scholarly journals Nanosonosensitizers With Ultrasound-Induced Reactive Oxygen Species Generation for Cancer Sonodynamic Immunotherapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Danling Cheng ◽  
Xiaoying Wang ◽  
Xiaojun Zhou ◽  
Jingchao Li
Keyword(s):  
Reactive Oxygen Species ◽  
Therapeutic Strategy ◽  
Tumor Regression ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Combinational Therapy ◽  
Immunotherapy Of Cancer ◽  
Current Concerns

Immunotherapy is a promising therapeutic strategy for cancer, while it has been demonstrated to encounter the issues of low immune responses and underlying immune-related adverse events. The sonodynamic therapy (SDT) that utilizes sonosensitizers to produce reactive oxygen species (ROS) triggered by ultrasound (US) stimulation can be used to ablate tumors, which also leads to the induction of immunogenic cell death (ICD), thus achieving SDT-induced immunotherapy. Further combination of SDT with immunotherapy is able to afford enhanced antitumor immunity for tumor regression. In this mini review, we summarize the recent development of nanosonosensitizers with US-induced ROS generation for cancer SDT immunotherapy. The uses of nanosonosensitizers to achieve SDT-induced immunotherapy, combinational therapy of SDT with immunotherapy, and combinational therapy of SDT with multiple immunotherapies are briefly introduced. Furthermore, the current concerns and perspectives for the development and further clinical applications of these nanosonosensitizers for SDT-combined immunotherapy of cancer are discussed.

Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: A novel antioxidative mechanism

2007 ◽  
Vol 97 (01) ◽  
pp. 88-98 ◽  
Author(s):  
Christina Barja-Fidalgo ◽  
Vany Nascimento-Silva ◽  
Maria Arruda ◽  
Iolanda Fierro
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Ros Generation ◽  
Oxygen Species ◽  
Lipoxin A4 ◽  
Pre Treatment

SummaryLipoxins and their aspirin-triggered carbon-15 epimers have emerged as mediators of key events in endogenous anti-inflammation and resolution. However, the implication of these novel lipid mediators on cardiovascular diseases such as hypertension, atherosclerosis, and heart failure has not been investigated. One of the major features shared by these pathological conditions is the increased production of reactive oxygen species (ROS) generated by vascular NAD(P)H oxidase activation. In this study, we have examined whether an aspirin-triggered lipoxin A4 analog (ATL-1) modulates ROS generation in endothelial cells (EC). Pre-treatment of EC with ATL-1 (1–100 nM) completely blocked ROS production triggered by different agents, as assessed by dihydrorhodamine 123 and hydroethidine. Furthermore, ATL-1 inhibited the phosphorylation and translocation of the cytosplamic NAD(P)H oxidase subunit p47phox to the cell membrane as well as NAD(P)H oxidase activity. Western blot and immunofluorescence microscopy analyses showed that ATL-1 (100 nM) impaired the redox-sensitive activation of the transcriptional factor NF-κB, a critical step in several events associated to vascular pathologies. These results demonstrate that ATL-1 suppresses NAD(P)H oxidase-mediated ROS generation in EC, strongly indicating that lipoxins may play a protective role against the development and progression of cardiovascular diseases.

scholarly journals Plasmonic Hot-Electron Reactive Oxygen Species Generation: Fundamentals for Redox Biology

2020 ◽  
Vol 8 ◽  
Author(s):  
Elisa Carrasco ◽  
Juan Carlos Stockert ◽  
Ángeles Juarranz ◽  
Alfonso Blázquez-Castro
Keyword(s):  
Reactive Oxygen Species ◽  
Near Infrared ◽  
Chemical Reactivity ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Hot Electron ◽  
Redox Biology

For decades, the possibility to generate Reactive Oxygen Species (ROS) in biological systems through the use of light was mainly restricted to the photodynamic effect: the photoexcitation of molecules which then engage in charge- or energy-transfer to molecular oxygen (O2) to initiate ROS production. However, the classical photodynamic approach presents drawbacks, like per se chemical reactivity of the photosensitizing agent or fast molecular photobleaching due to in situ ROS generation, to name a few. Recently, a new approach, which promises many advantages, has entered the scene: plasmon-driven hot-electron chemistry. The effect takes advantage of the photoexcitation of plasmonic resonances in metal nanoparticles to induce a new cohort of photochemical and redox reactions. These metal photo-transducers are considered chemically inert and can undergo billions of photoexcitation rounds without bleaching or suffering significant oxidative alterations. Also, their optimal absorption band can be shape- and size-tailored in order to match any of the near infrared (NIR) biological windows, where undesired absorption/scattering are minimal. In this mini review, the basic mechanisms and principal benefits of this light-driven approach to generate ROS will be discussed. Additionally, some significant experiments in vitro and in vivo will be presented, and tentative new avenues for further research will be advanced.

scholarly journals The Involvement of the Tyrosine Kinase c-Src in the Regulation of Reactive Oxygen Species Generation Mediated by NADPH Oxidase-1

2008 ◽  
Vol 19 (7) ◽  
pp. 2984-2994 ◽  
Author(s):  
Davide Gianni ◽  
Ben Bohl ◽  
Sara A. Courtneidge ◽  
Gary M. Bokoch
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Tyrosine Kinase ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Tumor Formation ◽  
Ros Generation ◽  
Oxygen Species ◽  
Human Colon Carcinoma Cell ◽  
Kinase C

NADPH oxidase (Nox) family enzymes are one of the main sources of cellular reactive oxygen species (ROS), which have been shown to function as second messenger molecules. To date, seven members of this family have been reported, including Nox1-5 and Duox1 and -2. With the exception of Nox2, the regulation of the Nox enzymes is still poorly understood. Nox1 is highly expressed in the colon, and it requires two cytosolic regulators, NoxO1 and NoxA1, as well as the binding of Rac1 GTPase, for its activity. In this study, we investigate the role of the tyrosine kinase c-Src in the regulation of ROS formation by Nox1. We show that c-Src induces Nox1-mediated ROS generation in the HT29 human colon carcinoma cell line through a Rac-dependent mechanism. Treatment of HT29 cells with the Src inhibitor PP2, expression of a kinase-inactive form of c-Src, and c-Src depletion by small interfering RNA (siRNA) reduce both ROS generation and the levels of active Rac1. This is associated with decreased Src-mediated phosphorylation and activation of the Rac1-guanine nucleotide exchange factor Vav2. Consistent with this, Vav2 siRNA that specifically reduces endogenous Vav2 protein is able to dramatically decrease Nox1-dependent ROS generation and abolish c-Src-induced Nox1 activity. Together, these results establish c-Src as an important regulator of Nox1 activity, and they may provide insight into the mechanisms of tumor formation in colon cancers.

The Requirement of Reactive Oxygen Species Generation in the Apoptosis of Leukemia Cells Induced by 2-Methoxyestradiol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4370-4370
Author(s):  
Guo Kunyuan ◽  
Miaorong She ◽  
Haiyan Hu ◽  
Xinqing Niu ◽  
Sanfang Tu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Leukemia Cell ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract 2-Methoxyestradiol (2-ME) is a new anticancer agent currently under investigation for treatment of leukemia. We evaluated the effects of 2-ME-induced apoptosis in two myeloid leukemia cell lines (U937 and HL-60) in association with reactive oxygen species (ROS) generation. We found that 2-ME resulted in viability decrease in a dose-dependent manner, generated ROS: nitric oxide and superoxide anions, and mitochondria damage. 2-ME-induced apoptosis correlated with increase in ROS. Quenching of ROS with N-acetyl-L-cysteine protected leukemia cells from the cytotoxicity of 2-ME and prevented apoptosis induction by 2-ME. Furthermore, addition of manumycin, a farnesyltransferase inhibitor, demonstrated by our previous studies that induced apoptosis of leukemic cells and induced ROS, significantly enhanced the apoptosis-induced by 2-ME. In conclusion, cellular ROS generation play an important role in the cytotoxic effect of 2-ME. It is possible to use ROS-generation agents such as manumycin to enhance the antileukemic effect. Such a combination strategy need the further in vivo justify and may have potential clinical application.

The Combined Effects of Endotoxin and PM2.5 on Cytotoxicity and Reactive Oxygen Species Generation in A549 Cells

2012 ◽  
Vol 610-613 ◽  
pp. 794-797
Author(s):  
Yu Shang ◽  
Lan Lan Fan ◽  
Ling Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Cultured Cells ◽  
Inflammatory Responses ◽  
Reactive Oxygen Species Generation ◽  
A549 Cells ◽  
Reactive Oxygen ◽  
Epithelial Cell Line ◽  
Ros Generation ◽  
Combined Effects ◽  
Oxygen Species

Exposure to ambient particulate matter (PM) is found to be associated with adverse cardiopulmonary diseases. Endotoxin presented in PM is suggested to be one of the most important factors in triggering pro-inflammatory cytokine/chemokine release upon the exposure of PM. Pre-treated with endotoxin is found to enhance the inflammatory responses induced by PM in cultured cells. The aim of present study is to investigate the roles of endotoxin on the cytotoxicity and the generation of reactive oxygen species (ROS) induced by PM2.5 in a human lung epithelial cell line A549. The results find that PM2.5 induced a dose-dependent decrease in cell viability and pre-treated with endotoxin did not change the cytotoxicity of PM2.5 in A549 cells. Nevertheless the endotoxin significantly reduced the ROS generation in A549 induced by PM2.5 at the dose of 400 μg/mL. The results indicated that the combined effects of endotoxin and PM were complex and deserved further investigations.

scholarly journals Binary organic nanoparticles with enhanced reactive oxygen species generation capability for photodynamic therapy

2021 ◽  
pp. 2150009
Author(s):  
Xiaofu Weng ◽  
Zhouzhou Bao ◽  
Xunbin Wei
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Tumor Targeting ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Enhanced Fluorescence ◽  
New Strategy ◽  
Biological Environment

Photodynamic therapy (PDT) takes advantage of photosensitizers (PSs) to generate reactive oxygen species (ROS) for cell killing when excited by light. It has been widely used in clinic for therapy of multiple cancers. Currently, all the FDA-approved PSs, including porphyrin, are all small organic molecules, suffering from aggregation-caused quenching (ACQ) issues in biological environment and lacking tumor targeting capability. Nanoparticles (NPs) with size between 20[Formula: see text]nm and 200[Formula: see text]nm possess tumor targeting capability due to the enhanced permeability and retention (EPR) effect. It is urgent to develop a new strategy to form clinical-approved-PSs-based NPs with improved ROS generation capability. In this study, we report a strategy to overwhelm the ACQ of porphyrin by doping it with a type of aggregation-induced emission (AIE) luminogen to produce a binary NPs with high biocompatibility, and enhanced fluorescence and ROS generation capability. Such NPs can be readily synthesized by mixing a porphyrin derivative, Ce6 with a typical AIE luminogen, TPE-Br. Here, our experimental results have demonstrated the feasibility and effectiveness of this strategy, endowing it a great potential in clinical applications.

Abstract 91: Inhibition of Toll-like Receptor 4 Suppresses Reactive Oxygen Species Generation in Diabetic Vasculature

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Maria Alicia Carrillo-Sepulveda ◽  
Camilla Wenceslau ◽  
R. Clinton Webb
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Dysfunction ◽  
Reactive Oxygen Species Generation ◽  
Vascular Complications ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Tlr4 Signaling

Reactive oxygen species (ROS) are augmented in diabetes and play a central role in vascular dysfunction. TLR4, a key component of the innate immune system, is elevated during diabetes; however, the mechanistic link between TLR4, ROS, and vascular dysfunction remains elusive. Our previous results show that under high glucose (HG), TLR4 is upregulated in vascular smooth muscle cells (VSMCs) and mediates HG-induced ROS production. We hypothesized that TLR4 augments ROS in diabetic resistance vessels, which contributes to vascular dysfunction. To test our hypothesis, streptozotocin (STZ)-induced diabetic Sprague-Dawley rats (65mg/kg; 5weeks) were treated with 50ug/day of CLI-095, an inhibitor of TLR4, over 14 days. Glucose levels were increased (390±13 vs. 97±8.2mg/dL control) and body weight decreased (310±38.4 vs. 385±21g control) in the STZ group. These effects were unchanged by CLI-095 treatment. Mesenteric resistance arteries (MRA) from STZ rats exhibited impaired acetylcholine-induced relaxation (35.26±4.38% vs. 81.83±2.61% control, p<0.05), and CLI-095 treatment ameliorated this effect (71.99±3.48%, p<0.05). Moreover, dihydroethidium staining showed that the increase in ROS due to STZ (1.8 fold vs. control, p<0.05) was attenuated after CLI-095 treatment (1.6 fold vs. STZ, p<0.05). To test if TLR4 signaling is activated in MRA from the STZ rats, MyD88 protein levels, a downstream adaptor molecule, were measured. Arteries from the STZ rats showed increased expression of MyD88 (1.6 fold vs. control, p<0.05) which was reduced after CLI-095 treatment (1.2 fold vs. STZ, p<0.05). Finally, we assessed if TLR4 signaling in VSMCs following HG treatment is altered. Immunoprecipitation showed that HG did not alter the interaction between TLR4 and MyD88 in endothelial cells. In contrast, HG conditions increased TLR4 and MyD88 interaction in VSMCs. Concurrently, HG-induced activation of NFKB in VSMCs was diminished in cells pre-treated with CLI-095. Together our data suggest that activation of TLR4 signaling in VSMCs leads to ROS generation thereby contributing to a reduction in nitric oxide bioavailabitity contributing to endothelial dysfunction in diabetes. Thus, TLR4 is a putative target for the treatment of diabetic vascular complications.

scholarly journals Acrylamide Induces Mitophagy and Alters Macrophage Phenotype via Reactive Oxygen Species Generation

2021 ◽  
Vol 22 (4) ◽  
pp. 1683
Author(s):  
Chih-Hsing Hung ◽  
Yi-Ching Lin ◽  
Yi-Giien Tsai ◽  
Yu-Chih Lin ◽  
Chia-Hong Kuo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Confocal Laser ◽  
Ros Generation ◽  
Oxygen Species ◽  
Macrophage Phenotype ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Mitochondrial Respiratory Chain Complex

Acrylamide is a readily exposed toxic organic compound due to its formation in many carbohydrate rich foods that are cooked at high temperatures. Excessive production of reactive oxygen species (ROS), which is an important factor for mitophagy, has been reported to lead to airway inflammation, hyper-responsiveness, and remodeling. Epigenetic regulation is an important modification affecting gene transcription. In this study, the effects of acrylamide on ROS productions and mitophagy were investigated. The human monocytic cell line THP-1 was treated with acrylamide, and ROS productions were investigated by flow cytometry. The mitochondrial and epigenetic involvement was evaluated by quantitative real-time PCR. Histone modifications were examined by chromatin immunoprecipitation assays. Mitophagy was detected by Western blotting and confocal laser microscopy. Acrylamide promoted mitochondria-specific ROS generation in macrophages. The gene expression of mitochondrial respiratory chain complex II SDHA was increased under acrylamide treatment. Acrylamide induced histone H3K4 and H3K36 tri-methylation in an SDHA promoter and increased mitophagy-related PINK1 expression, which promoted a M2-like phenotypic switch with increase TGF-β and CCL2 levels in THP-1 cells. In conclusion, acrylamide induced ROS production through histone tri-methylation in an SDHA promoter and further increased the expression of mitophagy-related PINK-1, which was associated with a macrophage M2 polarization shift.

Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation

2002 ◽  
Vol 283 (5) ◽  
pp. H2054-H2061 ◽  
Author(s):  
Manabu Takano ◽  
Avedis Meneshian ◽  
Emran Sheikh ◽  
Yasuhiko Yamakawa ◽  
Kirsten Bass Wilkins ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Xanthine Oxidase ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Tnf Α ◽  
Early Peak ◽  
New Protein

Endothelial cell ICAM-1 upregulation in response to TNF-α is mediated in part by reactive oxygen species (ROS) generated by the endothelial membrane-associated NADPH oxidase and occurs maximally after 4 h as the synthesis of new protein is required. However, thrombin-stimulated P-selectin upregulation is bimodal, the first peak occurring within minutes. We hypothesize that this early peak, which results from the release of preformed P-selectin from within Weibel-Palade bodies, is mediated in part by ROS generated from the endothelial membrane-associated xanthine oxidase. We found that this rapid expression of P-selectin on the surface of endothelial cells was accompanied by qualitatively parallel increases in ROS generation. Both P-selectin expression and ROS generation were inhibited, dose dependently, by the exogenous administration of disparate cell-permeable antioxidants and also by the inhibition of either of the known membrane-associated ROS-generating enzymes NADPH oxidase or xanthine oxidase. This rapid, posttranslational cell signaling response, mediated by ROS generated not only by the classical NADPH oxidase but also by xanthine oxidase, may well represent an important physiological trigger of the microvascular inflammatory response.

scholarly journals Mitochondrial Ubiquitin Ligase MITOL Ubiquitinates Mutant SOD1 and Attenuates Mutant SOD1-induced Reactive Oxygen Species Generation

2009 ◽  
Vol 20 (21) ◽  
pp. 4524-4530 ◽  
Author(s):  
Ryo Yonashiro ◽  
Ayumu Sugiura ◽  
Misako Miyachi ◽  
Toshifumi Fukuda ◽  
Nobuko Matsushita ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Ubiquitin Ligase ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Misfolded Proteins ◽  
Mitochondrial Outer Membrane ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mutant Sod1

We have previously identified a novel mitochondrial ubiquitin ligase, MITOL, which is localized in the mitochondrial outer membrane and is involved in the control of mitochondrial dynamics. In this study, we examined whether MITOL eliminates misfolded proteins localized to mitochondria. Mutant superoxide dismutase1 (mSOD1), one of misfolded proteins, has been shown to localize in mitochondria and induce mitochondrial dysfunction, possibly involving in the onset and progression of amyotrophic lateral sclerosis. We found that in the mitochondria, MITOL interacted with and ubiquitinated mSOD1 but not wild-type SOD1. In vitro ubiquitination assay revealed that MITOL directly ubiquitinates mSOD1. Cycloheximide-chase assay in the Neuro2a cells indicated that MITOL overexpression promoted mSOD1 degradation and suppressed both the mitochondrial accumulation of mSOD1 and mSOD1-induced reactive oxygen species (ROS) generation. Conversely, the overexpression of MITOL CS mutant and MITOL knockdown by specific siRNAs resulted in increased accumulation of mSOD1 in mitochondria, which enhanced mSOD1-induced ROS generation and cell death. Thus, our findings indicate that MITOL plays a protective role against mitochondrial dysfunction caused by the mitochondrial accumulation of mSOD1 via the ubiquitin–proteasome pathway.

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