scholarly journals Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nicola Alessio ◽  
Tiziana Squillaro ◽  
Giovanni Di Bernardo ◽  
Giovanni Galano ◽  
Roberto De Rosa ◽  
...  
Keyword(s):  
Low Dose ◽  
Human Subjects ◽  
Aging Effect ◽  
Genotoxic Stress ◽  
Paracrine Signaling ◽  
X Ray ◽  
Dose Irradiation ◽  
Secretory Phenotype ◽  
Stress Mediator

Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein.

scholarly journals ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 72
Author(s):  
Denise Eckert ◽  
Felicitas Rapp ◽  
Ayele T. Tsedeke ◽  
Jessica Molendowska ◽  
Robert Lehn ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Radiation Source ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Microvascular Endothelial Cells ◽  
X Ray ◽  
Dose Irradiation ◽  
Intracellular Ros ◽  
Static Conditions

Anti-inflammatory effects of low-dose irradiation often follow a non-linear dose–effect relationship. These characteristics were also described for the modulation of leukocyte adhesion to endothelial cells. Previous results further revealed a contribution of reactive oxygen species (ROS) and anti-oxidative factors to a reduced leukocyte adhesion. Here, we evaluated the expression of anti-oxidative enzymes and the transcription factor Nrf2 (Nuclear factor-erythroid-2-related factor 2), intracellular ROS content, and leukocyte adhesion in primary human microvascular endothelial cells (HMVEC) upon low-dose irradiation under physiological laminar shear stress or static conditions after irradiation with X-ray or Carbon (C)-ions (0–2 Gy). Laminar conditions contributed to increased mRNA expression of anti-oxidative factors and reduced ROS in HMVEC following a 0.1 Gy X-ray and 0.5 Gy C-ion exposure, corresponding to reduced leukocyte adhesion and expression of adhesion molecules. By contrast, mRNA expression of anti-oxidative markers and adhesion molecules, ROS, and leukocyte adhesion were not altered by irradiation under static conditions. In conclusion, irradiation of endothelial cells with low doses under physiological laminar conditions modulates the mRNA expression of key factors of the anti-oxidative system, the intracellular ROS contents of which contribute at least in part to leucocyte adhesion, dependent on the radiation source.

The Effect of Low-Dose Irradiation on Proliferation of Mammalian Cells In Vitro

1996 ◽  
Vol 146 (3) ◽  
pp. 329 ◽  
Author(s):  
Yu. N. Korystov ◽  
N. A. Eliseeva ◽  
L. N. Kublik ◽  
A. A. Narimanov
Keyword(s):  
Mammalian Cells ◽  
Low Dose ◽  
Dose Irradiation

scholarly journals Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249683
Author(s):  
Md Abdur Rashid ◽  
Saiqa Muneer ◽  
Tony Wang ◽  
Yahya Alhamhoom ◽  
Llew Rintoul ◽  
...  
Keyword(s):  
Low Dose ◽  
Structural Integrity ◽  
Dry Powder Inhaler ◽  
Pulmonary Delivery ◽  
Magnesium Stearate ◽  
Hplc Method ◽  
Dry Powder ◽  
Scanning Calorimetry ◽  
X Ray

This study aims at developing and characterizing the puerarin dry powder inhaler (DPI) formulations for pulmonary delivery. The inhalable particles size (<2 μm) was accomplished by micronization and its morphology was examined by scanning electron microscopy (SEM). The puerarin-excipient interaction in powder mixtures was analyzed by using Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder Diffraction (XRD), and differential scanning calorimetry (DSC) methods. Using a Twin stage impinger (TSI), the in-vitro aerosolization of the powder formulations was carried out at a flow rate of 60 L/min and the drug was quantified by employing a validated HPLC method. No significant interactions between the drug and the excipients were observed in the powder formulations. The fine particle fraction (FPF) of the drug alone was 4.2% which has increased five to six-fold for the formulations with aerosolization enhancers. Formulation containing lactose as large carriers produced 32.7% FPF, which further increased with the addition of dispersibility enhancers, leucine and magnesium stearate (40.8% and 41.2%, respectively). The Raman and FTIR techniques are very useful tool for understanding structural integrity and stability of the puerarin in the powder formulations. The puerarin was found to be compatible with the excipients used and the developed DPI formulation may be considered as an efficient formulation for pulmonary delivery for the management of various diseases at a very low dose.

scholarly journals Changes in the content of carotenoids and flavonoids in medicinal raw material of Digitalis purpurea, Polemonium caeruleum, and Aerva lanata, cultivated in vitro under the chronic action of ionizing radiation

2021 ◽  
Vol 22 (1) ◽  
pp. 85-92
Author(s):  
S.V. Litvinov ◽  
◽  
L.G. Lioshyna ◽  
O.V. Bulko ◽  
K.V. Lystvan ◽  
...  
Keyword(s):  
Low Dose ◽  
Raw Material ◽  
Small Range ◽  
Γ Irradiation ◽  
Digitalis Purpurea ◽  
Dose Irradiation ◽  
Post Radiation ◽  
Aerva Lanata ◽  
The Individual

Chronic low-dose γ-irradiation of Digitalis purpurea and Aerva lanata plants in vitro have led to an increase in the content of carotenoids and flavonoids in the leaves at the beginning of the post-radiation period. In the following, the content of pigments and flavonoids decreased in comparison to the control samples. For Polemonium caeruleum such changes had been not observed. The qualitative composition of the secondary metabolites has not been changed, but the ratio of the individual components of the extract varied within a small range. Ri-transformants of Digitalis purpurea have been shown smaller changes in response to irradiation. We assume that the observed effects are the manifestation of the adaptive response of plants to oxidative stress caused by chronic low-dose irradiation.

scholarly journals Aged-senescent cells contribute to impaired heart regeneration

2018 ◽  
Author(s):  
Fiona C. Lewis-McDougall ◽  
Prashant J. Ruchaya ◽  
Eva Domenjo-Vila ◽  
Tze Shin Teoh ◽  
Larissa Prata ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Human Subjects ◽  
Heart Regeneration ◽  
Therapeutic Approaches ◽  
Infarcted Heart ◽  
Extensive Analysis ◽  
Secretory Phenotype ◽  
Aged Subjects

AbstractAging leads to increased cellular senescence and is associated with decreased potency of tissue-specific stem/progenitor cells. Here we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease (n=119), aged 32-86 years. In aged subjects (>74 years old) over half of CPCs are senescent (p16INK4A, SA-β-gal, DNA damage γH2AX, telomere length, Senescence-Associated Secretory Phenotype (SASP)), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK-ATTAC or wildtype mice treated with D+Q senolytics) in vivo activates resident CPCs (0.23±0.06% vs. 0.01±0.01% vehicle; p<0.05) and increased the number of small, proliferating Ki67-, EdU-positive cardiomyocytes (0.25±0.07% vs. 0.03±0.03% vehicle; p<0.05). Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and rejuvenate the regenerative capacity of the heart.

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