scholarly journals NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiao Xue ◽  
Chenxiao Yu ◽  
Yiting Tang ◽  
Wei Mo ◽  
Zhicheng Tang ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Expression Profiles ◽  
Antioxidant Response ◽  
High Dose ◽  
Related Factor ◽  
Skin Injury ◽  
Skin Cells ◽  
Dose Irradiation ◽  
Radiation Induced

Radiation-induced skin injury (RISI) commonly occur in cancer patients who received radiotherapy and is one of the first clinical symptoms after suffering from nuclear exposure. Oxidative damage is the major causes of RISI. Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a key mediator of the cellular antioxidant response. However, whether Nrf2 can alleviate RISI after high-dose irradiation remains unknown. In this study, we demonstrated that Nrf2-deficient (Nrf2-/-) mice were susceptible to high-dose irradiation and adenovirus-mediated overexpression of Nrf2 (ad-Nrf2) protected against radiation in skin cells. Overexpression of Nrf2 attenuated the severity of skin injury after high-dose electron beam irradiation. To uncover the mechanisms of Nrf2 involved in RISI, mRNA sequencing technology was performed to analyze the mRNA expression profiles of Ad-Nrf2 skin cells following radiation. The results revealed that a total of 127 genes were significantly changed, 55 genes were upregulated, and 72 genes were downregulated after Nrf2 overexpression. GSEA showed that Nrf2 was associated with positive regulation of genes involved in the reactive oxygen species pathway after radiation. Taken together, this study illustrated the role of Nrf2 in RISI and provided potentially strategies for ameliorating RISI.

scholarly journals Marine Compound 3-bromo-4,5-dihydroxybenzaldehyde Protects Skin Cells against Oxidative Damage via the Nrf2/HO-1 Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 234 ◽  
Author(s):  
Yea Seong Ryu ◽  
Pincha Devage Sameera Madushan Fernando ◽  
Kyoung Ah Kang ◽  
Mei Jing Piao ◽  
Ao Xuan Zhen ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Antioxidant Response ◽  
Signaling Cascades ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Skin Cells ◽  
Reverse Transcription Pcr ◽  
Extracellular Signal ◽  
Diphenyltetrazolium Bromide ◽  
Marine Compound

In this study, we aimed to illustrate the potential bio-effects of 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on the antioxidant/cytoprotective enzyme heme oxygenase-1 (HO-1) in keratinocytes. The antioxidant effects of 3-BDB were examined via reverse transcription PCR, Western blotting, HO-1 activity assay, and immunocytochemistry. Chromatin immunoprecipitation analysis was performed to test for nuclear factor erythroid 2-related factor 2 (Nrf2) binding to the antioxidant response element of the HO-1 promoter. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the cytoprotective effects of 3-BDB were mediated by the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, Akt) signaling. Moreover, 3-BDB induced the phosphorylation of ERK and Akt, while inhibitors of ERK and Akt abrogated the 3-BDB-enhanced levels of HO-1 and Nrf2. Finally, 3-BDB protected cells from H2O2- and UVB-induced oxidative damage. This 3-BDB-mediated cytoprotection was suppressed by inhibitors of HO-1, ERK, and Akt. The present results indicate that 3-BDB activated Nrf2 signaling cascades in keratinocytes, which was mediated by ERK and Akt, upregulated HO-1, and induced cytoprotective effects against oxidative stress.

scholarly journals Dose dependence of efficacy but not of safety in sublingual immunotherapy

2016 ◽  
Vol 65 (1) ◽  
Author(s):  
F. Frati ◽  
C. Incorvaia ◽  
F. Marcucci ◽  
L. Sensi ◽  
G. Di Cara ◽  
...  
Keyword(s):  
Sublingual Immunotherapy ◽  
Clinical Symptoms ◽  
Meta Analysis ◽  
Dose Dependence ◽  
Subcutaneous Immunotherapy ◽  
High Dose ◽  
Systemic Reactions ◽  
Significant Difference

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies.

scholarly journals A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junko Okano ◽  
Yuki Nakae ◽  
Takahiko Nakagawa ◽  
Miwako Katagi ◽  
Tomoya Terashima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Underlying Mechanism ◽  
Basal Cells ◽  
Barrier Dysfunction ◽  
Skin Injury ◽  
Accelerated Proliferation ◽  
Radiation Induced ◽  
Bone Marrow Derived Cells ◽  
Injury Recovery

AbstractExposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

scholarly journals Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

2015 ◽  
Vol 89 (21) ◽  
pp. 10959-10969 ◽  
Author(s):  
Donata Hoffmann ◽  
Annika Franke ◽  
Maria Jenckel ◽  
Aistė Tamošiūnaitė ◽  
Julia Schluckebier ◽  
...  
Keyword(s):  
Respiratory Symptoms ◽  
Clinical Symptoms ◽  
Common Vole ◽  
Reservoir Host ◽  
High Dose ◽  
Cowpox Virus ◽  
Common Voles ◽  
Highly Virulent

ABSTRACTThe incidence of human cowpox virus (CPXV) infections has increased significantly in recent years. Serological surveys have suggested wild rodents as the main CPXV reservoir. We characterized a CPXV isolated during a large-scale screening from a feral common vole. A comparison of the full-length DNA sequence of this CPXV strain with a highly virulent pet rat CPXV isolate showed a sequence identity of 96%, including a large additional open reading frame (ORF) of about 6,000 nucleotides which is absent in the reference CPXV strain Brighton Red. Electron microscopy analysis demonstrated that the vole isolate, in contrast to the rat strain, forms A-type inclusion (ATI) bodies with incorporated virions, consistent with the presence of completeatiandp4cgenes. Experimental infections showed that the vole CPXV strain caused only mild clinical symptoms in its natural host, while all rats developed severe respiratory symptoms followed by a systemic rash. In contrast, common voles infected with a high dose of the rat CPXV showed severe signs of respiratory disease but no skin lesions, whereas infection with a low dose led to virus excretion with only mild clinical signs. We concluded that the common vole is susceptible to infection with different CPXV strains. The spectrum ranges from well-adapted viruses causing limited clinical symptoms to highly virulent strains causing severe respiratory symptoms. In addition, the low pathogenicity of the vole isolate in its eponymous host suggests a role of common voles as a major CPXV reservoir, and future research will focus on the correlation between viral genotype and phenotype/pathotype in accidental and reservoir species.IMPORTANCEWe report on the first detection and isolation of CPXV from a putative reservoir host, which enables comparative analyses to understand the infection cycle of these zoonotic orthopox viruses and the relevant genes involved.In vitrostudies, including whole-genome sequencing as well asin vivoexperiments using the Wistar rat model and the vole reservoir host allowed us to establish links between genomic sequences and thein vivoproperties (virulence) of the novel vole isolate in comparison to those of a recent zoonotic CPXV isolated from pet rats in 2009. Furthermore, the role of genes present only in a reservoir isolate can now be further analyzed. These studies therefore allow unique insights and conclusions about the role of the rodent reservoir in CPXV epidemiology and transmission and about the zoonotic threat that these viruses represent.

Luminescence and radiation-induced color centers in anion-defective alumina crystals after high-dose irradiation

2016 ◽  
Vol 90 ◽  
pp. 90-93 ◽  
Author(s):  
V.S. Kortov ◽  
V.A. Pustovarov ◽  
S.V. Zvonarev ◽  
T.V. Shtang
Keyword(s):  
Color Centers ◽  
High Dose ◽  
Dose Irradiation ◽  
Radiation Induced

scholarly journals The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury

2017 ◽  
Vol 312 (2) ◽  
pp. L155-L162 ◽  
Author(s):  
Hailin Zhao ◽  
Shiori Eguchi ◽  
Azeem Alam ◽  
Daqing Ma
Keyword(s):  
Lung Injury ◽  
Therapeutic Potential ◽  
Antioxidant Response ◽  
Protective Role ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Nuclear Factor ◽  
Obstructive Pulmonary Disease ◽  
Antioxidant Response Elements

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents, and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2-antioxidant pathway has been shown to be important in the protection against various lung injuries including acute lung injury/acute respiratory distress syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and allergy and was widely examined for new therapeutic targets. The present review explores the protective role of Nrf-2 against lung injury and the therapeutic potential in targeting Nrf-2.

scholarly journals Role of high dose octreotide LAR for the treatment of GEP-NETs

2009 ◽  
Vol 3 (1) ◽  
pp. 7-14
Author(s):  
Giulia M. Franchi ◽  
Chiara Cappelletti ◽  
Valentina V. Villa ◽  
Emanuele Bosi ◽  
Marco F. Manzoni
Keyword(s):  
Quality Of Life ◽  
Tumour Growth ◽  
Neuroendocrine Tumours ◽  
Clinical Symptoms ◽  
Standard Dose ◽  
Diagnostic Tools ◽  
High Dose ◽  
Octreotide Lar

Neuroendocrine Tumours (NETs) are a heterogeneous group of rare neoplasms that account for 0,5% of all malignancies. The increased incidence observed in the last few decades may be accounted for by increased awareness, improved diagnostic tools and a revision in the definition. The main primary sites are the gastro-entero-pancreatic (GEP) tract (62-67%), and the lung (22-27%). In patients with GEP-NETs, the strongest predictor of 5-years survival is the staging. An adequate clinical management of GEP-NETs should be multidisciplinary and should aim at assuring a good quality of life. Somatostatin (sst) analogues are widely used in these tumours, which often express sst receptors, since they are demonstrated to reduce clinical symptoms and tumour growth. Herein we explore the usefulness of doubling octreotide LAR dose in selected patients after escaping from symptoms control and/or tumour stabilization in course of treatment with standard dose.

scholarly journals Protective Role of Nuclear Factor-Erythroid 2-Related Factor 2 Against Radiation-Induced Lung Injury and Inflammation

2018 ◽  
Vol 8 ◽  
Author(s):  
Xiaoli Tian ◽  
Feng Wang ◽  
Yuan Luo ◽  
Shijing Ma ◽  
Nannan Zhang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Radiation Induced
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