scholarly journals Carboxypeptidase U (CPU, TAFIa, CPB2) in Thromboembolic Disease: What Do We Know Three Decades after Its Discovery?

2021 ◽  
Vol 22 (2) ◽  
pp. 883
Author(s):  
Karen Claesen ◽  
Joachim C. Mertens ◽  
Dorien Leenaerts ◽  
Dirk Hendriks
Keyword(s):  
Risk Factors ◽  
Thrombolytic Therapy ◽  
Potential Benefit ◽  
Current Knowledge ◽  
Thromboembolic Disease ◽  
Thromboembolic Risk ◽  
Endogenous Fibrinolysis ◽  
Coagulation And Fibrinolysis

Procarboxypeptidase U (proCPU, TAFI, proCPB2) is a basic carboxypeptidase zymogen that is converted by thrombin(-thrombomodulin) or plasmin into the active carboxypeptidase U (CPU, TAFIa, CPB2), a potent attenuator of fibrinolysis. As CPU forms a molecular link between coagulation and fibrinolysis, the development of CPU inhibitors as profibrinolytic agents constitutes an attractive new concept to improve endogenous fibrinolysis or to increase the efficacy of thrombolytic therapy in thromboembolic diseases. Furthermore, extensive research has been conducted on the in vivo role of CPU in (the acute phase of) thromboembolic disease, as well as on the hypothesis that high proCPU levels and the Thr/Ile325 polymorphism may cause a thrombotic predisposition. In this paper, an overview is given of the methods available for measuring proCPU, CPU, and inactivated CPU (CPUi), together with a summary of the clinical data generated so far, ranging from the current knowledge on proCPU concentrations and polymorphisms as potential thromboembolic risk factors to the positioning of different CPU forms (proCPU, CPU, and CPUi) as diagnostic markers for thromboembolic disease, and the potential benefit of pharmacological inhibition of the CPU pathway.

scholarly journals Review: The endless nutritional and pharmaceutical benefits of the Himalayan gold, Cordyceps; Current knowledge and prospective potentials

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Waill Elkhateeb ◽  
Ghoson Daba
Keyword(s):  
Current Knowledge ◽  
Health Benefits ◽  
Chemical Compounds ◽  
Food Supplement ◽  
In Vivo Studies ◽  
Protective Agent ◽  
Global Marketplace

Abstract. Elkhateeb WA, Daba GM. 2020. Review: The endless nutritional and pharmaceutical benefits of the Himalayan gold, Cordyceps; Current knowledge and prospective potentials. Biofarmasi J Nat Prod Biochem 18: 70-77. As a traditional medicine, Cordyceps has long been used in Asian nations for maintaining vivacity and boosting immunity. Numerous publications on various bioactivities of Cordyceps have been investigated in both in-vitro as well as in vivo studies. Nevertheless, the role of Cordyceps is still arguable whether it acts as food supplement for health benefits or a real healing drug that can be prescribed in medicine. The Cordyceps industry has developed greatly and offers thousands of products, commonly available in a global marketplace. In this review, focus will be on introducing the ecology of Cordyceps and their classification. Moreover, elucidation of the richness of extracts originated from this mushroom in nutritional components was presented, with description of the chemical compounds of Cordyceps and its well-known compounds such as cordycepin, and cordycepic acid. Furthermore, highlights on natural growth and artificial cultivation of famous Cordyceps species were presented. The health benefits and reported bioactivities of Cordyceps species as promising antimicrobial, anticancer, hypocholesterolemic, antioxidant, antiviral, anti-inflammatory, organ protective agent, and enhancer for organ function were presented.

scholarly journals HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. F1-F17
Author(s):  
Rocío Martínez-Aguilar ◽  
Lucy E Kershaw ◽  
Jane J Reavey ◽  
Hilary O D Critchley ◽  
Jacqueline A Maybin
Keyword(s):  
Current Knowledge ◽  
Abnormal Uterine Bleeding ◽  
Future Research ◽  
Hypoxic Episode ◽  
Optimal Function ◽  
Pros And Cons ◽  
The Impact ◽  
Review Current

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.

scholarly journals The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yilu Zhou ◽  
Weimin Tao ◽  
Fuyi Shen ◽  
Weijia Du ◽  
Zhendong Xu ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Neutrophil Extracellular Traps ◽  
Vital Role ◽  
Extracellular Traps ◽  
Protein Components ◽  
Cancer Associated Thrombosis ◽  
Coagulation Pathway

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

Lung epithelial NOX/DUOX and respiratory virus infections

2014 ◽  
Vol 128 (6) ◽  
pp. 337-347 ◽  
Author(s):  
Nathalie Grandvaux ◽  
Mélissa Mariani ◽  
Karin Fink
Keyword(s):  
Respiratory Virus ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Conditional Knockout ◽  
In Vivo Studies ◽  
Virus Infections ◽  
Lung Epithelial ◽  
Respiratory Virus Infections

Determining the role of NADPH oxidases in the context of virus infection is an emerging area of research and our knowledge is still sparse. The expression of various isoforms of NOX/DUOX (NADPH oxidase/dual oxidase) in the epithelial cells (ECs) lining the respiratory tract renders them primary sites from which to orchestrate the host defence against respiratory viruses. Accumulating evidence reveals distinct facets of the involvement of NOX/DUOX in host antiviral and pro-inflammatory responses and in the control of the epithelial barrier integrity, with individual isoforms mediating co-operative, but surprisingly also opposing, functions. Although in vivo studies in mice are in line with some of these observations, a complete understanding of the specific functions of epithelial NOX/DUOX awaits lung epithelial-specific conditional knockout mice. The goal of the present review is to summarize our current knowledge of the role of individual NOX/DUOX isoforms expressed in the lung epithelium in the context of respiratory virus infections so as to highlight potential opportunities for therapeutic intervention.

scholarly journals Manifestations and clinical impact of pediatric inherited thrombophilia

Blood ◽  
2015 ◽  
Vol 125 (7) ◽  
pp. 1073-1077 ◽  
Author(s):  
Irene L. M. Klaassen ◽  
C. Heleen van Ommen ◽  
Saskia Middeldorp
Keyword(s):  
Risk Factors ◽  
Clinical Impact ◽  
Thromboembolic Disease ◽  
Clinical Risk Factors ◽  
Venous Thromboembolic Disease ◽  
Inherited Thrombophilia ◽  
Clinical Risk ◽  
Venous Thromboembolic ◽  
Thrombophilia Testing

Abstract The etiology of pediatric venous thromboembolic disease (VTE) is multifactorial, and in most children, 1 or more clinical risk factors are present. In addition, inherited thrombophilic disorders contribute to the development of pediatric VTE. In this review, the role of inherited thrombophilic disorders in the development of pediatric VTE, as well as the benefits and limitations of thrombophilia testing, will be discussed.

scholarly journals Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Wai Y. Sun ◽  
Claudine S. Bonder
Keyword(s):  
Current Knowledge ◽  
Financial Burden ◽  
Late Phase ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Racial Groups ◽  
Worldwide Population ◽  
Life Threatening

Allergic inflammation is an immune response to foreign antigens, which begins within minutes of exposure to the allergen followed by a late phase leading to chronic inflammation. Prolonged allergic inflammation manifests in diseases such as urticaria and rhino-conjunctivitis, as well as chronic asthma and life-threatening anaphylaxis. The prevalence of allergic diseases is profound with 25% of the worldwide population affected and a rising trend across all ages, gender, and racial groups. The identification and avoidance of allergens can manage this disease, but this is not always possible with triggers being common foods, prevalent air-borne particles and only extremely low levels of allergen exposure required for sensitization. Patients who are sensitive to multiple allergens require prophylactic and symptomatic treatments. Current treatments are often suboptimal and associated with adverse effects, such as the interruption of cognition, sleep cycles, and endocrine homeostasis, all of which affect quality of life and are a financial burden to society. Clearly, a better therapeutic approach for allergic diseases is required. Herein, we review the current knowledge of allergic inflammation and discuss the role of sphingolipids as potential targets to regulate inflammatory development in vivo and in humans. We also discuss the benefits and risks of using sphingolipid inhibitors.

scholarly journals A Review of Vascular Disease Risk Factors and Multiple Sclerosis

US Neurology ◽  
2017 ◽  
Vol 13 (02) ◽  
pp. 90
Author(s):  
Meena R Kannan ◽  
Vijayshree Yadav ◽  
◽  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Vascular Disease ◽  
Type Ii Diabetes ◽  
Demyelinating Disease ◽  
Disease Risk ◽  
Current Knowledge ◽  
Type Ii Diabetes Mellitus ◽  
The Central Nervous System

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common non-traumatic cause of disability in young adults. Recent research shows that vascular disease risk factors (VDRFs) such as obesity, smoking, hyperlipidemia, hypertension, type II diabetes mellitus, and metabolic syndrome, can influence MS on its onset, disease activity, progression, and resultant disability. This review evaluates the current knowledge on the role of VDRFs on outcomes among people with MS (PwMS) and shows that while VDRF prevalence may or may not be higher among PwMS compared with the general population, its presence can influence MS in myriad ways. Management of VDRFs through early detection and treatment may be a promising approach to improving outcomes in PwMS.

scholarly journals The biology of cutaneous neurofibromas

Neurology ◽  
2018 ◽  
Vol 91 (2 Supplement 1) ◽  
pp. S14-S20 ◽  
Author(s):  
Jean-Philippe Brosseau ◽  
Dominique C. Pichard ◽  
Eric H. Legius ◽  
Pierre Wolkenstein ◽  
Robert M. Lavker ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Research Priorities ◽  
Future Research ◽  
In Vivo Models ◽  
Cells Of Origin ◽  
Group Members ◽  
Multiple Levels

ObjectiveA group of experts in dermatology, genetics, neuroscience, and regenerative medicine collaborated to summarize current knowledge on the defined factors contributing to cutaneous neurofibroma (cNF) development and to provide consensus recommendations for future research priorities to gain an improved understanding of the biology of cNF.MethodsThe group members reviewed published and unpublished data on cNF and related diseases via literature search, defined a set of key topic areas deemed critical in cNF pathogenesis, and developed recommendations in a series of consensus meetings.ResultsFive specific topic areas were identified as being relevant to providing an enhanced understanding of the biology of cNF: (1) defining the human cells of origin; (2) understanding the role of the microenvironment, focusing on neurons, mast cells, and fibroblasts; (3) defining the genetic and molecular differences between the cNFs, focusing on size and number; (4) understanding if sex hormones are critical for cNF development or progression; and (5) identifying challenges in establishing in vitro and in vivo models representing human cNF.ConclusionsThe complexity of cNF biology stems from its heterogeneity at multiple levels including genetic, spatial involvement, temporal development, and cellular composition. We propose a unified working model for cNF that builds a framework to address the key questions about cNF that, when answered, will provide the necessary understanding of cNF biology to allow meaningful development of therapies.

scholarly journals Targeting Platelet in Atherosclerosis Plaque Formation: Current Knowledge and Future Perspectives

2020 ◽  
Vol 21 (24) ◽  
pp. 9760
Author(s):  
Lei Wang ◽  
Chaojun Tang
Keyword(s):  
Risk Factors ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Current Knowledge ◽  
Vascular Inflammation ◽  
Plaque Formation ◽  
Inflammatory Factors ◽  
Future Perspectives ◽  
Atherosclerotic Plaque Formation

Besides their role in hemostasis and thrombosis, it has become increasingly clear that platelets are also involved in many other pathological processes of the vascular system, such as atherosclerotic plaque formation. Atherosclerosis is a chronic vascular inflammatory disease, which preferentially develops at sites under disturbed blood flow with low speeds and chaotic directions. Hyperglycemia, hyperlipidemia, and hypertension are all risk factors for atherosclerosis. When the vascular microenvironment changes, platelets can respond quickly to interact with endothelial cells and leukocytes, participating in atherosclerosis. This review discusses the important roles of platelets in the plaque formation under pro-atherogenic factors. Specifically, we discussed the platelet behaviors under disturbed flow, hyperglycemia, and hyperlipidemia conditions. We also summarized the molecular mechanisms involved in vascular inflammation during atherogenesis based on platelet receptors and secretion of inflammatory factors. Finally, we highlighted the studies of platelet migration in atherogenesis. In general, we elaborated an atherogenic role of platelets and the aspects that should be further studied in the future.

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