Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs.

The central nervous system (CNS) influences the immune system generally by regulating the systemic concentration of humoral substances (e.g., cortisol and epinephrine), whereas the peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions/connections.

Optimized flow cytometric detection of transient receptor potential vanilloid-1 (TRPV1) in human hematological malignancies.

The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers, including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and presents an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient samples.

Estradiol-Responsive miR-365a-3p Interacts with Tissue Factor 3'UTR to Modulate Tissue Factor-Initiated Thrombin Generation.

Background: High estradiol (E) levels are linked to an increased risk of venous thromboembolism; however, the underlying molecular mechanism(s) remain poorly understood. We previously identified an E-responsive microRNA (miR), miR-494-3p, that downregulates protein S expression, and posited additional coagulation factors, such as tissue factor, may be regulated in a similar manner via miRs.

Objectives: To evaluate the coagulation capacity of cohorts with high physiological E, and to further characterize novel E-responsive miR and miR regulation on tissue factor in E-related hypercoagulability.

Compression Socks Reduce Running-Induced Intestinal Damage.

Zadow, EK, Edwards, KH, Kitic, CM, Fell, JW, Adams, MJ, Singh, I, Kundur, A, Johnstone, ANB, Crilly, J, Bulmer, AC, Halson, SL, and, and Wu, SSX. Compression socks reduce running-induced intestinal damage. J Strength Cond Res 36(9): 2461-2464, 2022-Exercise is associated with a reduction in splanchnic blood flow that leads to the disruption of intestinal epithelium integrity, contributing to exercise-induced gastrointestinal syndrome.

Coronavirus (COVID-19), Coagulation, and Exercise: Interactions That May Influence Health Outcomes.

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality.

Shedding of soluble glycoprotein VI is neither affected by animal-derived antibeta-2-glycoprotein 1 antibodies nor IgG fractions from patients with systemic lupus erythematosus.

: Antibeta-2-glycoprotein 1 (antiβ2GP1) antibodies are associated with increased risk of thrombosis in patients with systemic lupus erythematosus (SLE). The specific effect(s) of antiβ2GP1 antibodies on platelets are unclear. Platelet activation in response to antiplatelet antibodies has been shown to induce shedding of the ectodomain of the platelet collagen receptor, glycoprotein VI (GPVI), releasing soluble GPVI (sGPVI).

Deep vein thrombosis in a well-trained masters cyclist, is popliteal vein entrapment syndrome to blame?

Whilst athletes are the epitome of health, venous thromboembolisms (VTE) including deep vein thrombosis and pulmonary embolism have been demonstrated to occur in well-trained athletes. VTE is frequently misdiagnosed and poorly treated within this population, often resulting in career or life-threatening ramifications. Furthermore, VTE risk rises with increasing age (> 40 years), potentially affecting masters athletes.

Acquired and Genetic Thrombotic Risk Factors in the Athlete.

While athletes are often considered the epitome of health due to their physique and lowered potential for metabolic and cardiovascular diseases, they may also be at risk for the onset and development of venous thromboembolism (VTE). In an attempt to achieve and remain competitive, athletes are frequently exposed to numerous athlete-specific risk factors, which may predispose them to VTE through the disruption of factors associated with Virchow's triad (i.e.

Crossmatching Maternal and Fetal Blood in Sheep.

We investigated the incidence of ex vivo incompatibility between ovine maternal RBC and fetal plasma. Time-mated singleton pregnant ewes (n = 8) underwent cesarean delivery of the fetus; at the time of delivery, paired maternal and fetal blood samples were collected and subsequently separated for storage as packed RBC and fresh frozen plasma. Gel column crossmatching was performed 3 to 4 wk later.

Synergistic inhibitory effect of capsaicin and dihydrocapsaicin on in-vitro platelet aggregation and thromboxane formation.

: Capsaicinoids, including capsaicin (CAP) and dihydrocapsaicin (DHC), the pungent principles of pepper fruits, individually inhibit in-vitro platelet aggregation. However, their effects, when present together, are not known. The aims of this study were to compare the effects of CAP and DHC alone, and in combination in the ratio that they are found in chilies (∼60% CAP : 40% DHC), on in-vitro platelet aggregation, platelet count and thromboxane B2 (TXB2) formation.

Time of day and short-duration high-intensity exercise influences on coagulation and fibrinolysis.

Exercise has been demonstrated to have considerable effects upon haemostasis, with activation dependent upon the duration and intensity of the exercise bout. In addition, markers of coagulation and fibrinolysis have been shown to possess circadian rhythms, peaking within the morning (0600-1200 h). Therefore, the time of day in which exercise is performed may influence the activation of the coagulation and fibrinolytic systems.

Further Investigations of the Effects of Anti-βGP1 Antibodies on Collagen-Induced Platelet Aggregation.

Anti-beta-2-glycoprotein 1 (anti-βGP1) antibodies are associated with increased thrombotic risk in patients with autoimmune disease. There is conflicting evidence on the effects of anti-βGP1 antibodies on platelets, with both enhanced and inhibited aggregation previously reported. However, previous studies did not include isotype antibodies to ensure the observed effects were due to anti-βGP1 antibodies.

TRPV1 Channels in Immune Cells and Hematological Malignancies.

Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation.

Expression of CCR6 on B cells in systemic lupus erythematosus patients.

B cells are known to play a dominant pathogenic role in autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. In recent times, the chemokine receptor CCR6 and its cognate ligand CCL20 have been shown to play a role in the fundamental kinetics of germinal centres and B cell responses. As CCR6 is found on B cells and is upregulated after activation, we investigated the expression of CCR6 on naive, pre-germinal centre (GC), GC/plasma cell and memory B cells in peripheral B cells of SLE patients and healthy controls using flow cytometry.

Changes to fibrinolysis in patients with systemic lupus erythematosus are associated with endothelial cell damage and inflammation, but not antiphospholipid antibodies.

We investigated whether changes to fibrinolysis were associated with other manifestations of systemic lupus erythematosus (SLE), including antiphospholipid (APL) antibody status, endothelial damage, and inflammation. Ninety-four patients (36 SLE patients, 58 healthy controls) were recruited from Tasmania, Australia. Circulating levels of plasminogen, α2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured, as well as APL antibodies (including lupus anticoagulant, anticardiolipin, and antibeta-2 glycoprotein-1 antibodies), soluble E-selectin, and interleukin-6.

Capsaicin-Induced Death of Human Haematological Malignant Cell Lines Is Independent of TRPV1 Activation.

The effect of the plant-derived vanilloid, capsaicin (CAP), on the metabolic activity of THP-1, U266B1 and U937 hematological malignancy cells was determined. CAP reduced metabolic activity in a concentration-dependent manner in the three cell lines. A biphasic effect was observed on THP-1 cells (EC50: IC50 (95% CI) 32.

βGP1, Anti-βGP1 Antibodies and Platelets: Key Players in the Antiphospholipid Syndrome.

Anti-beta 2 glycoprotein 1 (anti-βGP1) antibodies are commonly found in patients with autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Their presence is highly associated with increased risk of vascular thrombosis and/or recurrent pregnancy-related complications. Although they are a subtype of anti-phospholipid (APL) antibody, anti-βGP1 antibodies form complexes with βGP1 before binding to different receptors associated with anionic phospholipids on structures such as platelets and endothelial cells.

Inhibition of platelet aggregation by vanilloid-like agents is not mediated by transient receptor potential vanilloid-1 channels or cannabinoid receptors.

Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N-oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid.

Serum metabolic profile predicts adverse central haemodynamics in patients with type 2 diabetes mellitus.

Aims: People with type 2 diabetes mellitus (T2DM) have abnormal peripheral and central haemodynamics at rest and during exercise, probably due to metabolic perturbations, but mechanisms are unknown. We used untargeted metabolomics to determine the relationships between metabolic perturbations and haemodynamics (peripheral and central) measured at rest and during exercise.

Methods: Serum samples from 39 participants with T2DM (62 ± 9 years; 46 % male) and 39 controls (52 ± 10 years; 51 % male) were analysed by liquid chromatography-mass spectrometry, nuclear magnetic resonance spectroscopy and principal component analysis.

Association of von Willebrand factor blood levels with exercise hypertension.

Purpose: A hypertensive response to moderate intensity exercise (HRE) is associated with increased cardiovascular risk. The mechanisms of an HRE are unclear, although previous studies suggest this may be due to haemostatic and/or haemodynamic factors. We investigated the relationships between an HRE with haemostatic and hemodynamic indices.

Tissue factor pathway inhibitor: then and now.

Tissue factor pathway inhibitor (TFPI) is the major physiological regulator of tissue factor (TF)-induced blood coagulation. TFPI inhibits the TF-activated factor VII (FVIIa) complex in an activated factor X (FXa)-dependent manner, helping to control thrombin generation and ultimately fibrin formation. The importance of TFPI is demonstrated in models of hemophilia where lower levels of FVIII or FIX are insufficient to overcome its inhibitory effect, resulting in a bleeding phenotype.

Vanilloid-like agents inhibit aggregation of human platelets.

Introduction: Plant-derived and endogenous vanilloid-like agents exert their effects on cells through transient receptor potential vanilloid-1 (TRPV1). Little is known about the effects of these agents on platelet aggregation. We investigated the effect of various vanilloid-like agents on in-vitro platelet aggregation and tested whether this action is mediated through TRPV1.