scholarly journals Platelet functional activity: physiology and laboratory diagnostic methods

2019 ◽  
Vol 18 (3) ◽  
pp. 112-119
Author(s):  
E. A. Ponomarenko ◽  
A. A. Ignatova ◽  
D. V. Fedorova ◽  
P. A. Zharkov ◽  
M. A. Panteleev
Keyword(s):  
Wound Healing ◽  
Functional Activity ◽  
Vessel Wall ◽  
Inflammatory Diseases ◽  
Diagnostic Methods ◽  
Assessment Tools ◽  
Normal Functioning ◽  
Physiological Processes ◽  
Hemostatic System ◽  
Platelets Function

Platelets perform numerous important functions not only in the process of normal functioning of hemostatic system, but also in other physiological processes, such as: vessel wall integrity regulation, wound healing, inflammatory response. Its malfunction can be found in various diseases and conditions (including oncohematological disorders, solid tumors, inflammatory diseases, sepsis, autoimmune disorders), is triggered by injury or medications and can lead to dangerous consequences, such as bleeding and thrombosis. However, platelets functional activity quantity assessment tools are extremely limited, the perception what platelet functional activity is about is also quite unclear. This review considers platelets function, its' abnormalities, possibilities for its' assessment by existing methods as well as promising directions for their development.

Inflammation-Mediating Proteases: Structure, Function in (Patho) Physiology and Inhibition

2014 ◽  
Vol 21 (12) ◽  
pp. 1209-1229
Author(s):  
Mateja Mancek-Keber
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Structure Function ◽  
Allograft Rejection ◽  
Inflammatory Arthritis ◽  
Inflammatory Diseases ◽  
Vascular Diseases ◽  
Degrading Enzymes ◽  
Physiological Processes ◽  
Matrix Degrading Enzymes

Proteases regulating inflammation are versatile enzymes, usually extracellular matrix degrading enzymes that are involved in wound healing, angiogenesis, coagulation, development, apoptosis and other physiological processes. Their dysregulation and increased expression during inflammation can have devastating consequences, promoting etiology of vascular diseases, inflammatory arthritis, cancer, and allograft rejection. In this review several proteases (ADAMTS, granzymes, plasmin, and kallikreins) with different mechanisms and substrates are described in addition to their physiological roles and contribution to inflammation and inflammatory diseases. Inhibition of proteases may therefore represent an attractive strategy for treatment and herein we describe physiological and engineered inhibitors.

scholarly journals Factor XIII-A: An Indispensable “Factor” in Haemostasis and Wound Healing

2021 ◽  
Vol 22 (6) ◽  
pp. 3055
Author(s):  
Fahad S. M. Alshehri ◽  
Claire S. Whyte ◽  
Nicola J. Mutch
Keyword(s):  
Bone Marrow ◽  
Wound Healing ◽  
Crucial Role ◽  
Factor Xiii ◽  
Severe Bleeding ◽  
Bleeding Diathesis ◽  
Unknown Mechanism ◽  
Protein Substrates ◽  
Physiological Processes ◽  
Isopeptide Bonds

Factor XIII (FXIII) is a transglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA2B2, has an established function in haemostasis, with fibrin being its principal substrate. A deficiency in FXIII manifests as a severe bleeding diathesis emphasising its crucial role in this pathway. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage. The cellular form, a homodimer of the A subunits denoted FXIII-A, was perceived to remain intracellular, due to the lack of a classical signal peptide for its release. It is now apparent that FXIII-A can be externalised from cells, by an as yet unknown mechanism. Thus, three pools of FXIII-A exist within the circulation: plasma where it circulates in complex with the inhibitory FXIII-B subunits, and the cellular form encased within platelets and monocytes/macrophages. The abundance of this transglutaminase in different forms and locations in the vasculature reflect the complex and crucial roles of this enzyme in physiological processes. Herein, we examine the significance of these pools of FXIII-A in different settings and the evidence to date to support their function in haemostasis and wound healing.

scholarly journals The Function of the Histamine H4 Receptor in Inflammatory and Inflammation-Associated Diseases of the Gut

2021 ◽  
Vol 22 (11) ◽  
pp. 6116
Author(s):  
Bastian Schirmer ◽  
Detlef Neumann
Keyword(s):  
Inflammatory Diseases ◽  
Allergic Inflammation ◽  
Histamine H4 Receptor ◽  
Ongoing Research ◽  
Inflammatory Reactions ◽  
Beneficial Effects ◽  
Associated Diseases ◽  
Physiological Processes ◽  
H4 Receptor ◽  
Deficient Mice

Histamine is a pleiotropic mediator involved in a broad spectrum of (patho)-physiological processes, one of which is the regulation of inflammation. Compounds acting on three out of the four known histamine receptors are approved for clinical use. These approved compounds comprise histamine H1-receptor (H1R) antagonists, which are used to control allergic inflammation, antagonists at H2R, which therapeutically decrease gastric acid release, and an antagonist at H3R, which is indicated to treat narcolepsy. Ligands at H4R are still being tested pre-clinically and in clinical trials of inflammatory diseases, including rheumatoid arthritis, asthma, dermatitis, and psoriasis. These trials, however, documented only moderate beneficial effects of H4R ligands so far. Nevertheless, pre-clinically, H4R still is subject of ongoing research, analyzing various inflammatory, allergic, and autoimmune diseases. During inflammatory reactions in gut tissues, histamine concentrations rise in affected areas, indicating its possible biological effect. Indeed, in histamine-deficient mice experimentally induced inflammation of the gut is reduced in comparison to that in histamine-competent mice. However, antagonists at H1R, H2R, and H3R do not provide an effect on inflammation, supporting the idea that H4R is responsible for the histamine effects. In the present review, we discuss the involvement of histamine and H4R in inflammatory and inflammation-associated diseases of the gut.

scholarly journals Adenosine diphosphate contributes to wound healing in diabetic mice through P2Y1 and P2Y12 receptors activation

2020 ◽  
Author(s):  
Paula A. Borges ◽  
Ingrid Waclawiak ◽  
Janaína L. Georgii ◽  
Janaína F. Barros ◽  
Vanderlei S. Fraga-Junior ◽  
...  
Keyword(s):  
Wound Healing ◽  
Inflammatory Diseases ◽  
Purinergic Signaling ◽  
Adenosine Diphosphate ◽  
Treg Cells ◽  
Skin Wound ◽  
Diabetic Patients ◽  
Dependent Manner ◽  
Keratinocyte Proliferation ◽  
Wound Model

AbstractSeveral studies have shown the importance of purinergic signaling in various inflammatory diseases. In diabetes mellitus, there is an increase in the activity of some nucleotidases suggesting that this signaling may be affected in the diabetic skin. Thus, the aim of our study was to investigate the effect of ADP on wound healing in diabetic skin. Swis and C57BL/6 mice were pharmacologic induced to type 1 diabetes and submitted to a full-thickness excisional wound model to evaluate the effect of ADP as a topic treatment. Adenosine diphosphate accelerated cutaneous wound healing, improved the new tissue formation, and increased collagen deposit by positively modulating P2Y1 and P2Y12 and TGF-β production. In parallel, ADP reduced reactive oxygen species production and TNF-α levels, while increased IFNγ, IL-10 and IL-13 levels in the skin. Also, ADP induced the migration of neutrophils, eosinophils, mast cells, TCRγ4+, and TCRγ5+ cells while reduced Treg cells towards the lesion at day 7. In accordance, ADP increased the proliferation and migration of fibroblast, induced myofibroblast differentiation and keratinocyte proliferation in a P2Y12-dependent manner. We provide the first evidence of ADP acting as a potent mediator on skin wound resolution and a possible therapeutic approach for diabetic patients worldwide.

Study of melanin localization in the mature maleCalopteryx haemorrhoidalisdamselfly wings

2018 ◽  
Vol 25 (3) ◽  
pp. 874-877 ◽  
Author(s):  
Vi Khanh Truong ◽  
Jitraporn Vongsvivut ◽  
Nipuni Mahanamanam Geeganagamage ◽  
Mark J. Tobin ◽  
Pere Luque ◽  
...  
Keyword(s):  
Wound Healing ◽  
High Spatial Resolution ◽  
Western Mediterranean ◽  
Wing Membrane ◽  
Colour Variation ◽  
Physiological Processes ◽  
Wing Pigmentation ◽  
Males And Females ◽  
Ir Microspectroscopy ◽  
Defence Reactions

DamselfliesCalopteryx haemorrhoidalisexhibiting black wings are found in the western Mediterranean, Algeria, France, Italy, Spain and Monaco. Wing pigmentation is caused by the presence of melanin, which is involved in physiological processes including defence reactions, wound healing and sclerotization of the insect. Despite the important physiological roles of melanin, the presence and colour variation among males and females of theC. haemorrhoidalisspecies and the localization of the pigment within the wing membrane remain poorly understood. In this study, infrared (IR) microspectroscopy, coupled with the highly collimated synchrotron IR beam, was employed in order to identify the distribution of the pigments in the wings at a high spatial resolution. It was found that the melanin is localized in the procuticle of theC. haemorrhoidalisdamselfly wings, distributed homogeneously within this layer, and not associated with the lipids of the epicuticle.

scholarly journals Antiadhesive effect of fibrinogen: a safeguard for thrombus stability

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1541-1549 ◽  
Author(s):  
Valeryi K. Lishko ◽  
Timothy Burke ◽  
Tatiana Ugarova
Keyword(s):  
Wound Healing ◽  
Vessel Wall ◽  
Potent Inhibitor ◽  
Leukocyte Adhesion ◽  
Fibrin Clot ◽  
Flow Conditions ◽  
High Concentration ◽  
Fibrin Gel ◽  
Wall Injury

Abstract The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution.

Metalloproteinases and their inhibitors in angiogenesis

2003 ◽  
Vol 5 (23) ◽  
pp. 1-39 ◽  
Author(s):  
Marc A. Lafleur ◽  
Madeleine M. Handsley ◽  
Dylan R. Edwards
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Function ◽  
Proteolytic Enzymes ◽  
Biologically Relevant ◽  
Physiological Processes ◽  
Adam Family ◽  
Angiogenic Inhibitors ◽  
Membrane Type

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is an integral part of physiological processes such as embryonic development, the female reproductive cycle and wound healing. Angiogenesis is also central to a variety of pathologies including cancer, where it is recognised as being crucial for the growth of solid tumours. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, most notably MMP-2 and -9 and membrane-type-1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, liberation of angiogenic factors, production of endogenous angiogenic inhibitors, and the unmasking of cryptic biologically relevant sites in ECM components. This review brings together what is currently known about the functions of the MMPs and the closely related adamalysin metalloproteinase (ADAM) family in angiogenesis, and discusses how this information might be useful in manipulation of the angiogenic process, with a view to controlling aberrant neovascularisation.

scholarly journals NF-kappa B-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts.

1992 ◽  
Vol 176 (3) ◽  
pp. 787-792 ◽  
Author(s):  
D J Kessler ◽  
M P Duyao ◽  
D B Spicer ◽  
G E Sonenshein
Keyword(s):  
Wound Healing ◽  
Gene Transcription ◽  
Dermal Fibroblast ◽  
Regulatory Element ◽  
Interleukin 1 ◽  
Human Dermal Fibroblast ◽  
Nf Kappa B ◽  
Physiological Processes ◽  
Multiple Copies ◽  
Myc Gene

Interleukin 1 (IL-1) is a pluripotent cytokine involved in mediating a variety of physiological processes, including induction of cell proliferation upon wound healing. Treatment of quiescent FS-4 human dermal fibroblast cells with IL-1 activates c-myc gene transcription, and nuclear localization of NF-kappa B. Previously, we have noted that the murine c-myc gene contains two functional NF-kappa B sites located at -1101 to -1081 bp (upstream regulatory element [URE]) and +440 to +459 bp (internal regulatory element [IRE]) relative to the P1 promoter. Here we have demonstrated that IL-1 treatment induced binding of NF-kappa B-like proteins (p50/p65) to these c-myc elements. Heterologous promoter-CAT constructs driven by multiple copies of either the URE or IRE were IL-1 inducible when transfected into FS-4 cells. In contrast, constructs harboring elements with two G to C residue conversions, such that they were no longer able to bind NF-kappa B, were not responsive to IL-1. Mutation of these two base pairs at both NF-kappa B sites within a c-myc promoter/exon I-CAT construct, resulted in loss of inducibility with IL-1 upon transfection into quiescent FS-4 cells. Thus, IL-1 significantly induces c-myc expression through positive regulation by NF-kappa B, suggesting a role for this family of factors in activation of proliferation associated with wound healing.

Heme oxygenase-1 in neovascularisation: A diabetic perspective

2010 ◽  
Vol 104 (09) ◽  
pp. 424-431 ◽  
Author(s):  
Anna Grochot-Przeczek ◽  
Jozef Dulak ◽  
Alicja Jozkowicz
Keyword(s):  
Wound Healing ◽  
Heme Oxygenase ◽  
Tissue Regeneration ◽  
Hair Growth ◽  
Tumour Progression ◽  
Heme Oxygenase 1 ◽  
Blood Vessel Formation ◽  
Physiological Processes ◽  
Healing Tissue

SummaryNeovascularisation is crucial both for physiological processes, like development, wound healing, tissue regeneration, hair growth or menstrual cycle, and for pathological states, such as tumour progression, retinopathy and psoriasis. Blood vessel formation is orchestrated by numerous pro-angiogenic and anti-angiogenic factors, acting together to keep tight rein on this complicated, desirable but also dangerous process. One of the proteins important for neovascularisation is heme oxygenase-1 (HO-1), an enzyme degrading heme. This review focuses on the role of HO-1 in angiogenesis and vasculogenesis, having a closer look at the significance of this system in diabetes.

scholarly journals The Role of HDAC6 in Autophagy and NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Chang ◽  
Hao Li ◽  
Hui Hu ◽  
Yongqing Li ◽  
Tianbing Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Histone Deacetylase 6 ◽  
Physiological Processes ◽  
Class Iib ◽  
Underlying Mechanisms ◽  
Nlrp3 Inflammasomes ◽  
Insight Into

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.

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