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Open accessJournal ArticleDOI: 10.1038/S41467-021-21714-2

Catalytic activity tunable ceria nanoparticles prevent chemotherapy-induced acute kidney injury without interference with chemotherapeutics.

04 Mar 2021-Nature Communications (Nature Publishing Group)-Vol. 12, Iss: 1, pp 1436-1436
Abstract: Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H+ that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients. Reactive oxygen species management is a practical strategy that can reduce the risk of chemotherapy-induced acute kidney injury, but at the cost of chemotherapeutic efficacy. Here the authors report catalytic activity tunable ceria nanoparticles as context-dependent reactive oxygen species scavengers, which can prevent chemotherapy-induced acute kidney injury without interfering with chemotherapeutic agents.

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Topics: Acute kidney injury (51%)
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15 results found


Open accessBook
01 Jan 2013-
Abstract: Chapter 1 Transmissible Spongiform Encephalopathy: from the High Middle Ages to Daniel Carlton Gajdusek Paul Brown Chapter 2 The Rich Chemistry of the Copper and Zinc Sites in Cellular Prion Protein Glenn L. Millhauser Chapter 3 Role of Cellular Prion Protein in the Amyloid-ss Oligomer Pathophysiology of Alzheimer's Disease Adam C. Kaufman, Stephen M. Strittmatter Chapter 4 Cellular Prion Protein and Cancers Wei Xin, Man-sun Sy, Chaoyang Li Chapter 5 Insoluble Cellular Prion Protein Wen-Quan Zou Chapter 6 Protein Misfolding Cyclic Amplification Fabio Moda, Sandra Pritzkow, Claudio Soto Chapter 7 Cofactor Involvement in Prion Propagation Surachai Supattapone, Michael B. Miller Chapter 8 Prion Protein Conversion and Lipids Jiyan Ma Chapter 9 New Perspectives on Prion Conversion: Introducing a Mechanism of Deformed Templating Ilia V. Baskakov Chapter 10 Infectious and Pathogenic Forms of Prion Protein Emiliano Biasini, David A. Harris Chapter 11 Cellular Mechanisms of Propagation and Clearance Hermann M. Schatzl Chapter 12 Molecular Mechanisms Encoding Quantitative and Qualitative Traits of Prion Strains Jiri G. Safar Chapter 13 Modeling the Cell Biology of Prions Richard Rubenstein, Robert B. Petersen Chapter 14 Prion Strain Interference Charles R. Schutt, Ronald A. Shikiya, Jason C. Bartz Chapter 15 Introduction to Yeast and Fungal Prions Reed B. Wickner Chapter 16 Yeast Prions are Pathogenic, in-register Parallel Amyloids Reed B. Wickner, Herman K. Edskes, David A. Bateman, Amy C. Kelly, Anton Gorkovskiy

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285 Citations


Open accessJournal ArticleDOI: 10.3390/NANO11092259
31 Aug 2021-Nanomaterials
Abstract: Ceria (CeO2) nanostructures are well-known in catalysis for energy and environmental preservation and remediation. Recently, they have also been gaining momentum for biological applications in virtue of their unique redox properties that make them antioxidant or pro-oxidant, depending on the experimental conditions and ceria nanomorphology. In particular, interest has grown in the use of biotemplates to exert control over ceria morphology and reactivity. However, only a handful of reports exist on the use of specific biomolecules to template ceria nucleation and growth into defined nanostructures. This review focusses on the latest advancements in the area of biomolecular templates for ceria nanostructures and existing opportunities for their (bio)applications.

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4 Citations


Open access
15 Oct 2015-
Abstract: Background & aim: Cyclophosphamide, an alkylating agent used in the treatment of cancer that has many side effects on different organs, including the gonads .The purpose of this study was to investigate the effects of an antioxidant Ellagic acid on cyclophosphamide -induced toxicity in rat fetal ovarian tissue. Methods: Forty two pregnant female Wistar rats weighing 250-200 gr were randomly divided into seven groups.The first, second, third, fourth, fifth and sixth 5 mg/ kg cyclophosphamide on days 1, 13 and 18 were given intraperitoneal remote pregnancy .The fourth, fifth and sixth groups hour after receiving cyclophosphamide, Ellagic acid (10 mg/kg) has received in the course of pregnancy.Control groups and seven group (normal) during pregnancy daily orally received 0.5 mL of saline. After postpartum, Neonatal rats were anesthetized with ether. Animals were dissects, then Ovaries were removed and transferred to 10% formalin solution. After tissue processing, tissue sections were prepared and H&E stained.Data were analyzed by SPSSsoftware and Oneway ANOVA test. Results: The groups that were exposed to cyclophosphamide ovarian mean of diameter, primordial follicle diameter and number of follicular cell of primordialin control group compared to ellagic acid treatments showed a significant decrease. Conclusion: The results showed that Ellagic acid due to its antioxidant properties could reduce the harmful effects caused by cyclophosphamide in the fetal ovary.

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Topics: Ellagic acid (59%), Toxicity (53%)

2 Citations


Open accessJournal ArticleDOI: 10.1007/S00467-021-05121-9
Abstract: The proximal tubule (PT) reabsorbs most of the glomerular filtrate and plays an important role in the uptake, metabolism and excretion of xenobiotics. Some therapeutic drugs are harmful to the PT, and resulting nephrotoxicity is thought to be responsible for approximately 1 in 6 of cases of children hospitalized with acute kidney injury (AKI). Clinically, PT dysfunction leads to urinary wasting of important solutes normally reabsorbed by this nephron segment, leading to systemic complications such as bone demineralization and a clinical scenario known as the renal Fanconi syndrome (RFS). While PT defects can be diagnosed using a combination of blood and urine markers, including urinary excretion of low molecular weight proteins (LMWP), standardized definitions of what constitutes clinically significant toxicity are lacking, and identifying which patients will go on to develop progressive loss of kidney function remains a major challenge. In addition, much of our understanding of cellular mechanisms of drug toxicity is still limited, partly due to the constraints of available cell and animal models. However, advances in new and more sophisticated in vitro models of the PT, along with the application of high-content analytical methods that can provide readouts more relevant to the clinical manifestations of nephrotoxicity, are beginning to extend our knowledge. Such technical progress should help in discovering new biomarkers that can better detect nephrotoxicity earlier and predict its long-term consequences, and herald a new era of more personalized medicine.

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Topics: Fanconi syndrome (56%), Nephrotoxicity (53%), Acute kidney injury (52%)

2 Citations


Open accessJournal ArticleDOI: 10.1038/S41598-021-94327-W
19 Jul 2021-Scientific Reports
Abstract: This contribution presents the biosynthesis, physiochemical properties, toxicity and photocatalytic activity of biogenic CeO2 NPs using, for the first time, marine oyster extract as an effective and rich source of bioreducing and capping/stabilizing agents in a one-pot recipe. CeO2 NPs formation was initially confirmed through the color change from light green to pale yellow and subsequently, their corresponding absorption peak was spectroscopically determined at 310 nm with an optical band-gap of 4.67 eV using the DR-UV technique. Further, XRD and Raman analyses indicated that nanoceria possessed face-centered cubic arrangements without any impurities, having an average crystallite size of 10 nm. TEM and SEM results revealed that biogenic CeO2 NPs was approximately spherical in shape with a median particle size of 15 ± 1 nm. The presence of various bioorganic substances on the surface of nanoparticles was deduced by FTIR and TGA results. It is found that marine-based nanoceria shows no cytotoxic effect on the normal cell, thus indicating their enhanced biocompatibility and biosafety to living organisms. Environmentally, due to energy band gap, visible light-activated CeO2 nanocatalyst revealed superior photocatalytic performance on degradation of methylene blue pollutant with removal rate of 99%. Owing to the simplicity, cost-effectiveness, and environmentally friendly nature, this novel marine biosynthetic route paves the way for prospective applications of nanoparticles in various areas.

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1 Citations


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71 results found


Open accessJournal ArticleDOI: 10.1152/PHYSREV.00044.2005
Karen Bedard1, Karl-Heinz KrauseInstitutions (1)
Abstract: For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

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Topics: NADPH Oxidase 1 (67%), NOX4 (64%), NOX1 (63%) ... show more

5,183 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.294.7.813
Shigehiko Uchino1, John A. Kellum2, Rinaldo Bellomo3, Gordon S. Doig4  +9 moreInstitutions (11)
17 Aug 2005-JAMA
Abstract: ContextAlthough acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world.ObjectivesTo determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes.Design, Setting, and PatientsProspective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries.Main Outcome MeasuresOccurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality.ResultsOf 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03).ConclusionIn this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.

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Topics: Severity of illness (54%), Intensive care unit (52%), Hemodialysis (51%) ... show more

3,357 Citations


Open accessJournal ArticleDOI: 10.1038/NATURE10189
07 Jul 2011-Nature
Abstract: Reactive oxygen species (ROS) are mutagenic and may thereby promote cancer. Normally, ROS levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors and is predominantly regulated by the transcription factor Nrf2 (also known as Nfe2l2) and its repressor protein Keap1 (refs 2-5). In contrast to the acute physiological regulation of Nrf2, in neoplasia there is evidence for increased basal activation of Nrf2. Indeed, somatic mutations that disrupt the Nrf2-Keap1 interaction to stabilize Nrf2 and increase the constitutive transcription of Nrf2 target genes were recently identified, indicating that enhanced ROS detoxification and additional Nrf2 functions may in fact be pro-tumorigenic. Here, we investigated ROS metabolism in primary murine cells following the expression of endogenous oncogenic alleles of Kras, Braf and Myc, and found that ROS are actively suppressed by these oncogenes. K-Ras(G12D), B-Raf(V619E) and Myc(ERT2) each increased the transcription of Nrf2 to stably elevate the basal Nrf2 antioxidant program and thereby lower intracellular ROS and confer a more reduced intracellular environment. Oncogene-directed increased expression of Nrf2 is a new mechanism for the activation of the Nrf2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-Ras(G12D) and B-Raf(V619E), and in human pancreatic cancer. Furthermore, genetic targeting of the Nrf2 pathway impairs K-Ras(G12D)-induced proliferation and tumorigenesis in vivo. Thus, the Nrf2 antioxidant and cellular detoxification program represents a previously unappreciated mediator of oncogenesis.

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Topics: Cellular detoxification (57.99%), Transcription factor (55%), Carcinogenesis (54%) ... show more

1,520 Citations


Journal ArticleDOI: 10.1016/S0140-6736(11)61454-2
25 Aug 2012-The Lancet
Abstract: Acute kidney injury (formerly known as acute renal failure) is a syndrome characterised by the rapid loss of the kidney's excretory function and is typically diagnosed by the accumulation of end products of nitrogen metabolism (urea and creatinine) or decreased urine output, or both. It is the clinical manifestation of several disorders that affect the kidney acutely. Acute kidney injury is common in hospital patients and very common in critically ill patients. In these patients, it is most often secondary to extrarenal events. How such events cause acute kidney injury is controversial. No specific therapies have emerged that can attenuate acute kidney injury or expedite recovery; thus, treatment is supportive. New diagnostic techniques (eg, renal biomarkers) might help with early diagnosis. Patients are given renal replacement therapy if acute kidney injury is severe and biochemical or volume-related, or if uraemic-toxaemia-related complications are of concern. If patients survive their illness and do not have premorbid chronic kidney disease, they typically recover to dialysis independence. However, evidence suggests that patients who have had acute kidney injury are at increased risk of subsequent chronic kidney disease.

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Topics: Acute kidney injury (75%), Renal replacement therapy (74%), Kidney disease (74%) ... show more

1,401 Citations


Journal ArticleDOI: 10.1038/NNANO.2006.170
Zhuang Liu1, Weibo Cai1, Lina He1, Nozomi Nakayama1  +4 moreInstitutions (1)
Abstract: Single-walled carbon nanotubes (SWNTs) exhibit unique size, shape and physical properties1,2,3 that make them promising candidates for biological applications. Here, we investigate the biodistribution of radio-labelled SWNTs in mice by in vivo positron emission tomography (PET), ex vivo biodistribution and Raman spectroscopy. It is found that SWNTs that are functionalized with phospholipids bearing polyethylene-glycol (PEG) are surprisingly stable in vivo. The effect of PEG chain length on the biodistribution and circulation of the SWNTs is studied. Effectively PEGylated SWNTs exhibit relatively long blood circulation times and low uptake by the reticuloendothelial system (RES). Efficient targeting of integrin positive tumour in mice is achieved with SWNTs coated with PEG chains linked to an arginine–glycine–aspartic acid (RGD) peptide. A high tumour accumulation is attributed to the multivalent effect of the SWNTs. The Raman signatures of SWNTs are used to directly probe the presence of nanotubes in mice tissues and confirm the radio-label-based results.

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Topics: Biodistribution (54%)

1,370 Citations


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