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.

Enhancing siRNA cancer therapy: Multifaceted strategies with lipid and polymer-based carrier systems.

Cancers are increasing in prevalence and many challenges remain for their treatment, such as chemoresistance and toxicity. In this context, siRNA-based therapeutics have many potential advantages for cancer therapies as a result of their ability to reduce or prevent expression of specific cancer-related genes. However, the direct delivery of naked siRNA is hindered by issues like enzymatic degradation, insufficient cellular uptake, and poor pharmacokinetics.

Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine.

DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection.

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.

Charge neutralized poly(β-amino ester) polyplex nanoparticles for delivery of self-amplifying RNA.

Therapeutic self-amplifying RNA (saRNA) is a promising approach for disease treatment, as it can be administered in lower doses than messenger RNA (mRNA) to achieve comparable protein production levels. However, saRNA requires an appropriate delivery vehicle to protect it during transit and facilitate its transfection. A widely-adopted approach has been to use polycations to condense these large anionic macromolecules into polyplex nanoparticles, however their high charge density often elicits cytotoxic effects.

Optimized mucoadhesive niosomal carriers for intranasal delivery of carvedilol: A quality by design approach.

Carvedilol (CV), a β-blocker essential for treating cardiovascular diseases, faces bioavailability challenges due to poor water solubility and first-pass metabolism. This study developed and optimized chitosan (CS)-coated niosomes loaded with CV (CS/CV-NS) for intranasal (IN) delivery, aiming to enhance systemic bioavailability. Utilizing a Quality-by-Design (QbD) approach, the study investigated the effects of formulation variables, such as surfactant type, surfactant-to-cholesterol (CHOL) ratio, and CS concentration, on CS/CV-NS properties.

Social media addiction, escapism and coping strategies are associated with the problematic internet use of adolescents in Türkiye: a multi-center study.

Introduction: The literature highlighted that problematic internet use can have detrimental consequences on individuals' well-being. Social media addiction, escapism and coping skills are closely related to problematic internet use. However, no study has currently examined the relationship between problematic internet use and social media use, escapism and coping skills.

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.

Co-administration of amoxicillin-loaded chitosan nanoparticles and inulin: A novel strategy for mitigating antibiotic resistance and preserving microbiota balance in Helicobacter pylori treatment.

Helicobacter pylori (H. pylori) is a causative agent of various gastrointestinal diseases and eradication mainly relies on antibiotic treatment, with (AMX) being a key component. However, rising antibiotic resistance in H.

Detection of protamine based on competitive adsorption onto the surface of functionalized multi-walled carbon nanotubes.

This study developed an adsorption-based determination system for protamine. A multi-walled carbon nanotube (MWCNT), which is a strong adsorbent, was used. The competitive adsorption process between dyes and protamine formed the basis of the sensor system.

Vascular Ageing: Mechanisms, Risk Factors, and Treatment Strategies.

Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body. Vascular ageing, characterised by vascular stiffness, endothelial dysfunction, increased oxidative stress, chronic low-grade inflammation, and early-stage atherosclerosis, may trigger or exacerbate the development of age-related vascular diseases, which each year contribute to more than 3.8 million deaths in Europe alone and necessitate a better understanding of the mechanisms involved.

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.

Antipsychotics Induced Reproductive Toxicity by Stimulating Oxidative Stress: A Comparative in Vivo and in Silico Study.

The pathophysiological mechanism behind the link between antipsychotic drugs and sexual dysfunction is still unknown. The goal of this research is to compare the potential effects of antipsychotics on the male reproductive system. Fifty rats were randomly assigned into the five groups indicated: Control, Haloperidol, Risperidone, Quetiapine and Aripiprazole.

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.

Could Fetuin-A Be a Biomarker for Autism Spectrum Disorder and Cognitive Developmental Delay?

Early detection of cognitive developmental delay (CDD) and autism spectrum disorder (ASD) is challenging, despite the numerous scientific studies conducted and different therapeutic strategies. Lack of a biomarker for autism is a limiting factor for early diagnosis, which could provide better outcome with early start of therapy. Because of the high serum fetuin-A concentration during intrauterine life, it has been suggested that fetuin-A may have a role in brain development.

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.