scholarly journals Advanced Omics and Radiobiological Tissue Archives: The Future in the Past

2021 ◽  
Vol 11 (23) ◽  
pp. 11108
Author(s):  
Omid Azimzadeh ◽  
Maria Gomolka ◽  
Mandy Birschwilks ◽  
Shin Saigusa ◽  
Bernd Grosche ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Radiation Effects ◽  
Molecular Mechanisms ◽  
Clinical Performance ◽  
Biological Effects ◽  
Extraction Methods ◽  
Biological Information ◽  
Molecular Fingerprints ◽  
Ffpe Samples ◽  
Ffpe Tissues

Archival formalin-fixed, paraffin-embedded (FFPE) tissues and their related diagnostic records are an invaluable source of biological information. The archival samples can be used for retrospective investigation of molecular fingerprints and biomarkers of diseases and susceptibility. Radiobiological archives were set up not only following clinical performance such as cancer diagnosis and therapy but also after accidental and occupational radiation exposure events where autopsies or cancer biopsies were sampled. These biobanks provide unique and often irreplaceable materials for the understanding of molecular mechanisms underlying radiation-related biological effects. In recent years, the application of rapidly evolving “omics” platforms, including transcriptomics, genomics, proteomics, metabolomics and sequencing, to FFPE tissues has gained increasing interest as an alternative to fresh/frozen tissue. However, omics profiling of FFPE samples remains a challenge mainly due to the condition and duration of tissue fixation and storage, and the extraction methods of biomolecules. Although biobanking has a long history in radiation research, the application of omics to profile FFPE samples available in radiobiological archives is still young. Application of the advanced omics technologies on archival materials provides a new opportunity to understand and quantify the biological effects of radiation exposure. These newly generated omics data can be well integrated into results obtained from earlier experimental and epidemiological analyses to shape a powerful strategy for modelling and evaluating radiation effects on health outcomes. This review aims to give an overview of the unique properties of radiation biobanks and their potential impact on radiation biology studies. Studies recently performed on FFPE samples from radiobiology archives using advanced omics are summarized. Furthermore, the compatibility of archived FFPE tissues for omics analysis and the major challenges that lie ahead are discussed.

Strahlenwirkung am Normalgewebe

2010 ◽  
Vol 49 (S 01) ◽  
pp. S53-S58 ◽  
Author(s):  
W. Dörr
Keyword(s):  
Radiation Exposure ◽  
Normal Tissue ◽  
Radiation Effects ◽  
A Priori ◽  
Cell Loss ◽  
Turnover Time ◽  
Complete Healing ◽  
Internal Radiotherapy ◽  
Normal Tissues ◽  
Chronic Radiation

SummaryThe curative effectivity of external or internal radiotherapy necessitates exposure of normal tissues with significant radiation doses, and hence must be associated with an accepted rate of side effects. These complications can not a priori be considered as an indication of a too aggressive therapy. Based on the time of first diagnosis, early (acute) and late (chronic) radiation sequelae in normal tissues can be distinguished. Early reactions per definition occur within 90 days after onset of the radiation exposure. They are based on impairment of cell production in turnover tissues, which in face of ongoing cell loss results in hypoplasia and eventually a complete loss of functional cells. The latent time is largely independent of dose and is defined by tissue biology (turnover time). Usually, complete healing of early reactions is observed. Late radiation effects can occur after symptom-free latent times of months to many years, with an inverse dependence of latency on dose. Late normal tissue changes are progressive and usually irreversible. They are based on a complex interaction of damage to various cell populations (organ parenchyma, connective tissue, capillaries), with a contribution from macrophages. Late effects are sensitive for a reduction in dose rate (recovery effects).A number of biologically based strategies for protection of normal tissues or for amelioration of radiation effects was and still is tested in experimental systems, yet, only a small fraction of these approaches has so far been introduced into clinical studies. One advantage of most of the methods is that they may be effective even if the treatment starts way after the end of radiation exposure. For a clinical exploitation, hence, the availability of early indicators for the progression of subclinical damage in the individual patient would be desirable. Moreover, there is need to further investigate the molecular pathogenesis of normal tissue effects in more detail, in order to optimise biology based preventive strategies, as well as to identify the precise mechanisms of already tested approaches (e. g. stem cells).

scholarly journals Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1676
Author(s):  
Giulia Rossi ◽  
Martina Placidi ◽  
Chiara Castellini ◽  
Francesco Rea ◽  
Settimio D'Andrea ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Cellular Damage ◽  
X Rays ◽  
Adolescent Cancer ◽  
Radiation Induced ◽  
Vitro Model ◽  
Underlying Mechanisms

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

Acidic Aqueous Extraction of Hypothalamic Luteinizing Hormone Releasing Hormone to Study Biological Effects

1974 ◽  
Vol 52 (3) ◽  
pp. 754-758 ◽  
Author(s):  
S. H. Shin ◽  
C. J. Howitt
Keyword(s):  
Luteinizing Hormone ◽  
Biological Effects ◽  
Extraction Procedure ◽  
Extraction Methods ◽  
Water Soluble ◽  
Acid Extraction ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Aqueous Solvent ◽  
Lh Rh

Several aqueous solvent systems were tested for their efficiency in extracting luteinizing hormone releasing hormone (LH-RH) from rat hypothalamus. Although LH-RH is a water-soluble decapeptide, neutral distilled water extracted only 10% of the LH-RH obtained using acid extraction methods. The efficiency of the acid extraction procedure suggests that in the hypothalamus the releasing hormone is bound to a relatively large molecular weight compound. Using the acidic extraction procedure, we found that hypothalamic LH-RH content is significantly lower in the castrated animal than in the normal rat.

scholarly journals SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3203
Author(s):  
Margherita Sisto ◽  
Domenico Ribatti ◽  
Sabrina Lisi
Keyword(s):  
Sjögren’S Syndrome ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Sjögren's Syndrome ◽  
Biological Effects ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Mesenchymal Transition ◽  
Sjögren‘S Syndrome

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-β family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

Microglia extracellular vesicles: focus on molecular composition and biological function

2021 ◽  
Vol 49 (4) ◽  
pp. 1779-1790 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Chiara Giacomelli ◽  
Laura Marchetti ◽  
Claudia Martini
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Biological Effects ◽  
Genetic Material ◽  
Cell Communication ◽  
Molecular Composition ◽  
Cargo Proteins ◽  
A Cell ◽  
The Central Nervous System

Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.

scholarly journals Hypothyroidism after radiation exposure: brief narrative review

2020 ◽  
Vol 127 (11) ◽  
pp. 1455-1466
Author(s):  
Christoph Reiners ◽  
Valentina Drozd ◽  
Shunichi Yamashita
Keyword(s):  
Radiation Therapy ◽  
Radiation Exposure ◽  
Molecular Mechanisms ◽  
External Beam Radiotherapy ◽  
Thyroid Autoimmunity ◽  
External Irradiation ◽  
Reactor Accident ◽  
Dose Threshold ◽  
Iodine 131 ◽  
Risk Of Cancer

Abstract The thyroid gland is among the organs at the greatest risk of cancer from ionizing radiation. Epidemiological evidence from survivors of radiation therapy, atomic bombing, and the Chernobyl reactor accident, clearly shows that radiation exposure in childhood can cause thyroid cancer and benign thyroid nodules. Radiation exposure also may induce hypothyroidism and autoimmune reactions against the thyroid, but these effects are less well-documented. The literature includes only a few, methodologically weak animal studies regarding genetic/molecular mechanisms underlying hypothyroidism and thyroid autoimmunity after radiation exposure. Rather, evidence about radiation-induced hypothyroidism and thyroid autoimmunity derives mainly from follow-up studies in patients treated with external beam radiotherapy (EBRT) or iodine-131, and from epidemiological studies in the atomic bombing or nuclear accident survivors. Historically, hypothyroidism after external irradiation of the thyroid in adulthood was considered not to develop below a 10–20 Gy dose threshold. Newer data suggest a 10 Gy threshold after EBRT. By contrast, data from patients after iodine-131 “internal radiation therapy” of Graves´ disease indicate that hypothyroidism rarely occurs below thyroid doses of 50 Gy. Studies in children affected by the Chernobyl accident indicate that the dose threshold for hypothyroidism may be considerably lower, 3–5 Gy, aligning with observations in A-bomb survivors exposed as children. The reasons for these dose differences in radiosensitivity are not fully understood. Other important questions about the development of hypothyroidism after radiation exposure e.g., in utero, about the interaction between autoimmunity and hypofunction, and about the different effects of internal and external irradiation still must be answered.

scholarly journals The Effect of 5-hydroxytryptamine on Smooth Muscles is Impacted by Broadband UV and LED UV and Blue Light

2021 ◽  
Vol 25 (4) ◽  
pp. 331-342
Author(s):  
Charilaos Xenodochidis ◽  
◽  
Milena Draganova-Filipova ◽  
George Miloshev ◽  
Milena Georgieva ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Smooth Muscles ◽  
Light Sources ◽  
Organ Bath ◽  
Light Emitting ◽  
Signaling Systems ◽  
Positive Effects ◽  
Lamp Source

Due to their effects, similar to low-intensity therapy light sources such as light-emitting diodes (LED) and broadband spectrum lamps have recently become commonly used in the diagnosis and treatment of neurodegenerative pathologies, cancer, as well as ageing. Despite the proven positive effects of such therapies, deeper understanding of the light therapies’ biological effects remains unclear. Even more, the molecular mechanisms through which different neurotransmitters, namely serotonin (5-hydroxytryptamine, 5-HT), mediate the organism’s response to radiation are yet indistinct. In this paper, we present the design and development of a specialized system for irradiation of biological objects, which is composed of LED 365 nm and LED 470 nm and a broadband lamp source of UVA/B (350 nm) with intensity, power density and direction, which can be optimized experimentally. The system, named a “water organ bath (wob)”, is used in the current work to irradiate smooth muscle stomach strips of rats. The obtained results prove that the modulation of the spontaneous contractile smooth muscle activity and the potentiation of the effects of major neurotransmitters are executed by the emitted light. The probable explanation for the neurotransmitters photoactivation is that it is the resultant effect of electromagnetic radiation on intracellular enzymes signaling systems.

The LPA-CDK5-Tau Pathway Mediates Neuronal Injury in an In Vitro Model of Ischemia-Reperfusion Insult

2021 ◽  
Author(s):  
Yaya Wang ◽  
Jie Zhang ◽  
Liqin Huang ◽  
Yanhong Mo ◽  
Changyu Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Brain ◽  
Pathophysiological Process ◽  
Vitro Model

Abstract Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.

Aberrant protein glycosylation in cancer: implications in targeted therapy

2021 ◽  
Author(s):  
Joana G. Rodrigues ◽  
Henrique O. Duarte ◽  
Celso A. Reis ◽  
Joana Gomes
Keyword(s):  
Targeted Therapy ◽  
Tumour Cell ◽  
Rational Design ◽  
Molecular Mechanisms ◽  
Clinical Performance ◽  
Therapeutic Strategies ◽  
Protein Glycosylation ◽  
Immune Checkpoints ◽  
Immunosuppressive Microenvironment ◽  
The Impact

Aberrant cell surface glycosylation signatures are currently known to actively drive the neoplastic transformation of healthy cells. By disrupting the homeostatic functions of their protein carriers, cancer-associated glycans mechanistically underpin several molecular hallmarks of human malignancy. Furthermore, such aberrant glycan structures play key roles in the acquisition of molecular resistance to targeted therapeutic agents, which compromises their clinical efficacy, by modulating tumour cell aggressiveness and supporting the establishment of an immunosuppressive microenvironment. Recent advances in the study of the tumour cell glycoproteome have unravelled previously elusive molecular mechanisms of therapeutic resistance, guided the rational design of novel personalized therapeutic strategies, and may further improve the clinical performance of currently approved anti-cancer targeted agents. In this review, we highlight the impact of glycosylation in cancer targeted therapy, with particular focus on receptor tyrosine kinase-targeted therapy, immune checkpoints blockade therapy, and current developments on therapeutic strategies directed to glycan-binding proteins and other innovative glycan therapeutic strategies.

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