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Vascular response to free radicals

Kwanghee Kim, Philip A Watson, Souhil Lebdai, Sylvia Jebiwott, Alexander Somma, Stephen P La Rosa, Dipti Mehta, Katie S Murray, Hans G Lilja, David Ulmert, Sebastien Monette, Avigdor J Scherz, Jonathan Coleman
PURPOSE: WST11 vascular targeted photodynamic therapy (VTP) is a local ablation approach relying upon rapid, free radical-mediated destruction of tumor vasculature. A phase III trial showed that VTP significantly reduced disease progression when compared to active surveillance in patients with low-risk prostate cancer (PCa). The aim of this study was to identify a druggable pathway that could be combined with VTP to improve its efficacy and applicability to higher risk PCa tumors. EXPERIMENTAL DESIGN: Transcriptome analysis of VTP treated tumors (LNCaP-AR xenografts) was used to identify a candidate pathway for combination therapy...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zhaobin Cai, Tingting Shi, Rangxiao Zhuang, Hongying Fang, Xiaojie Jiang, Yidan Shao, Hongping Zhou
With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane...
February 2018: Experimental and Therapeutic Medicine
Rheal A Towner, D Saunders, N Smith, W Towler, M Cruz, S Do, J E Maher, K Whitaker, M Lerner, K A Morton
Sepsis-associated encephalopathy (SAE) induces neuroinflammation, which is associated with cognitive impairment (CI). CI is also correlated with aging. We used contrast-enhanced magnetic resonance imaging (MRI), perfusion MRI, and MR spectroscopy to assess long-term alterations in BBB permeability, microvascularity, and metabolism, respectively, in a rat lipopolysaccharide-induced SAE model. Free radical-targeted molecular MRI was used to detect brain radical levels at 24 h and 1 week post-LPS injection. CE-MRI showed increased Gd-DTPA uptake in LPS rat brains at 24 h in cerebral cortex, hippocampus, thalamus, and perirhinal cortex regions...
February 7, 2018: GeroScience
Forrest H Nielsen
Animal studies have shown that magnesium deficiency induces an inflammatory response that results in leukocyte and macrophage activation, release of inflammatory cytokines and acute-phase proteins, and excessive production of free radicals. Animal and in vitro studies indicate that the primary mechanism through which magnesium deficiency has this effect is through increasing cellular Ca2+, which is the signal that results in the priming of cells to give the inflammatory response. Primary pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-1; the messenger cytokine IL-6; cytokine responders E-selectin, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1; and acute-phase reactants C-reactive protein and fibrinogen have been determined to associate magnesium deficiency with chronic low-grade inflammation (inflammatory stress)...
2018: Journal of Inflammation Research
Florian Simon, Alexander Oberhuber, Nikolaos Floros, Albert Busch, Markus Udo Wagenhäuser, Hubert Schelzig, Mansur Duran
Acute ischemia of an extremity occurs in several stages, a lack of oxygen being the primary contributor of the event. Although underlying patho-mechanisms are similar, it is important to determine whether it is an acute or chronic event. Healthy tissue does not contain enlarged collaterals, which are formed in chronically malperfused tissue and can maintain a minimum supply despite occlusion. The underlying processes for enhanced collateral blood flow are sprouting vessels from pre-existing vessels (via angiogenesis) and a lumen extension of arterioles (via arteriogenesis)...
January 26, 2018: International Journal of Molecular Sciences
Miguel Aguilar, Alejandro González-Candia, Jorge Rodríguez, Catalina Carrasco-Pozo, Daniel Cañas, Claudio García-Herrera, Emilio A Herrera, Rodrigo L Castillo
More than 140 million people live and works (in a chronic or intermittent form) above 2500 m worldwide and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 55,000 persons work in high altitude shifts, where stays at lowlands and interspersed with working stays at highlands. Acute exposure to high altitude has been shown to induce oxidative stress in healthy human lowlanders, due to an increase in free radical formation and a decrease in antioxidant capacity. However, in animal models, intermittent hypoxia (IH) induce preconditioning, like responses and cardioprotection...
January 26, 2018: International Journal of Molecular Sciences
Xianshuang Chen, Hao Gu, Zhonglin Lyu, Xiaoli Liu, Lei Wang, Hong Chen, John L Brash
Blood compatibility is a long sought-after goal in biomaterials research, but remains an elusive one, and in spite of extensive work in this area, there is still no definitive information on the relationship between material properties and blood responses such as coagulation and thrombus formation. Materials modified with heparin-mimicking polymers have shown promise and indeed may be seen as comparable to materials modified with heparin itself. In this work, heparin was conceptualized as consisting of two major structural elements: saccharide- and sulfonate-containing units, and polymers based on this concept were developed...
January 10, 2018: ACS Applied Materials & Interfaces
Lucia Crascì, Venera Cardile, Giusy Longhitano, Francesco Nanfitò, Annamaria Panico
Background Inflammation is a dynamic process that occur on vascularized tissue in response to different stimuli causing cell injury and tissue degeneration. Reactive oxygen and nitrogen species (ROS and RNS) and advanced glycation end products (AGEs) have a key mediatory role in the development and progression of degenerative tissue process. The bioflavonoids possess a broad-spectrum of pharmacological activities. Their capability is related to their chemical structure. Methods In this study we evaluated and compare antioxidant, anti-glycative and anti-degenerative actions of two flavones apigenin and luteolin and a flavonol quercetin, in function of their hydroxyl groups arrangement...
November 6, 2017: Drug Research
Hermann Haller, Linong Ji, Klaus Stahl, Anna Bertram, Jan Menne
Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40-50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues...
2017: BioMed Research International
Krzysztof M Krawczyk, Jennifer Hansson, Helén Nilsson, Katarzyna K Krawczyk, Karl Swärd, Martin E Johansson
BACKGROUND: Caveolae are membrane invaginations measuring 50-100 nm. These organelles, composed of caveolin and cavin proteins, are important for cellular signaling and survival. Caveolae play incompletely defined roles in human kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described previously, but the responsible mechanism remains to be defined. METHODS: Healthy and atrophying human kidneys were stained for caveolar proteins, (caveolin 1-3 and cavin 1-4) and examined by electron microscopy...
October 24, 2017: BMC Nephrology
Hock Eng Khoo, Azrina Azlan, Sou Teng Tang, See Meng Lim
Anthocyanins are colored water-soluble pigments belonging to the phenolic group. The pigments are in glycosylated forms. Anthocyanins responsible for the colors, red, purple, and blue, are in fruits and vegetables. Berries, currants, grapes, and some tropical fruits have high anthocyanins content. Red to purplish blue-colored leafy vegetables, grains, roots, and tubers are the edible vegetables that contain a high level of anthocyanins. Among the anthocyanin pigments, cyanidin-3-glucoside is the major anthocyanin found in most of the plants...
2017: Food & Nutrition Research
Xinyu Yang, Yang Li, Yanda Li, Xiaomeng Ren, Xiaoyu Zhang, Dan Hu, Yonghong Gao, Yanwei Xing, Hongcai Shang
Atherogenesis, the formation of atherosclerotic plaques, is a complex process that involves several mechanisms, including endothelial dysfunction, neovascularization, vascular proliferation, apoptosis, matrix degradation, inflammation, and thrombosis. The pathogenesis and progression of atherosclerosis are explained differently by different scholars. One of the most common theories is the destruction of well-balanced homeostatic mechanisms, which incurs the oxidative stress. And oxidative stress is widely regarded as the redox status realized when an imbalance exists between antioxidant capability and activity species including reactive oxygen (ROS), nitrogen (RNS) and halogen species, non-radical as well as free radical species...
2017: Frontiers in Physiology
Dongbo Guo, Shuting Xu, Nan Wang, Huangyong Jiang, Yu Huang, Xin Jin, Bai Xue, Chuan Zhang, Xinyuan Zhu
Photodynamic therapy (PDT) induced hypoxia can significantly upregulate the expression of vascular endothelial growth factor (VEGF) at the tumor-stromal interface, resulting in a promoted angiogenesis. Thus, an angiogenesis vessel-targeting nanoparticle (AVT-NP) consisting of photosensitizer, angiogenic vessel-targeting peptide, and bioreductive prodrug is developed for a chemo-photo synergistic cancer therapy, with which anti-cancer effect is achieved first by PDT and immediately followed with hypoxia-activated cytotoxic free radicals...
November 2017: Biomaterials
Leonardo B de Paula, Fernando L Primo, Antonio C Tedesco
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most recurrent and malignant astrocytic glioma found in adults. Biologically, GBMs are highly aggressive tumors that often show diffuse infiltration of the brain parenchyma, making complete surgical resection difficult. GBM is not curable with surgery alone because tumor cells typically invade the surrounding brain, rendering complete resection unsafe. Consequently, present-day therapy for malignant glioma remains a great challenge. The location of the invasive tumor cells presents several barriers to therapeutic delivery...
October 2017: Biophysical Reviews
Tobias Nilsson, Jan F Gielis, Alexis Slama, Christoffer Hansson, Andreas Wallinder, Sven-Erik Ricksten, Göran Dellgren
BACKGROUND: Two clinically used strategies for ex vivo lung perfusion (EVLP) were compared in a porcine model with respect to lung function, metabolism, inflammatory response, oxidative stress, and cell viability. METHODS: Porcine lungs (n = 20) were preserved, harvested, and kept cooled for 2 hours. After randomization, EVLP was performed using a cellular perfusate and open left atrium (COA group) or an acellular perfusate and a closed left atrium (ACA group). Oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen), compliance, dead space, weight, and perfusate oncotic pressure were registered before and after a 4-hour period of reconditioning...
July 8, 2017: Journal of Heart and Lung Transplantation
E Belcastro, W Wu, I Fries-Raeth, A Corti, A Pompella, P Leroy, I Lartaud, C Gaucher
Among S-nitrosothiols showing reversible binding between NO and -SH group, S-nitrosoglutathione (GSNO) represents potential therapeutics to treat cardiovascular diseases (CVD) associated with reduced nitric oxide (NO) availability. It also induces S-nitrosation of proteins, responsible for the main endogenous storage form of NO. Although oxidative stress parallels CVD development, little is known on the ability of GSNO to restore NO supply and storage in vascular tissues under oxidative stress conditions. Aortic rat smooth muscle cells (SMC) were stressed in vitro with a free radical generator (2,2'-azobis(2-amidinopropane) dihydrochloride, AAPH)...
July 23, 2017: Nitric Oxide: Biology and Chemistry
Rogério Faustino Ribeiro Júnior, Vinicius Bermond Marques, Dieli Oliveira Nunes, Ivanita Stefanon, Leonardo Dos Santos
Iron overload leads to excessive free radical formation and induces cardiovascular dysfunction. Thus, our aim was to investigate the structural and endothelial modulation of vascular tone induced by chronic iron overload in mesenteric arteries. Rats were divided into two groups: the control (vehicle) group and the group treated with iron dextran for 28days (100mg/kg, 5days a week). Chronic iron overload altered the following morpho-physiological parameters of third-order mesenteric resistance arteries: decreased lumen and external diameters; increased wall/lumen ratio and wall thickness; decreased distensibility and increased stiffness; and increased pulse wave velocity...
September 5, 2017: Toxicology Letters
J Deweirdt, J F Quignard, B Crobeddu, A Baeza-Squiban, J Sciare, A Courtois, S Lacomme, E Gontier, B Muller, J P Savineau, R Marthan, C Guibert, I Baudrimont
Recent studies have revealed that particulate matter (PM) exert deleterious effects on vascular function. Pulmonary artery endothelial cells (HPAEC), which are involved in the vasomotricity regulation, can be a direct target of inhaled particles. Modifications in calcium homeostasis and oxidative stress are critical events involved in the physiopathology of vascular diseases. The objectives of this study were to assess the effects of PM2.5 on oxidative stress and calcium signaling in HPAEC. Different endpoints were studied, (i) intrinsic and intracellular production of reactive oxygen species (ROS) by the H2 DCF-DA probe, (ii) intrinsic, intracellular and mitochondrial production of superoxide anion (O2 - ) by electronic paramagnetic resonance spectroscopy and MitoSOX probe, (iii) reactive nitrosative species (RNS) production by Griess reaction, and (vi) calcium signaling by the Fluo-4 probe...
December 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Enrico Gugliandolo, Roberta Fusco, Flavia Biundo, Ramona D'Amico, Filippo Benedetto, Rosanna Di Paola, Salvatore Cuzzocrea
Acute and chronic inflammation responses are important risk factors for vascular remodeling processes such as in atherosclerosis, arteriosclerosis and restenosis. Inflammation and oxidative stress in the intimal region after vascular damage are a key event in the development of neointimal hyperplasia. In this study, we used this model of vascular damage, which involves the complete ligature of the left carotid artery for 14days, to observe the role of N-palmitoylethanolamine in combination with Polydatin at the dose of 30mg/kg, on regulation of inflammatory process, and oxidative stress...
July 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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