nuclear fragmentation
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Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5579
Author(s):  
Laura Martínez-Escardó ◽  
Montse Alemany ◽  
María Sánchez-Osuna ◽  
Alejandro Sánchez-Chardi ◽  
Meritxell Roig-Martínez ◽  
...  

Glioblastoma (GBM) is a highly aggressive brain tumor and almost all patients die because of relapses. GBM-derived cells undergo cell death without nuclear fragmentation upon treatment with different apoptotic agents. Nuclear dismantling determines the point-of-no-return in the apoptotic process. DFF40/CAD is the main endonuclease implicated in apoptotic nuclear disassembly. To be properly activated, DFF40/CAD should reside in the cytosol. However, the endonuclease is poorly expressed in the cytosol and remains cumulated in the nucleus of GBM cells. Here, by employing commercial and non-commercial patient-derived GBM cells, we demonstrate that the natural terpenoid aldehyde gossypol prompts DFF40/CAD-dependent nuclear fragmentation. A comparative analysis between gossypol- and staurosporine-treated cells evidenced that levels of neither caspase activation nor DNA damage were correlated with the ability of each compound to induce nuclear fragmentation. Deconvoluted confocal images revealed that DFF40/CAD was almost completely excluded from the nucleus early after the staurosporine challenge. However, gossypol-treated cells maintained DFF40/CAD in the nucleus for longer times, shaping a ribbon-like structure piercing the nuclear fragments and building a network of bridged masses of compacted chromatin. Therefore, GBM cells can fragment their nuclei if treated with the adequate insult, making the cell death process irreversible.


Symmetry ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1887
Author(s):  
Theodoros Gaitanos

In this article we review the important role of non-equilibrium dynamics in reactions induced by ions and hadron beams to understand the fragmentation processes inside hadronic media. We discuss the single-particle dynamics in specific sources such as spectators in heavy-ion collisions and residual nuclear targets in hadron-induced reactions. Particular attention is given to the dynamics of hyperons. We further discuss the question regarding the onset of local instabilities, which are relevant for the appearance of fragmentation phenomena in nuclear reactions. We apply the theoretical formalism, that is, semi-classical transport embedded with statistical methods of nuclear fragmentation, to reactions induced by light ions and hadron beams. We discuss the results of nuclear fragmentation and, in particular, examine the formation of hypernuclei. Such studies are important for obtaining a deeper understanding of the equation of state in fragmenting matter and are relevant for forthcoming experiments, such as PANDA at FAIR and J-PARC in Japan.


2021 ◽  
Author(s):  
Ziqiang Zhang ◽  
Yingying Sun ◽  
Haojie Wang ◽  
Yuxiang Yang ◽  
Ruiqi Dong ◽  
...  

Abstract Background and PurposeIn this study, the therapeutic effect of Mel-incubated ADSCs on CCl4-induced hepatic fibrosis was investigated. MethodsThe experiment was arranged into ADSCS group, ADSCS + Mel group, Model group and Control group with 10 mice in each group. The other three groups of mice were intraperitoneally injected with 8% CCl4, and the control group was injected with the same dose of PBS twice a week for 4 weeks. From the fifth week, ADSCs group and ADSCs + Mel group mice were injected with 1×106 cells/1 ml PBS dose of ADSCs and 50 μM Mel pretreated ADSCs into tail vein, respectively, twice a week for 2 weeks, and mice in the control and model groups were injected with the same dose of PBS. Samples were tested after six weeks. ResultsIn model group, severe histomathological changes were observed in liver, including severe vacuolation, nuclear fragmentation and liver fibrosis, and these changes were ameliorated by Mel pretreated ADSCs. At the same time, RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of pro-apoptotic genes (Caspase-8, Bax and Caspase-3), and promoted the expression of anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9, TGF-β, MMP-2 yellow-stained positive cells were found in the liver tissues of the model group, while the expression of positive cells was blocked by Mel-induced ADSCs. Conclusion and ImplicationsADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis, which provides a reference for clinical treatment of liver injury with mesenchymal stem cells.


Author(s):  
Anissa Bey ◽  
Jiasen Ma ◽  
Keith M. Furutani ◽  
Michael G. Herman ◽  
Jedediah E. Johnson ◽  
...  

Abstract Purpose This article presents an in vivo imaging technique based on nuclear fragmentation of carbon ions in irradiated tissues for potential real-time monitoring of carbon-ion radiation therapy (CIRT) treatment delivery and quality assurance purposes in clinical settings. Materials and Methods A proof-of-concept imaging and monitoring system (IMS) was devised to implement the technique. Monte Carlo simulations were performed for a prospective pencil-beam scanning CIRT nozzle. The development IMS benchmark considered a 5×5-cm2 pixelated charged-particle detector stack positioned downstream from a target phantom and list-mode data acquisition. The abundance and production origins, that is, vertices, of the detected fragments were studied. Fragment trajectories were approximated by straight lines and a beam back-projection algorithm was built to reconstruct the vertices. The spatial distribution of the vertices was then used to determine plan relevant markers. Results The IMS technique was applied for a simulated CIRT case, a primary brain tumor. Four treatment plan monitoring markers were conclusively recovered: a depth dose distribution correlated profile, ion beam range, treatment target boundaries, and the beam spot position. Promising millimeter-scale (3-mm, ≤10% uncertainty) beam range and submillimeter (≤0.6-mm precision for shifts <3 cm) beam spot position verification accuracies were obtained for typical therapeutic energies between 150 and 290 MeV/u. Conclusions This work demonstrated a viable online monitoring technique for CIRT treatment delivery. The method's strong advantage is that it requires few signal inputs (position and timing), which can be simultaneously acquired with readily available technology. Future investigations will probe the technique's applicability to motion-sensitive organ sites and patient tissue heterogeneities. In-beam measurements with candidate detector-acquisition systems are ultimately essential to validate the IMS benchmark performance and subsequent deployment in the clinic.


2021 ◽  
Author(s):  
Anjalika Chongtham ◽  
J Mario Isas ◽  
Nitin K Pandey ◽  
Anoop Rawat ◽  
Jung Hyun Yoo ◽  
...  

HD is a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) repeats in the exon-1 of huntingtin protein (HTT). The expanded polyQ enhances the amyloidogenic propensity of HTT exon 1 (HTTex1), which forms a heterogeneous mixture of assemblies with some being neurotoxic. While predominantly intracellular, monomeric and aggregated mutant HTT species are also present in the cerebrospinal fluids of HD patients, however, their biological properties are not well understood. To explore the role of extracellular mutant HTT in aggregation and toxicity, we investigated the possible uptake and amplification of recombinant HTTex1 assemblies in cell culture models. We found seedingcompetent species in the sonicated HTTex1 fibrils, which preferentially entered human neurons and triggered the amplification of neurotoxic assemblies; astrocytes or epithelial cells were not permissive to the HTTex1 seeding. The aggregation of HTTex1 seeds in neurons depleted endogenous HTT protein with non-pathogenic polyQ repeat, activated apoptotic caspase-3 pathway and induced nuclear fragmentation. Using a panel of novel monoclonal antibodies and genetic mutation, we identified epitopes within the N-terminal 17 amino acids and proline-rich domain of HTTex1 mediating neural seeding. Synaptosome preparations from the brains of HD mice also contained similar neurotoxic seeding-competent mutant HTT species. Our findings suggest that amyloidogenic extracellular mutant HTT assemblies may selectively enter neurons, propagate and produce neurotoxic assemblies.


2021 ◽  
Vol 8 ◽  
Author(s):  
Giuseppe Battistoni ◽  
Marco Toppi ◽  
Vincenzo Patera ◽  
The FOOT Collaboration

In Charged Particle Therapy (PT) proton or 12C beams are used to treat deep-seated solid tumors exploiting the advantageous characteristics of charged particles energy deposition in matter. For such projectiles, the maximum of the dose is released at the end of the beam range, in the Bragg peak region, where the tumour is located. However, the nuclear interactions of the beam nuclei with the patient tissues can induce the fragmentation of projectiles and/or target nuclei and needs to be carefully taken into account when planning the treatment. In proton treatments, the target fragmentation produces low energy, short range fragments along all the beam path, that deposit a non-negligible dose especially in the first crossed tissues. On the other hand, in treatments performed using 12C, or other (4He or 16O) ions of interest, the main concern is related to the production of long range fragments that can release their dose in the healthy tissues beyond the Bragg peak. Understanding nuclear fragmentation processes is of interest also for radiation protection in human space flight applications, in view of deep space missions. In particular 4He and high-energy charged particles, mainly 12C, 16O, 28Si and 56Fe, provide the main source of absorbed dose in astronauts outside the atmosphere. The nuclear fragmentation properties of the materials used to build the spacecrafts need to be known with high accuracy in order to optimise the shielding against the space radiation. The study of the impact of these processes, which is of interest both for PT and space radioprotection applications, suffers at present from the limited experimental precision achieved on the relevant nuclear cross sections that compromise the reliability of the available computational models. The FOOT (FragmentatiOn Of Target) collaboration, composed of researchers from France, Germany, Italy and Japan, designed an experiment to study these nuclear processes and measure the corresponding fragmentation cross sections. In this work we discuss the physics motivations of FOOT, describing in detail the present detector design and the expected performances, coming from the optimization studies based on accurate FLUKA MC simulations and preliminary beam test results. The measurements planned will be also presented.


Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 85
Author(s):  
Iulia Pinzaru ◽  
Alina Tanase ◽  
Virgil Enatescu ◽  
Dorina Coricovac ◽  
Flavia Bociort ◽  
...  

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders.


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