Does plasmin have anticoagulant activity?

The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy

The Hussey Plow Co., North Berwick, Maine

An undated (but believed to be from 1895) catalog for the Hussey Plow Company of North Berwick, Maine.https://digicom.bpl.lib.me.us/books_pubs/1234/thumbnail.jp

Challenges for heart disease stem cell therapy

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress

Kindlin-2 (Mig-2): a co-activator of β3 integrins

Integrin activation is essential for dynamically linking the extracellular environment and cytoskeletal/signaling networks. Activation is controlled by integrins' short cytoplasmic tails (CTs). It is widely accepted that the head domain of talin (talin-H) can mediate integrin activation by binding to two sites in integrin β's CT; in integrin β3 this is an NPLY747 motif and the membrane-proximal region. Here, we show that the C-terminal region of integrin β3 CT, composed of a conserved TS752T region and NITY759 motif, supports integrin activation by binding to a cytosolic binding partner, kindlin-2, a widely distributed PTB domain protein. Co-transfection of kindlin-2 with talin-H results in a synergistic enhancement of integrin αIIbβ3 activation. Furthermore, siRNA knockdown of endogenous kindlin-2 impairs talin-induced αIIbβ3 activation in transfected CHO cells and blunts αvβ3-mediated adhesion and migration of endothelial cells. Our results thus identify kindlin-2 as a novel regulator of integrin activation; it functions as a coactivator

The Plasminogen System in Regulating Stem Cell Mobilization

The treatment of patients with hematopoietic progenitor and stem cells (HPSCs) to reconstitute hematopoiesis after myeloablative therapy or to repair ischemia after myocardial infarction has significantly improved clinical outcomes. Successful blood or bone marrow transplants require a sufficient number of HPSCs capable of homing to the injured site to regenerate tissue. Granulocyte-colony stimulating factor (G-CSF) is widely used clinically for stem cell mobilization. However, in some patients the response is poor, thus a better understanding of the mechanisms underlying G-CSF-regulated stem cell mobilization is needed. The pasminogen (Plg) system is the primary fibrinolytic pathway responsible for clot dissolution after thrombosis. Recent evidence suggests that Plg plays a pivotal role in stem cell mobilization from the bone marrow to the peripheral circulation, particularly in HPSC mobilization in response to G-CSF. This paper will discuss the potential mechanisms by which the Plg system regulates stem cell mobilization, focusing on stepwise proteolysis and signal transduction during HPSC egress from their bone marrow niche. Clear elucidation of the underlying mechanisms may lead to the development of new Plg-based therapeutic strategies to improve stem cell mobilization in treating hematological and cardiovascular diseases

Neuroplasticity Associated with Tactile Language Communication in a Deaf-Blind Subject

A long-standing debate in cognitive neuroscience pertains to the innate nature of language development and the underlying factors that determine this faculty. We explored the neural correlates associated with language processing in a unique individual who is early blind, congenitally deaf, and possesses a high level of language function. Using functional magnetic resonance imaging (fMRI), we compared the neural networks associated with the tactile reading of words presented in Braille, Print on Palm (POP), and a haptic form of American Sign Language (haptic ASL or hASL). With all three modes of tactile communication, indentifying words was associated with robust activation within occipital cortical regions as well as posterior superior temporal and inferior frontal language areas (lateralized within the left hemisphere). In a normally sighted and hearing interpreter, identifying words through hASL was associated with left-lateralized activation of inferior frontal language areas however robust occipital cortex activation was not observed. Diffusion tensor imaging -based tractography revealed differences consistent with enhanced occipital-temporal connectivity in the deaf-blind subject. Our results demonstrate that in the case of early onset of both visual and auditory deprivation, tactile-based communication is associated with an extensive cortical network implicating occipital as well as posterior superior temporal and frontal associated language areas. The cortical areas activated in this deaf-blind subject are consistent with characteristic cortical regions previously implicated with language. Finally, the resilience of language function within the context of early and combined visual and auditory deprivation may be related to enhanced connectivity between relevant cortical areas

Improving the affinity of fibroblasts for bacterial cellulose using carbohydrate-binding modules fused to RGD

The attachment of cells to biomedical materials can be improved by using adhesion sequences, such as Arg-Gly-Asp (RGD), found in several extracellular matrix proteins. In this work, bifunctional recombinant proteins, with a Cellulose-Binding Module (CBM), from the cellulosome of Clostridium thermocellum and cell binding sequences - RGD, GRGDY - were cloned and expressed in E.coli. These RGD-containing cellulose binding proteins were purified and used to coat bacterial cellulose fibres. Its effect on the cell adhesion/biocompatibility properties was tested using a mouse embryo fibroblasts culture. Bacterial cellulose (BC) secreted by Gluconacetobacter xylinus (=Acetobacter xylinum) is a material with unique properties and promising biomedical applications. CBMs adsorbs specifically and tightly on cellulose. Thus, they are a useful tool to address the fused RGD sequence (or other bioactive peptides) to the cellulose surface, in a specific and simple way. Indeed, fibroblasts exhibit improved ability to interact with bacterial cellulose sheets coated with RGD-CBM proteins, as compared with cellulose treated with the CBM, that is, without the adhesion peptide. The effect of the several fusion proteins produced was analyzed.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil)Fundação para a Ciência e a Tecnologia (FCT