng Zhao College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu610065China Med-X Center for Materials Sichuan UniversityChengdu610041China Department of Nephrology West China HospitalSichuan UniversityChengdu610041China

The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants.Herein,a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres(KPMs,bilirubin adsorbents)was connected with the principle machine of wearable artificial liver(approximately 9 kg)to treat hyperbilirubinemia beagles for the first time.With the initial normal dose of heparin,the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation.The removal efficiency of the double-deck column for total bilirubin(TBIL)was 31.4%.Interestingly,the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%.The“anticoagulant+column”realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump;however,the proposed principle machine of wearable artificial liver and“anticoagulant+column”cannot completely replace the bio-liver now.The intelligence of the device and the versatility of the adsorbent need to be improved;moreover,advanced experimental techniques need to be developed to validate the survival rates in animals.Overall,this study is a meaningful trial for the development of wearable artificial livers in the future.

关键词： Wearable artificial liver anticoagulant Bilirubin Kevlar Microspheres

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Atrial fibrillation:mechanism and clinical management

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Chinese Medical Journal 2023年第22期136卷 2668-2676页

作者： Zhicheng Hu Ligang Ding Yan Yao Cardiac Arrhythmia Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Atrial fibrillation(AF),the most common sustained arrhythmia,is associated with a range of symptoms,including palpitations,cognitive impairment,systemic embolism,and increased mortality.It places a significant burden on healthcare systems worldwide.Despite decades of research,the precise mechanisms underlying AF remain elusive.Current understanding suggests that factors like stretch-induced fibrosis,epicardial adipose tissue(EAT),chronic inflammation,autonomic nervous system(ANS)imbalances,and genetic mutations all play significant roles in its development.In recent years,the advent of wearable devices has revolutionized AF diagnosis,enabling timely detection and monitoring.However,balancing early diagnosis with efficient resource utilization presents new challenges for healthcare providers.AF management primarily focuses on stroke prevention and symptom alleviation.Patients at high risk of thromboembolism require anticoagulation therapy,and emerging pipeline drugs,particularly factor XI inhibitors,hold promise for achieving effective anticoagulation with reduced bleeding risks.The scope of indications for catheter ablation in AF has expanded significantly.Pulsed field ablation,as a novel energy source,shows potential for improving success rates while ensuring safety.This review integrates existing knowledge and ongoing research on AF pathophysiology and clinical management,with emphasis on diagnostic devices,next-generation anticoagulants,drugs targeting underlying mechanisms,and interventional therapies.It offers a comprehensive mosaic of AF,providing insights into its complexities.

关键词： Atrial fibrillation Pathophysiology Clinical management Wearable device anticoagulant

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