Identification and functional characterization of multiple haemadins and an oligomeric decorsin in the Asian land leech Haemadipsa interrupta.

Haematophagous leeches rely on a broad variety of bioactive compounds to secure a sufficient blood meal from their vertebrate prey. Both the primary (platelet aggregation) and secondary (blood coagulation) haemostasis are the main targets of action. The platelet aggregation inhibitor decorsin was first described in the North American leech, Macrobdella decora Say, 1824, whereas the bivalent thrombin inhibitor hirudin was originally identified in the European medicinal leech, Hirudo medicinalis Linnaeus, 1758.

Enhanced platelet sensitization is accompanied by increased expression of the transporter MRP4 and elevated plasma S1P levels in mild COVID-19 convalescents.

Viral infections can lead to platelet activation and hemostatic complications. However, the extent to which platelet reactivity remains altered after convalescence, contributing to long-term health impairments as observed after COVID-19 is not yet fully understood. Therefore, we conducted a cohort study (DRKS00025217) to determine platelet function in individuals convalesced from mild COVID-19.

Adherence to drug therapy in patients with heart failure associated with reduced ejection fractions (HFrEF) during cardiac rehabilitation and after 3 and 6 months.

Introduction: Heart failure represents a major challenge for healthcare systems worldwide. Rehabilitation is recommended as an important pillar of therapy for these patients, especially for those with reduced left ventricular ejection fraction (HFrEF: heart failure with reduced ejection fraction).

Methods: The data collected in this multi-center project provide information on the rates of patients with HFrEF who were treated in five German rehabilitation facilities and whether the patients adhered to drug therapy at 3-/6-month follow-up.

The Putative S1PR1 Modulator ACT-209905 Impairs Growth and Migration of Glioblastoma Cells In Vitro.

Glioblastoma (GBM) is still a deadly tumor due to its highly infiltrative growth behavior and its resistance to therapy. Evidence is accumulating that sphingosine-1-phosphate (S1P) acts as an important tumor-promoting molecule that is involved in the activation of the S1P receptor subtype 1 (S1PR1). Therefore, we investigated the effect of ACT-209905 (a putative S1PR1 modulator) on the growth of human (primary cells, LN-18) and murine (GL261) GBM cells.

Standardised Exercise Prescription for Patients with Chronic Coronary Syndrome and/or Heart Failure: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training, as part of multidisciplinary rehabilitation, is a key component in the management of patients with chronic coronary syndrome (CCS) and/or congestive heart failure (CHF), physicians and exercise professionals disagree among themselves on the type and characteristics of the exercise to be prescribed to these patients, and the exercise prescriptions are not consistent with the international guidelines. This impacts the efficacy and quality of the intervention of rehabilitation. To overcome these barriers, a digital training and decision support system [i.

Sphingosine-1-phosphate levels are inversely associated with left ventricular and atrial chamber volume and cardiac mass in men : The Study of Health in Pomerania (SHIP).

Aims: Sphingosine-1-phosphate (S1P) is a signaling lipid, which is involved in several cellular processes including cell growth, proliferation, migration and apoptosis. The associations of serum S1P levels with cardiac geometry and function are still not clear. We investigated the associations of S1P with cardiac structure and systolic function in a population-based sample.

[Systematic Reviews on the Effectiveness of Multidisciplinary Rehabilitation].

Systematic reviews and meta-analyses of clinical trials are considered to represent the highest level of scientific evidence in clinical medicine provided internationally accepted guidelines and checklists are followed.In systematic reviews and meta-analyses all clinical studies focussing a specific predefined clinical question are collected and evaluated. The results of systematic reviews strongly depend on the study protocol, including the exact definition of the population of interest, the therapeutic intervention under consideration and, last not least, the time period of observation.

tRNA-like Transcripts from the Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions.

The evolutionary conserved gene cluster generates large noncoding transcripts remaining nuclear, while tRNA-like transcripts (mascRNA, menRNA) enzymatically generated from these precursors translocate to the cytosol. Whereas functions have been assigned to the nuclear transcripts, data on biological functions of the small cytosolic transcripts are sparse. We previously found and mice to display massive atherosclerosis and vascular inflammation.

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients.

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB.

Platelet-Derived S1P and Its Relevance for the Communication with Immune Cells in Multiple Human Diseases.

Sphingosine-1-phosphate (S1P) is a versatile signaling lipid involved in the regulation of numerous cellular processes. S1P regulates cellular proliferation, migration, and apoptosis as well as the function of immune cells. S1P is generated from sphingosine (Sph), which derives from the ceramide metabolism.

Sphingosine-1-phosphate and vascular disease in the general population.

Background And Aims: Sphingosine-1-phosphate (S1P) is a sphingolipid which influences the immune and vascular system. The relationship between S1P and vascular disease in the general population is currently unclear. We explored the relation between S1P and vascular markers, (i.

Course of disease and risk factors for hospitalization in outpatients with a SARS-CoV-2 infection.

We analyzed symptoms and comorbidities as predictors of hospitalization in 710 outpatients in North-East Germany with PCR-confirmed SARS-CoV-2 infection. During the first 3 days of infection, commonly reported symptoms were fatigue (71.8%), arthralgia/myalgia (56.

Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.

The multidrug resistance protein 4 (MRP4) is highly expressed in platelets and several lines of evidence point to an impact on platelet function. MRP4 represents a transporter for cyclic nucleotides as well as for certain lipid mediators. The aim of the present study was to comprehensively characterize the effect of a short-time specific pharmacological inhibition of MRP4 on signaling pathways in platelets.

Coagulation-independent effects of thrombin and Factor Xa: role of protease-activated receptors in pulmonary hypertension.

Aims: Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Vascular remodelling of pulmonary arteries, characterized by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a hallmark of PAH. Here, we aimed to systematically characterize coagulation-independent effects of key coagulation proteases thrombin and Factor Xa (FXa) and their designated receptors, protease-activated receptor (PAR)-1 and -2, on PASMCs in vitro and experimental PAH in vivo.

Pleiotropic Effects of the Protease-Activated Receptor 1 (PAR1) Inhibitor, Vorapaxar, on Atherosclerosis and Vascular Inflammation.

Background: Protease-activated receptor 1 (PAR1) and toll-like receptors (TLRs) are inflammatory mediators contributing to atherogenesis and atherothrombosis. Vorapaxar, which selectively antagonizes PAR1-signaling, is an approved, add-on antiplatelet therapy for secondary prevention. The non-hemostatic, platelet-independent, pleiotropic effects of vorapaxar have not yet been studied.

Preoperative Thrombocytosis is Not Associated with Overall Survival in 309 Glioblastoma Patients.

Background:  In recent years, a correlation of thrombocytosis and a worse prognosis was shown for many solid cancers, including glioblastoma multiforme (GBM).

Methods:  A retrospective review was performed for all patients with a histologically proven and first-diagnosed GBM between 2005 and 2015 in our department. Clinical and paraclinical parameters were acquired from patient documentation and structured for subsequent data analysis.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 2.

Background: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE).

Increased Sphingosine-1-Phosphate Serum Concentrations in Subjects with Periodontitis: A Matter of Inflammation.

Purpose: Periodontitis is an inflammatory disease of the oral cavity with an alarmingly high prevalence within the adult population. The signaling lipid sphingosine-1-phosphate (S1P) plays a crucial role in inflammatory and immunomodulatory responses. In addition to cardiovascular disease, sepsis and tumor entities, S1P has been recently identified as both mediator and biomarker in osteoporosis.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 1.

Background: Although cardiovascular rehabilitation (CR) is well accepted in general, CR-attendance and delivery still considerably vary between the European countries. Moreover, clinical and prognostic effects of CR are not well established for a variety of cardiovascular diseases.

Methods: The guidelines address all aspects of CR including indications, contents and delivery.

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice.

Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova.