"Affimer" synthetic protein scaffolds block oxidized LDL binding to the LOX-1 scavenger receptor and inhibit ERK1/2 activation.

In multicellular organisms, a variety of lipid-protein particles control the systemic flow of triacylglycerides, cholesterol, and fatty acids between cells in different tissues. The chemical modification by oxidation of these particles can trigger pathological responses, mediated by a group of membrane proteins termed scavenger receptors. The lectin-like oxidized low-density lipoprotein (LOX-1) scavenger receptor binds to oxidized low-density lipoprotein (oxLDL) and mediates both signaling and trafficking outcomes.

The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function.

Vascular endothelial growth factor receptor 2 (VEGFR2, encoded by KDR) regulates endothelial function and angiogenesis. VEGFR2 undergoes ubiquitination that programs this receptor for trafficking and proteolysis, but the ubiquitin-modifying enzymes involved are ill-defined. Herein, we used a reverse genetics screen for the human E2 family of ubiquitin-conjugating enzymes to identify gene products that regulate VEGFR2 ubiquitination and proteolysis.

VEGFR endocytosis: Implications for angiogenesis.

The binding of vascular endothelial growth factor (VEGF) superfamily to VEGF receptor tyrosine kinases (VEGFRs) and co-receptors regulates vasculogenesis, angiogenesis and lymphangiogenesis. A recurring theme is that dysfunction in VEGF signaling promotes pathological angiogenesis, an important feature of cancer and pro-inflammatory disease states. Endocytosis of basal (resting) or activated VEGFRs facilitates signal attenuation and endothelial quiescence.

Identification of FDA-approved drugs against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through computational virtual screening.

Unlabelled: The SARS-CoV-2 coronavirus is responsible for the COVID-19 outbreak, which overwhelmed millions of people worldwide; hence, there is an urgency to identify appropriate antiviral drugs. This study focuses on screening compounds that inhibit RNA-dependent RNA-polymerase (RdRp) essential for RNA synthesis required for replication of positive-strand RNA viruses. Computational screening against RdRp using Food and Drug Administration (FDA)-approved drugs identified ten prominent compounds with binding energies of more than - 10.

Monitoring VEGF-Stimulated Calcium Ion Flux in Endothelial Cells.

The endothelial response to vascular endothelial growth factor A (VEGF-A) regulates many aspects of animal physiology in health and disease. Such VEGF-A-regulated phenomena include vasculogenesis, angiogenesis, tumor growth and progression. VEGF-A binding to receptor tyrosine kinases such as vascular endothelial growth factor receptor 2 (VEGFR2 ) activates multiple signal transduction pathways and changes in homeostasis, metabolism, gene expression, cell proliferation, migration, and survival.

A multicentre review comparing long term outcomes of endoscopic vein harvesting versus open vein harvesting for coronary artery bypass surgery.

Background: Utilisation of the Endoscopic Vein Harvesting (EVH) technique has been increasing for coronary artery bypass grafting (CABG) for the last two decades. Some surgeons remain concerned about the long-term patency of the long saphenous vein harvested endoscopically compared to traditional Open Vein Harvesting (OVH). The aim of this study was to perform a retrospective analysis of the outcomes between EVH and OVH from three UK centres with 10 years follow-up.

Financial implications of using extracorporeal membrane oxygenation following heart transplantation.

Objectives: Primary graft dysfunction after heart transplant is associated with high morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) can be used to wean patients from cardiopulmonary bypass. This study retrospectively reviews a single-centre experience of post-transplant ECMO in regard to outcomes and associated costs.

A post-preservation vascular flush removes significant populations of donor leukocytes prior to lung transplantation.

Background: Donor leukocytes are intrinsically involved in acute lung allograft rejection, via self-presentation of donor antigens to recipient leukocytes. Therapeutic modalities to remove donor leukocytes are currently unavailable. We evaluated if a vascular flush immediately following preservation can be used for this purpose.

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation.

Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation. Isolated porcine hearts underwent hypothermic, cardioplegic perfusion for 8 h.

A Randomized Study Comparing the Incidence of Postoperative Pain After Phrenic Nerve Infiltration Vs Nonphrenic Nerve Infiltration During Thoracotomy.

Thoracotomy is a common surgical procedure performed worldwide for lung disease. Despite major advances in analgesia, patients still experience severe shoulder, central back and surgical incision site pain in the postoperative period. This study aimed to assess whether intraoperative phrenic nerve infiltration reduces the incidence of postoperative pain and improves peak flow volume measurements during incentive spirometry.

Receptor Tyrosine Kinase Ubiquitination and De-Ubiquitination in Signal Transduction and Receptor Trafficking.

Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes.

Ex-vivo flush of the limb allograft reduces inflammatory burden prior to transplantation.

Background: Passenger leucocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia.

Methods: Bilateral forelimbs from the same pig were procured and infused with preservation flush and stored on ice.

The effect of 1.5 T cardiac magnetic resonance on human circulating leucocytes.

Aims: Investigators have proposed that cardiovascular magnetic resonance (CMR) should have restrictions similar to those of ionizing imaging techniques. We aimed to investigate the acute effect of 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, and in a large cohort of patients in vivo.

Randomized Study Comparing the Effect of Carbon Dioxide Insufflation on Veins Using 2 Types of Endoscopic and Open Vein Harvesting.

Objective: The aim of the study was to assess whether the use of carbon dioxide insufflation has any impact on integrity of long saphenous vein comparing 2 types of endoscopic vein harvesting and traditional open vein harvesting.

Methods: A total of 301 patients were prospectively randomized into 3 groups. Group 1 control arm of open vein harvesting (n = 101), group 2 closed tunnel (carbon dioxide) endoscopic vein harvesting (n = 100) and Group 3 open tunnel (carbon dioxide) endoscopic vein harvesting (open tunnel endoscopic vein harvesting) (n = 100).

Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting: The VICO Randomized Clinical Trial (Vein Integrity and Clinical Outcomes).

Background: Current consensus statements maintain that endoscopic vein harvesting (EVH) should be standard care in coronary artery bypass graft surgery, but vein quality and clinical outcomes have been questioned. The VICO trial (Vein Integrity and Clinical Outcomes) was designed to assess the impact of different vein harvesting methods on vessel damage and whether this contributes to clinical outcomes after coronary artery bypass grafting.

Methods: In this single-center, randomized clinical trial, patients undergoing coronary artery bypass grafting with an internal mammary artery and with 1 to 4 vein grafts were recruited.

Characterizing the early inflammatory contribution of the donor kidney following reperfusion.

Background: Donor kidneys contain a large reservoir of passenger leucocytes that contribute to acute rejection via direct alloantigen presentation and pro-inflammatory cytokine secretion. However, the early contribution of these cells following revascularization has not previously been described. We performed a secondary, high-volume preservation flush following cold storage to characterize the inflammatory contribution of the donor kidney upon reperfusion.

Normothermic Perfusion Induces Donor-Derived Leukocyte Mobilization and Removal Prior to Renal Transplantation.

Introduction: normothermic perfusion offers an alternative method of organ preservation, allowing donor kidneys to be reanimated and evaluated prior to transplantation. Beyond preservation, it can be used to characterize the immunological contribution of the donor kidney in isolation. Furthermore, it has the potential to be used as an immunomodulatory strategy to manipulate donor kidneys prior to transplantation.

A comprehensive review on learning curve associated problems in endoscopic vein harvesting and the requirement for a standardised training programme.

Endoscopic vein harvesting is becoming one of the most favourable vein harvesting techniques in multiple bypass coronary surgery, due to its short term post-operative benefits with high patient satisfaction. However, long-term graft patency has been both supported and questioned in the literature. Graft failure can be affected by harvesting methods and operator's experience.

A randomized study comparing traditional monofilament knotted sutures with barbed knotless sutures for donor leg wound closure in coronary artery bypass surgery.

Objectives: Surgical knots on the suture line provide an anchoring function, but also represent a potential source of infection and irritation on the donor leg after coronary artery bypass surgery. Knotless barbed sutures were designed to prevent knot-related complications. This study compared knot-related wound complication rates between patients receiving traditional monofilament sutures and those receiving barbed knotless sutures for closure of the donor leg.

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion.

Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation.

Does the introduction of a comprehensive structured training programme for endoscopic vein harvesting improve conduit quality? A multicentre pilot study.

Objectives: Endoscopic vein harvesting is one of the most popular minimally invasive vein-harvesting techniques for coronary artery bypass graft surgery. It is associated with improved cosmetic outcome and fewer wound-related problems compared with the conventional open technique. However, its efficacy with regard to conduit damage and long-term patency has recently been questioned.

Histological and immunohistochemical evaluation of human saphenous vein harvested by endoscopic and open conventional methods.

Objectives: The introduction of endoscopic saphenous vein harvesting (ESVH) has been reported to decrease saphenectomy-associated wound pain and infection, compared with the traditional open conventional saphenous vein harvesting (OCSVH) technique. Despite all these benefits, the rate of adoption among surgeons has been variable. Criticism of this technique centres on the risk of injury at the time of vein harvest with its potential detrimental effect on structural viability and long-term patency.

Heart rate after cardiac transplantation-lessons from the tortoise and the shrew.

There is a striking consistency in the total number of heart beats accrued over a lifetime across a range of animal species despite vast differences in size. Moreover, an inverse relationship is observed between heart rate and lifespan, leading to speculation that elevated heart rate could significantly affect longevity. It is the aim of this review to analyze heart rate as a contributing factor in defining the functional lifespan of the transplanted human heart, which may unavoidably determine the longevity of the recipient.

Second line options for hyperlipidemia management after cardiac transplantation.

Despite widespread statin therapy, 91% of cardiac transplant patients have hyperlipidemia within 5 years from cardiac transplantation. The implications of this are profound, particularly given that coronary allograft vasculopathy is a leading cause of death. Unfortunately the solution is not easy, with problems of toleration at higher statin doses and a lack of good quality evidence for second line agents.