Metabolites and Metabolic Functional Changes-Potential Markers for Endothelial Cell Senescence.

Accumulation of senescent endothelial cells (ECs) in vasculature represents a key step in the development of vascular aging and ensuing age-related diseases. Given that removal of senescent ECs may prevent disease and improve health and wellbeing, the discovery of novel biomarkers that effectively identify senescent cells is of particular importance. As crucial elements for biological pathways and reliable bioindicators of cellular processes, metabolites demand attention in this context.

Comorbidities and Angiogenic Regulators Affect Endothelial Progenitor Cell Subtype Numbers in a Healthy Volunteer Control Group.

Endothelial progenitor cells (EPCs) are stem cells that can repair injured blood vessels through neovascularisation. This is achieved through secretion of growth factors and endothelial maturation. EPC numbers and function have been studied to determine their diagnostic, prognostic and therapeutic potential in many ischaemic diseases such as stroke.

Senolytics and Senomorphics Targeting p38MAPK/NF-κB Pathway Protect Endothelial Cells from Oxidative Stress-Mediated Premature Senescence.

Oxidative stress is a prominent causal factor in the premature senescence of microvascular endothelial cells and the ensuing blood-brain barrier (BBB) dysfunction. Through the exposure of an in vitro model of human BBB, composed of brain microvascular endothelial cells (BMECs), astrocytes, and pericytes to HO, this study examined whether a specific targeting of the p38MAPK/NF-κB pathway and/or senescent cells could delay oxidative stress-mediated EC senescence and protect the BBB. Enlarged BMECs, displaying higher β-galactosidase activity, γH2AX staining, p16 expression, and impaired tubulogenic capacity, were regarded as senescent.

Hyperglycaemia perturbs blood-brain barrier integrity through its effects on endothelial cell characteristics and function.

Breakdown of blood-brain barrier (BBB) represents a key pathology in hyperglycemia-mediated cerebrovascular damage after an ischemic stroke. As changes in the level and nature of vasoactive agents released by endothelial cells (ECs) may contribute to BBB dysfunction, this study first explored the specific impact of hyperglycemia on EC characteristics and secretome. It then assessed whether secretome obtained from ECs subjected to normoglycaemia or hyperglycemia might regulate pericytic cytokine profile differently.

The Role of Stem Cells as Therapeutics for Ischaemic Stroke.

Stroke remains one of the leading causes of death and disability worldwide. Current reperfusion treatments for ischaemic stroke are limited due to their narrow therapeutic window in rescuing ischaemic penumbra. Stem cell therapy offers a promising alternative.

Analysis of endothelial progenitor cell subtypes as clinical biomarkers for elderly patients with ischaemic stroke.

Endothelial progenitor cells (EPCs), expressing markers for stemness (CD34), immaturity (CD133) and endothelial maturity (KDR), may determine the extent of post-stroke vascular repair. Given the prevalence of stroke in elderly, this study explored whether variations in plasmatic availability of certain EPC subtypes could predict the severity and outcome of disease in older patients. Blood samples were collected from eighty-one consented patients (≥ 65 years) at admission and days 7, 30 and 90 post-stroke.

Unusual inguinal mass: Ectopic seminal vesicle.

A 28-year-old male was referred to our radiology department with the complaint of inguinal mass. He had this mass since its childhood but has recent discomfort. First of all ultrasound was performed and it showed tubular structures connecting with each other.

TNF-α evokes blood-brain barrier dysfunction through activation of Rho-kinase and neurokinin 1 receptor.

Ischaemic stroke, accompanied by neuroinflammation, impairs blood-brain barrier (BBB) integrity through a complex mechanism involving activation of both RhoA/Rho kinase/myosin light chain-2 and neurokinin 1 receptor (NK1R). Using an in vitro model of human BBB composed of brain microvascular endothelial cells (BMEC), astrocytes and pericytes, this study examined the potential contributions of these elements to BBB damage induced by elevated availability of pro-inflammatory cytokine, TNF-α. Treatment of human BMECs with TNF-α significantly enhanced RhoA activity and the protein expressions of Rho kinase and phosphorylated Ser19MLC-2 while decreasing that of NK1R.

Substance P reversibly compromises the integrity and function of blood-brain barrier.

Background: Substance P (SP) plays a role in vasodilatation and tissue integrity through its receptor, neurokinin 1 (NK1R). However, its specific effect on blood-brain barrier (BBB) remains unknown.

Methods: The impact of SP on the integrity/function of human BBB model in vitro, composed of brain microvascular endothelial cells (BMECs), astrocytes and pericytes, was assessed by measurements of transendothelial electrical resistance and paracellular flux of sodium fluorescein (NaF), respectively in the absence/presence of specific inhibitors targeting NK1R (CP96345), Rho-associated protein kinase (ROCK; Y27632) and nitric oxide synthase (NOS; N(G)-nitro-L-arginine methyl ester).

Evaluation of Endothelial Progenitor Cell Characteristics as Clinical Biomarkers for Elderly Patients with Ischaemic Stroke.

Ageing impairs endothelial function and predisposes the person to ischaemic stroke (IS). Endothelial progenitor cells (EPCs) repair endothelial damage and induce post-ischaemic neovascularisation. Given the prevalence of IS in older population, this study explored whether changes in EPC number and function may reliably predict the type or outcome of stroke in patients ≥ 65 years of age.

The value of dual-energy computed tomography in the evaluation of myocarditis.

Purpose: The inflammation of the heart muscle is referred to as acute myocarditis. Cardiac magnetic resonance imaging (CMR) has become the primary method for a non-invasive assessment of myocardial inflammation. However, there are several drawbacks of CMR.

Outgrowth Endothelial Cell Conditioned Medium Negates TNF-α-Evoked Cerebral Barrier Damage: A Reverse Translational Research to Explore Mechanisms.

Improved understanding of the key mechanisms underlying cerebral ischemic injury is essential for the discovery of efficacious novel therapeutics for stroke. Through detailed analysis of plasma samples obtained from a large number of healthy volunteers (n = 90) and ischemic stroke patients (n = 81), the current study found significant elevations in the levels of TNF-α at baseline (within the first 48 h of stroke) and on days 7, 30, 90 after ischaemic stroke. It then assessed the impact of this inflammatory cytokine on an in vitro model of human blood-brain barrier (BBB) and revealed dramatic impairments in both barrier integrity and function, the main cause of early death after an ischemic stroke.

Delay of endothelial cell senescence protects cerebral barrier against age-related dysfunction: role of senolytics and senomorphics.

Accumulation of senescent cells in cerebrovasculature is thought to play an important role in age-related disruption of blood-brain barrier (BBB). Using an model of human BBB, composed of brain microvascular endothelial cells (BMECs), astrocytes and pericytes, this study explored the so-called correlative link between BMEC senescence and the BBB dysfunction in the absence or presence of functionally distinct senotherapeutics. Replicative senescence was deemed present at passage ≥19 where BMECs displayed shortened telomere length, reduced proliferative and tubulogenic potentials and increased NADPH oxidase activity, superoxide anion production (markers of oxidative stress), S-β-galactosidase activity and γ-H2AX staining.

Protein kinase C-β distinctly regulates blood-brain barrier-forming capacity of Brain Microvascular endothelial cells and outgrowth endothelial cells.

Outgrowth endothelial cells (OECs) provide an endogenous repair mechanism and thus maintain endothelial barrier integrity. As inhibition of protein kinase C-β (PKC-β) activity has been shown to attenuate endothelial damage in various pathological conditions including hyperglycaemia and ischaemic injury, the present study comparatively assessed the effect of LY333531, a PKC-β inhibitor, on the cerebral barrier integrity formed by OECs or human brain microvascular endothelial cells (HBMECs). To this end, an in vitro model of human BBB established by co-culture of astrocytes and pericytes with either OECs or HBMECs was exposed to 4 h of oxygen-glucose deprivation with/out LY333531 (0.

Establishment of an In Vitro Model of Human Blood-Brain Barrier to Study the Impact of Ischemic Injury.

The blood-brain barrier (BBB), mainly composed of brain microvascular endothelial cells, astrocyte end-feet, and pericytes, serves as a physical and biochemical barrier that selectively limits the passage of circulating molecules into the brain parenchyma. The disruption of its integrity and function is a major cause of increased mortality and disability among ischemic stroke patients. Hence, scrutiny of the cellular and molecular mechanisms that alter BBB permeability following an ischemic injury remains of paramount importance.

Effects of substance P on human cerebral microvascular endothelial cell line hCMEC/D3 are mediated exclusively through a truncated NK-1 receptor and depend on cell confluence.

The neuropeptide substance P (SP) mediates pain transmission, immune modulation, vasodilation and neurogenic inflammation. Its role in the peripheral nervous system has been well characterised. However, its actions on the blood-brain barrier (BBB) are less clear and warrant further study.

Inhibition of oxidative stress delays senescence and augments functional capacity of endothelial progenitor cells.

Ageing is characterised by a progressive loss of vascular endothelial function and integrity. Endothelial progenitor cells (EPCs) play an integral role in endothelial regeneration but are prone to age-dependent changes which may accelerate their senescence and diminish their availability and functionality. Considering these, we firstly investigated the quantity of circulating EPCs in older (73.

Treatment with outgrowth endothelial cells protects cerebral barrier against ischemic injury.

Background And Aims: We have previously reported that outgrowth endothelial cells (OECs) restore cerebral endothelial cell integrity through effective homing to the injury site. This study further investigates whether treatment with OECs can restore blood-brain barrier (BBB) function in settings of ischemia-reperfusion injury both in vitro and in vivo.

Methods: An in vitro model of human BBB was established by co-culture of astrocytes, pericytes, and human brain microvascular endothelial cells (HBMECs) before exposure to oxygen-glucose deprivation alone or followed by reperfusion (OGD±R) in the absence or presence of exogenous OECs.

Outgrowth endothelial progenitor cells restore cerebral barrier function following ischaemic damage: The impact of NOX2 inhibition.

Disruption of blood-brain barrier (BBB), formed mainly by human brain microvascular endothelial cells (HBMECs), constitutes the major cause of mortality following ischaemic stroke. This study investigates whether OECs (outgrowth endothelial cells) can restore BBB integrity and function following ischaemic damage and how inhibition of NOX2, a main source of vascular oxidative stress, affects the characteristics of BBB established with OECs and HBMECs in ischaemic settings. In vitro models of human BBB were constructed by co-culture of pericytes and astrocytes with either OECs or HBMECs before exposure to oxygen-glucose deprivation (OGD) alone or followed by reperfusion (OGD + R) in the absence or presence of NOX2 inhibitor, gp91ds-tat.

Therapeutic hypothermia augments the restorative effects of PKC-β and Nox2 inhibition on an in vitro model of human blood-brain barrier.

To investigate whether therapeutic hypothermia augments the restorative impact of protein kinase C-β (PKC-β) and Nox2 inhibition on an in vitro model of human blood-brain barrier (BBB). Cells cultured in normoglycaemic (5.5 mM) or hyperglycaemic (25 mM, 6 to 120 h) conditions were treated with therapeutic hypothermia (35 °C) in the absence or presence of a PKC-β inhibitor (LY333531, 0.

The secretome of endothelial progenitor cells: a potential therapeutic strategy for ischemic stroke.

Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as the only pharmacological therapy for stroke patients. However, due to short therapeutic window (4.

MicroRNA: An Emerging Predictive, Diagnostic, Prognostic and Therapeutic Strategy in Ischaemic Stroke.

Stroke continues to be the third-leading cause of death and disability worldwide. The limited availability of diagnostic tools approved therapeutics and biomarkers that help monitor disease progression or predict future events remain as the major challenges in the field of stroke medicine. Hence, attempts to discover safe and efficacious therapeutics and reliable biomarkers are of paramount importance.

Endothelial progenitor cells, potential biomarkers for diagnosis and prognosis of ischemic stroke: protocol for an observational case-control study.

Ischemic stroke is a devastating, life altering event which can severely reduce patient quality of life. Despite years of research there have been minimal therapeutic advances. Endothelial progenitor cells (EPCs), stem cells involved in both vasculogenesis and angiogenesis, may be a potential therapeutic target.