Search results for "hate"
showing 10 items of 2099 documents
Modulating Oxidant Levels to Promote Healthy Aging
2020
Significance: Free radicals although originally thought of as damaging molecules, inevitable side effects of the utilization of oxygen by cells, are now considered as signals that by modifying, among others, the thiol-disulfide balance regulate many cell processes from metabolism to cell cycle. Recent Advances: This review discusses the importance of the modulation of the oxidant levels through physiological strategies such as physical exercise or genetic manipulations such as the overexpression of antioxidant enzymes, in the promotion of healthy aging. Critical Issues: We have divided the review into five different sections. In the first two sections of the article "Oxidants are signals" a…
Overexpression of glucose 6 phosphate dehydrogenase preserves mouse pancreatic beta cells function until late in life.
2021
NAD(P)H donates electrons for reductive biosynthesis and antioxidant defense across all forms of life. Glucose-6- phosphate dehydrogenase (G6PD) is a critical enzyme to provide NADPH. G6PD deficiency is present in more than 400 million people worldwide. This enzymopathy provides protection against malaria but sensitizes cells to oxidative stressors. Oxidative stress has been involved in the pathogenesis of the diabetic complications and several studies have provided evidences of a link between G6PD deficiency and type 2 diabetes (T2D). We hypothesized that a moderate overexpression of G6PD (G6PD-Tg) could protect β-cells from age-associated oxidative stress thus reducing the risk of develop…
Abacavir Increases Purinergic P2X7 Receptor Activation by ATP: Does a Pro-inflammatory Synergism Underlie Its Cardiovascular Toxicity?
2021
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Safe neoadjuvant trastuzumab-based treatment in HER2 + inflammatory early breast cancer in a glucose 6-phosphate dehydrogenase-deficient postmenopaus…
2019
Introduction Glucose 6-phosphate dehydrogenase (G6PD) is a basic antioxidant pathway for erythrocytes, being its deficiency the most common gene mutation worldwide. As breast cancer is one of the most frequent tumors, many of these patients may present with G6PD deficiency prior treatment without notice. Case report We present the case of a woman deficient for G6PD with the diagnosis of Stage IIIB (cT4d cN1 cM0) HER2-enriched early breast cancer. Management and outcome The patient underwent neoadjuvance with trastuzumab and anthracycline-free chemotherapy, based on docetaxel (75 mg/m2, 120 mg) and carboplatin (AUC 5, 560 mg). She did not present hemolytic crisis and no blood transfusions we…
Biostimulation proved to be the most efficient method in the comparison of in situ soil remediation treatments after a simulated oil spill accident
2016
The use of in situ techniques in soil remediation is still rare in Finland and most other European countries due to the uncertainty of the effectiveness of the techniques especially in cold regions and also due to their potential side effects on the environment. In this study, we compared the biostimulation, chemical oxidation, and natural attenuation treatments in natural conditions and pilot scale during a 16-month experiment. A real fuel spill accident was used as a model for experiment setup and soil contamination. We found that biostimulation significantly decreased the contaminant leachate into the water, including also the non-aqueous phase liquid (NAPL). The total NAPL leachate was …
Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis
2018
Summary Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional respons…
Polyphosphate as a metabolic fuel in Metazoa: A foundational breakthrough invention for biomedical applications
2015
In animals, energy-rich molecules like ATP are generated in the intracellular compartment from metabolites, e.g. glucose, taken up by the cells. Recent results revealed that inorganic polyphosphates (polyP) can provide an extracellular system for energy transport and delivery. These polymers of multiple phosphate units, linked by high-energy phosphoanhydride bonds, use blood platelets as transport vehicles to reach their target cells. In this review it is outlined how polyP affects cell metabolism. It is discussed that polyP influences cell activity in a dual way: (i) as a metabolic fuel transferring metabolic energy through the extracellular space; and (ii) as a signaling molecule that amp…
Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition
2017
Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein-coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin aIIbb3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies. We ap…
Morphogenetically-Active Barrier Membrane for Guided Bone Regeneration, Based on Amorphous Polyphosphate
2017
We describe a novel regeneratively-active barrier membrane which consists of a durable electrospun poly(ε-caprolactone) (PCL) net covered with a morphogenetically-active biohybrid material composed of collagen and inorganic polyphosphate (polyP). The patch-like fibrous collagen structures are decorated with small amorphous polyP nanoparticles (50 nm) formed by precipitation of this energy-rich and enzyme-degradable (alkaline phosphatase) polymer in the presence of calcium ions. The fabricated PCL-polyP/collagen hybrid mats are characterized by advantageous biomechanical properties, such as enhanced flexibility and stretchability with almost unaltered tensile strength of the PCL net. The pol…
Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ
2018
Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The r…