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Liquid Biopsies for Pancreatic Cancer: A Step Towards Early Detection
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Joseph Carmicheal, Rahat Jahan, Koelina Ganguly, Ashu Shah, Sukhwinder Kaur
Exosomes have been shown to have a multitude of functional properties exerting influence on many necessary cellular mechanisms, as well as those found in pancreatic cancer. Two of the most important of these functional capabilities are their role in intercellular communication [64] and the facilitation of the induction/ suppression of the immune response [65]. Costa-Silva et al. studied the ability of pancreatic cancer exosomes to form a pre-metastatic niche in the liver. Their group discovered that exosomes, originating from PC cells, cause Kupfer cells to secrete Transforming Growth Factor-β (TGF-β), thereby forming a fibrous microenvironment in the liver that is conducive to the propagation of metastases [66]. Additionally, tumor-derived exosomes have also been implicated in angiogenesis within the local tumor microenvironment [67] which has direct implications on tumor access to oxygen and nutrients. These particles have also been shown to modify the glucose uptake of cancer cells, thereby having a direct impact on metabolism and overall cell survival [68].
Radiation Hormesis in Immunity
Published in T. D. Luckey, Radiation Hormesis, 2020
A variety of cellular products are involved in defense mechanisms. The most studied are antibodies. Many small molecules are released into blood, lymph, or interstitial tissues for intercellular communication.974 These “cytocrines” include interferons, leukotrienes, and interleukins, as well as chemotactic, activating, and mitogenic factors.68,757 Metcalf found increased amounts of a serum lymphocyte-stimulating factor following low-dose irradiation of mice.613 This thymic hormone stimulates T cell maturation.527
Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
All cells possess a constitutive secretory pathway whereby vesicles that originate in the Golgi complex contain newly synthesized proteins (i.e., enzymes, growth factors, receptors, and extracellular matrix components) and carry them to the cell surface. Once there, the vesicles contact the plasma membrane and either release their content to the cell exterior (e.g., hormones or neurotransmitters), or their enclosed proteins become embedded within the plasma membrane (e.g., receptors). Neurons and endocrine/neuroendocrine cells are highly specialized cells that are dedicated to intercellular communication and store their chemical signals in committed secretory vesicles. Upon receiving appropriate stimuli, these cells release their content to the cell exterior by a calcium-regulated exocytosis.
The γH2AX DSB marker may not be a suitable biodosimeter to measure the biological MRT valley dose
Published in International Journal of Radiation Biology, 2021
Jessica A. Ventura, Jacqueline F. Donoghue, Cameron J. Nowell, Leonie M. Cann, Liam R. J. Day, Lloyd M. L. Smyth, Helen B. Forrester, Peter A. W. Rogers, Jeffrey C. Crosbie
The γH2AX foci yield reported in this study is comparable with earlier studies using mouse skin and fibroblasts (Rothkamm et al. 2012). Here we reported a yield of 5.9 ± 0.04 foci/cell/Gy for mouse skin and 27.4 ± 2.5 foci/cell/Gy for human fibroblasts following BB irradiation. The large yield differences between mouse skin and human fibroblast studies may be due to 1) the thickness of the paraffin embedded mouse skin sections was less than the diameter of nuclei therefore reducing overall foci count (Rothkamm et al. 2012), 2) different intercellular communication events in in vivo and in vitro studies, 3) difference in human versus mouse biology, 4) difference in radiosensitivity and proliferation capacity (Hall and Giaccia 2006), DNA repair kinetics (DiBiase et al. 2000), quantity of H2AX protein in chromatin (Rogakou et al. 1998; Nakamura et al. 2012), robustness of cellular defence processes including DNA repair efficiency (Song and Lambert 1999), and the antioxidant capacity or quantity of infiltrating immune cells (Redon et al. 2010). Conversely, the physical proximity of the cells on the glass could also account for the high levels of γH2AX foci in fibroblasts. Kegel et al reports that when cells grown on glass slides are irradiated with X-rays (photon energies below ∼60 keV) they exhibit higher levels of DSBs, due to the production of secondary electrons generated from irradiating the glass slide (Kegel et al. 2007).
Circulating extracellular vesicle content reveals de novo DNA methyltransferase expression as a molecular method to predict septic shock
Published in Journal of Extracellular Vesicles, 2019
Duaa A. Dakhlallah, Jon Wisler, Marieta Gencheva, Candice M. Brown, Erin R. Leatherman, Kanhaiya Singh, Kathy Brundage, Todd Karsies, Ahmad Dakhlallah, Kenneth W. Witwer, Chandan K. Sen, Timothy D. Eubank, Clay B. Marsh
Circulating EVs are subcellular plasma membrane-enclosed particles measuring 0.03–2 µm and shed during cellular activation and apoptosis by a complex budding mechanism. EVs can originate from almost all cell types, in vitro and in vivo [8–10]. An increasing number of laboratories have reported that EVs have specific functions and that their contents serve as instructions for the tissue microenvironment which takes up these EVs, or when released into the systemic circulation under certain conditions [11]. EVs contain proteins and nucleic acids, including small regulatory RNA molecules (miRNAs), which are important in the regulation of gene expression [12,13]. These important findings demonstrate that EVs contain and can deliver epigenetic regulators to proximal or distal recipient cells and can influence the behaviour of targeted cells at both molecular and signalling levels. This phenomenon has opened a new era in the field of intercellular communication and resultant phenotype changes observed in pathophysiology, pathology, cell biology, diagnosis, and therapeutics. For example, EVs can transfer receptors, proteins, and cytokines to stimulate and change signalling complexes, directly. At the same time, they can carry regulatory messages (miRNAs and nucleic acids) to alter gene expression and protein production at the molecular level [13].
Gingival epithelial barrier: regulation by beneficial and harmful microbes
Published in Tissue Barriers, 2019
Naoki Takahashi, Benso Sulijaya, Miki Yamada-Hara, Takahiro Tsuzuno, Koichi Tabeta, Kazuhisa Yamazaki
A primarily structural bond between epithelial cells is created by junctional molecules, including tight junctions, adherens junctions, and gap junctions8,26 (Figure 1). Tight junctions are responsible for paracellular transport of ions, water, and solutes due to their semipermeable structure.28 Several proteins are found in the tight junctions, such as occludin,29 claudins,30 and zonula occludens (ZO) protein ZO-1, ZO-2, and ZO-3.30–32 Occludin has been detected in the gingival epithelium’s surface layer, whereas claudin-1 was found in the uppermost layer.26 Claudins have barrier properties, which directly regulate gate function at paracellular tight junction channels.30 Adherens junctions play a vital role in controlling the junctional complex activity.8 Adherens junctions are cell-to-cell adhesion sites where the actin-based cytoskeleton and cytoplasmic components are constructed, also known as the classic cadherins function.33 The intercellular communication in gap junctions is involved in homeostasis, regeneration, and developmental processes.34 Furthermore, gap junctions regulate the reciprocal exchange of metabolites and ions of molecular weight ≤1 kDa, such as cyclic adenosine monophosphate and Ca,35+ between adjacent cells. The form of this junction is a head-to-head docking of hexameric structures called connexons, and membrane proteins called connexins.36