Publications by authors named "John Cooke"

Background: Dupuytren's contracture is caused by nodules and cords which pull the fingers towards the palm of the hand. Treatments include limited fasciectomy surgery, collagenase injection and needle fasciotomy. There is limited evidence comparing limited fasciectomy with collagenase injection.

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  • EphrinB2 is crucial for promoting the formation of blood and lymph vessels during embryo development and plays a significant role in cardiac lymphangiogenesis after a heart attack (myocardial infarction, MI).
  • The study found that EphrinB2 helps prevent heart remodeling and dysfunction post-MI by activating pathways involved in lymphangiogenesis, with its absence leading to worsening heart conditions.
  • Mechanistically, EphrinB2 enhances the proliferation and migration of lymphatic endothelial cells, boosts the activity of a specific transcription factor (ISL1), and its effects are diminished when the VEGFR3 pathway is inhibited, highlighting its importance in cardiac recovery after MI.
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The focus of current research work was to develop and validate size-exclusion chromatography method and develop and evaluate gel formulation of deferoxamine conjugated with PEGylated carbon nanoparticles (DEF-PEG-CNP) for topical delivery. Size-exclusion chromatography-based method was validated as per ICH guidelines. Effect of Carbopol® 974P and Transcutol® on the nanoparticles' permeation was studied by 3-level full factorial design of experiment.

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  • - The study compares the effectiveness of two treatments for Dupuytren's contracture: collagenase injection and limited fasciectomy, using a randomized controlled trial with 672 participants
  • - The main measurement tool used was the Patient Evaluation Measure-Hand Health Profile (PEM), where scores range from 0 to 100, with higher scores indicating worse hand health; results showed a mean score of 17.8 for the collagenase group and 11.9 for the limited-fasciectomy group at 1 year
  • - The findings concluded that collagenase injection was not as effective as limited fasciectomy after one year, with fewer complications reported in the collagenase group (1.8%) compared to the limited-fasc
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  • Familial hypercholesterolemia (FH) is a genetic condition that causes high levels of LDL cholesterol, increasing the risk of heart disease.
  • Current treatments for FH are limited and not very effective at reducing cholesterol or heart disease risk.
  • New nucleic acid therapies, like DNA and RNA-based treatments, show promise in directly addressing the causes of FH and have made progress in clinical applications, offering a potential alternative to traditional medications.
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Myocardial recovery is characterized by a return toward normal structure and function of the heart after an injury. Mechanisms of myocardial recovery include restoration and/or adaptation of myocyte structure and function, mitochondrial activity and number, metabolic homeostasis, electrophysiological stability, extracellular matrix remodeling, and myocardial perfusion. Myocardial regeneration is an element of myocardial recovery that involves the generation of new myocardial tissue, a process which is limited in adult humans but may be therapeutically augmented.

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Purpose Of Review: Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption.

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Background And Aims: In chronic ischaemic heart failure, revascularisation strategies control symptoms but are less effective in improving left ventricular ejection fraction (LVEF). The aim of this trial is to investigate the safety of cardiac shockwave therapy (SWT) as a novel treatment option and its efficacy in increasing cardiac function by inducing angiogenesis and regeneration in hibernating myocardium.

Methods: In this single-blind, parallel-group, sham-controlled trial (cardiac shockwave therapy for ischemic heart failure, CAST-HF; NCT03859466) patients with LVEF ≤40% requiring surgical revascularisation were enrolled.

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Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing. In this study, we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway, a molecular driver of endochondral ossification. We hypothesize that using an mRNA-based therapeutic encoding β-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes.

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Vasculopathies occur 15 years earlier in individuals with diabetes mellitus (DM) as compared to those without, but the underlying mechanisms driving diabetic vasculopathy remain incompletely understood. Endothelial cells (ECs) and macrophages (MΦ) are critical players in vascular wall and their crosstalk is crucial in diabetic vasculopathy. In diabetes, EC activation enables monocyte recruitment, which transmigrate into the intima and differentiate into macrophages (MΦ).

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Introduction: Faculty development (FD) is integral to the implementation of educational programmes. However, attracting new faculty is challenging. Competition is a motivator for learning at an undergraduate level; however, incorporating competition to engage faculty in continued FD has not been explored.

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Background: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored.

Methods: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs.

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The ability of endothelial cells to sense and respond to dynamic changes in blood flow is critical for vascular homeostasis and cardiovascular health. The mechanical and geometric properties of the nuclear and cytoplasmic compartments affect mechanotransduction. We hypothesized that alterations to these parameters have resulting mechanosensory consequences.

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  • Inflammation helps protect our bodies from injuries and infections, and is important for healing tissues after they get hurt.
  • Special immune cells are known for their role in cleaning up debris and helping repair blood vessels, but regular body cells can also help out.
  • This review talks about how these regular cells can change and adapt in response to inflammation, a process called transflammation, and how new technologies might help us use this for healing purposes.
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  • * CVD risk may increase for cancer survivors due to long-term complications from cancer and its treatments, with cellular senescence playing a significant role in this relationship.
  • * The article seeks to explore the mechanisms connecting premature cellular aging to CVD in cancer survivors and suggests future research directions for a deeper understanding of this complex issue.
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  • SENP2 is a crucial protein that helps protect against atherosclerosis; however, when phosphorylated at T368 under disturbed flow, it loses its function and leads to endothelial cell activation.
  • Researchers developed a specific antibody and used CRISPR/Cas9 to create mice with a mutation at the S344 phosphorylation site of SENP2 and studied its effects on endothelial cell behavior under different flow conditions.
  • The study found that normal flow (L-flow) causes phosphorylation of SENP2 at S344, which inhibits harmful endothelial cell activation, while mutations in this site lead to increased inflammation, migration, and cell proliferation, making atherosclerosis worse, especially in female mice.
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  • Deep skin wounds are serious and often need special skin grafts to heal properly.
  • A new method using human skin cells can take less skin from donors and still help healing, but old skin cells don’t work as well.
  • Researchers found that adding a special ingredient called hTERT to skin cells can help them grow better and heal faster in tests with mice.
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  • Excess sodium intake contributes to hypertension through lymphatic dysfunction, with a focus on the role of the adenosine A2A receptor (A2AR) in lymphatic endothelial cells (LECs) during salt-induced hypertension.* -
  • Mice with LEC-specific knockout of A2AR showed higher blood pressure and decreased lymphatic density, while A2AR activation using an agonist improved lymphatic density and lowered blood pressure, indicating its importance in regulating lymphatic function.* -
  • The findings suggest A2AR-mediated signaling promotes lymphangiogenesis and sodium balance independently of VEGF, pointing to its potential as a therapeutic target for managing salt-sensitive hypertension.*
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Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression.

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Background: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation.

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Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with endothelial dysfunction. We aimed to determine the effects of prior coronavirus disease 2019 (COVID-19) on the coronary microvasculature accounting for time from COVID-19, disease severity, SARS-CoV-2 variants, and in subgroups of patients with diabetes and those with no known coronary artery disease.

Methods And Results: Cases consisted of patients with previous COVID-19 who had clinically indicated positron emission tomography (PET) imaging and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior infection.

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Electrical stimulation, the application of an electric field to cells and tissues grown in culture to accelerate growth and tight junction formation among endothelial cells, could be impactful in cardiovascular tissue engineering, allotransplantation, and wound healing. Using Electrical Cell Stimulation And Recording Apparatus (ECSARA), the exploration of the stimulatory influences of electric fields of different magnitude and frequencies on growth and proliferation, trans endothelial electrical resistance (TEER) and gene expression of human endothelia cells (HUVECs) were explored. Within the range of endogenous electrical pulses studied, frequency was found to be more significant ( = 0.

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