Free radicals, vascular damage

Diabetic retinopathy (DR) is a highly hazardous and widespread complication of diabetes mellitus (DM). The accumulated reactive oxygen species (ROS) play a central role in DR development. The aim of this research was to examine the impact and mechanisms of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEV) on regulating ROS and retinal damage in DR. Intravitreal injection of sEV inhibited Cullin3 neddylation, stabilized Nrf2, decreased ROS, reduced retinal inflammation, suppressed Müller gliosis, and mitigated DR...

Cardiovascular diseases (CVDs) are the leading cause of death globally, resulting in a major health burden. Thus, an urgent need exists for exploring effective therapeutic targets to block progression of CVDs and improve patient prognoses. Immune and inflammatory responses are involved in the development of atherosclerosis, ischemic myocardial damage responses and repair, calcification, and stenosis of the aortic valve. These responses can involve both large and small blood vessels throughout the body, leading to increased blood pressure and end-organ damage...

Anomalous vascular endothelium significantly contributes to various cardiovascular diseases. VE-cadherin plays a vital role in governing the endothelial barrier. Krüppel-like factor 4(KLF4), as a transcription factor, which binds the VE-cadherin promoter and enhances its transcription. Tumor necrosis factor receptor-associated factor 7 (TRAF7) is an E3 ubiquitin ligase that has been shown to modulate the degradation of KLF4. H2 S can covalently modify cysteine residues on proteins through S-sulfhydration, thereby influencing the structure and functionality of the target protein...

This editorial contains comments on the article "Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer" in a recent issue of the World Journal of Gastrointestinal Surgery . It pointed out the actuality and importance of the article and focused primarily on the underlying mechanisms making the systemic immune-inflammation index (SII) and geriatric nutritional risk index (GNRI) prediction features valuable. There are few publications on both SII and GNRI together in hepatocellular carcinoma (HCC) and patient prognosis after radical surgery...

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs...

Increasing evidence has revealed the emerging role of ferroptosis in the pathophysiology of type 2 diabetes mellitus (T2DM) and its complications. Platelet-rich plasma (PRP) has been demonstrated to facilitate the healing of T2DM ulcers. However, the mechanism by which PRP repairs T2DM ulcers remains unclear. Here, we sought to investigate the interaction between PRP and ferroptosis in repairing T2DM ulcers. The results showed that the cellular activity, proliferation, and migration of fibroblasts were down-regulated, and the cellular activity and normal function of vascular endothelial cells were impaired in the high glucose environment or under RSL3 conditions (a GSH peroxidase 4 inhibitor and ferroptosis inducer)...

Vascularized composite allotransplantation (VCA) represents a promising reconstructive solution primarily conducted to improve quality of life. However, tissue damage caused by cold-ischemia (CI) storage prior to transplant represents a major factor limiting widespread application. This study investigates the addition of the novel free radical scavenger PrC-210 to UW Organ Preservation Solution (UW Solution) to suppress CI-induced skeletal muscle injury in a rat hind limb amputation model. Lewis rats received systemic perfusion of UW solution +/- PrC-210 (0 mM control, 10 mM, 20 mM, 30 mM, or 40 mM), followed by bilateral transfemoral amputation...

Murine sickle cell disease (SCD) results in damage to multiple organs, likely mediated first by vasculopathy. While the mechanisms inducing vascular damage remain to be determined, nitric oxide bioavailability and sterile inflammation are both considered to play major roles in vasculopathy. Here, we investigate the effects of high mobility group box-1 (HMGB1), a pro-inflammatory damage-associated molecular pattern (DAMP) molecule on endothelial-dependent vasodilation and lung morphometrics, a structural index of damage in sickle (SS) mice...

BACKGROUND: High blood glucose levels in diabetes lead to vascular inflammation which accelerates atherosclerosis. Herein, Morin was orally administered in male Wistar rats, at the dose of 40 mg/kg for 28 days, and on the 27th and 28th day, ISO was administered to designate groups at the dose of 85 mg/kg s.c., to induce myocardial infarction. RESULTS: Free radical generation, including ROS, in diabetes following ISO administration, leads to the activation of both intrinsic and extrinsic pathways of apoptosis...

Vascular diseases, a leading cause of death in human, are strongly associated with pathological damage to blood vessels. The selenoprotein (Sel) have been reported to play important roles in vascular disease. However, the role of SelO in vascular disease has not been conclusively investigated. The present experiment was to investigate the regulatory mechanism of the effect of SelO on the permeability of vascular endothelial. The H.E staining, FITC-Dextran staining, Dil-AC-LDL staining and FITC-WGA staining showed that vascular structure was damaged, and intercellular junctions were disrupted with selenium (Se)-deficient...

Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization...

Heated tobacco products (HTPs) are marketed worldwide as less harmful alternatives to combustible cigarettes; however, their cytotoxic mechanisms in vascular smooth muscle cells are poorly understood. Ferroptosis is defined as iron-dependent cell death caused by the accumulation of lipid peroxidation products. In this study, the cytotoxic effects of nicotine- and tar-free cigarette smoke extracts (CSE) derived from three types of HTPs and the ferroptosis inducer, erastin, on vascular smooth muscle A7r5 cells were compared...

BACKGROUND: Diabetic retinopathy is a progressive disease, and one of the key metabolic abnormalities in the pathogenesis of diabetic retinopathy, mitochondrial damage, is also influenced by the duration of hyperglycemia. Mitochondrial quality control involves a coordination of mitochondrial dynamics, biogenesis and removal of the damaged mitochondria. In diabetes, these processes are impaired, and the damaged mitochondria continue to produce free radicals. Diabetic patients also have high homocysteine and reduced levels of hydrogen sulfide, and hyperhomocysteinemia is shown to exacerbate diabetes-induced mitochondrial damage and worsen their dynamics...

Overloaded glucose levels in several metabolic diseases such as type 2 diabetes (T2D) can lead to mitochondrial dysfunction and enhanced production of reactive oxygen species (ROS). Oxidative stress and altered mitochondrial homeostasis, particularly in the cardiovascular system, contribute to the development of chronic comorbidities of diabetes. Diabetes-associated hyperglycemia and dyslipidemia can directly damage vascular vessels and lead to coronary artery disease or stroke, and indirectly damage other organs and lead to kidney dysfunction, known as diabetic nephropathy...

BACKGROUND: Traumatic brain injury (TBI) is the damage to the brain caused by external blow or jolt to the head or body. TBI secondarily induces cell damage in the hippocampus. This study aimed to investigate effects of resveratrol treatment histological examination and nuclear factor kappa B (NFκB) expression in hippocampus after TBI. MATERIALS AND METHODS: Twenty-four rats were assigned to three groups: sham, TBI and TBI+Resveratol. TBI was conducted by dropping a 50-g weight from a 1-meter height from a tube to the head of animals...

Chronic kidney disease (CKD) patients have a high risk of cardiovascular disease. Indoxyl sulfate (IS) is a uremic toxin that has been shown to inhibit nitric oxide production and cause cell senescence by inducing oxidative stress. High-density lipoprotein (HDL) has a protective effect on the cardiovascular system; however, its impacts on IS-damaged endothelial cells are still unknown. This study aimed to explore the effects of exogenous supplement of HDL on vascular endothelial cells in a uremia-mimic environment...

Inflammation is a multifaceted biological reaction to a wide range of stimuli, and it has been linked to the onset and progression of chronic diseases such as heart disease, cancer, and diabetes. Inflammatory markers found in the blood, including C-reactive protein, serum amyloid A, fibrinogen, plasma viscosity, erythrocyte sedimentation rate, interleukin-6, and soluble adhesion molecules (like intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), are risk factors for cardiovascular diseases such as coronary heart disease, stroke, and peripheral arterial disease...

Glutamate induced damage to retinal ganglion cells (RGCs) requires tight physiological regulation of the N-methyl-D-aspartate (NMDA) receptors. Previously, studies have demonstrated the neuroprotective abilities of antioxidants like coenzyme Q10 (CoQ10 ) and vitamin E analogs like α-tocopherol against neuropathies resulting from NMDA insult, but have failed to shed light on the effect of CoQ10 and trolox, a hydrophilic analog of vitamin E, on glaucomatous neurodegeneration. In the current study, we wanted to investigate whether the combined effect of trolox with CoQ10 could alleviate NMDA-induced death of retinal cells while also trying to elucidate the underlying mechanism in relation to the yet unexplained role of vascular endothelial growth factor (VEGF) in NMDA-mediated excitotoxicity...

The ability and facility of magnesium (Mg2+) and zinc (Zn2+) to interact with phosphate ions confer them the characteristics of essential trace elements. Trace elements are extremely necessary for the basic nucleic acid chemistry of cells of all known living organisms. More than 300 enzymes require zinc and magnesium ions for their catalytic actions, including all the enzymes involved in the synthesis of ATP. In addition, enzymes such as isomerases, oxidoreductases, lyases, transferases, ligases and hydrolases that use other nucleotides to synthesize DNA and RNA require magnesium and zinc...

Volumetric muscle loss (VML) is a condition that results in the extensive loss of 20 % or more of skeletal muscle due to trauma or tumor ablation, leading to severe functional impairment and permanent disability. The current surgical interventions have limited functional regeneration of skeletal muscle due to the compromised self-repair mechanism. Melatonin has been reported to protect skeletal muscle from exercise-induced oxidative damage and holds great potential to treat muscle diseases. In this study, we hypothesize that melatonin can enhance myoblast differentiation and promote effective recovery of skeletal muscle following VML...