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Topic Review
Cellular Senescence in the Lung
Cellular senescence is a key process in physiological dysfunction developing upon aging or following diverse stressors including ionizing radiation. It describes the state of a permanent cell cycle arrest, in which proliferating cells become resistant to growth-stimulating factors. Senescent cells differ from quiescent cells, which can re-enter the cell cycle and from finally differentiated cells: morphological and metabolic changes, restructuring of chromatin, changes in gene expressions and the appropriation of an inflammation-promoting phenotype, called the senescence-associated secretory phenotype (SASP), characterize cellular senescence. The biological role of senescence is complex, since both protective and harmful effects have been described for senescent cells. While initially described as a mechanism to avoid malignant transformation of damaged cells, senescence can even contribute to many age-related diseases, including cancer, tissue degeneration, and inflammatory diseases, particularly when senescent cells persist in damaged tissues. Due to overwhelming evidence about the important contribution of cellular senescence to the pathogenesis of different lung diseases, specific targeting of senescent cells or of pathology-promoting SASP factors as potential therapeutic approach has been suggested. In this review, we summarize recent advances regarding the role of cellular (fibroblastic, endothelial, and epithelial) senescence in lung pathologies, with a focus on radiation-induced senescence. Among the different cells here, a central role of epithelial senescence is suggested.
  • 926
  • 29 Oct 2020
Topic Review
Hyperthermia
Hyperthermia is one of the severe acute adverse effects that can be caused by the ingestion of recreational drugs, such as methcathinones. The effect of hyperthermia on neurotoxicity is currently not known. The primary aim of our study was therefore to investigate the effects of hyperthermia (40.5 °C) on the neurotoxicity of methcathinone (MC), 4-chloromethcathinone (4-CMC), and 4-methylmethcathinone (4-MMC) in SH-SY5Y cells. We found that 4-CMC and 4-MMC were cytotoxic (decrease in cellular ATP and plasma membrane damage) under both hyper- (40.5 °C) and normothermic conditions (37 °C), whereby cells were more sensitive to the toxicants at 40.5 °C. 4-CMC and 4-MMC impaired the function of the mitochondrial electron transport chain and increased mitochondrial formation of reactive oxygen species (ROS) in SH-SY5Y cells, which were accentuated under hyperthermic conditions. Hyperthermia was associated with a rapid expression of the 70 kilodalton heat shock protein (Hsp70), which partially prevented cell death after 6 h of exposure to the toxicants. After 24 h of exposure, autophagy was stimulated by the toxicants and by hyperthermia but could only partially prevent cell death. In conclusion, hyperthermic conditions increased the neurotoxic properties of methcathinones despite the stimulation of protective mechanisms. These findings may be important for the understanding of the mechanisms and clinical consequences of the neurotoxicity associated with these compounds.
  • 783
  • 29 Oct 2020
Topic Review
Periodontitis Treatment
Fabrication of biomaterial that mimics a suitable biological microenvironment is still a major challenge in the field of periodontitis treatment. Hence, in this report, we presented for the first time the fabrication of a novel biomaterial 3D matrix using collagen combined with sodium alginate and titanium oxide (TiO2) to recreate the in-vivo microenvironment and to act as a platform for the culture of human periodontal ligament fibroblasts (HPLF) towards osteogenic differentiation.
  • 846
  • 29 Oct 2020
Topic Review
Tendon and Mast Cells
Understanding the links between the tendon healing process, inflammatory mechanisms, and tendon homeostasis after tissue damage is crucial in developing novel therapeutics for human tendon disorders. The inflammatory mechanisms that are operative in response to tendon injury are not fully understood, but it has been suggested that inflammation occurring in response to nerve signaling, i.e., neurogenic inflammation, has a pathogenic role. In this review, we discuss the role of mast cells in the communication with peripheral nerves, and their emerging role in tendon healing and inflammation after injury.
  • 978
  • 29 Oct 2020
Topic Review
Scribble Polarity Module in Neuroblasts
The Scribble polarity module is composed by Scribble (Scrib), Discs large 1 (Dlg1) and Lethal (2) giant larvae (L(2)gl), a group of highly conserved neoplastic tumor suppressor genes (TSGs) from flies to humans. Even though the Scribble module has been profusely studied in epithelial cell polarity, the number of tissues and processes in which it is involved is increasingly growing. Here we discuss the role of the Scribble module in the asymmetric division of Drosophila neuroblasts (NBs), as well as the underlying mechanisms by which those TSGs act in this process. Finally, we also describe what we know about the consequences of mutating these genes in impairing the process of asymmetric NB division and promoting tumor-like overgrowth.
  • 943
  • 29 Oct 2020
Topic Review
Endoplasmic Reticulum Stress Sensor IRE1α
Inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) is the most prominent and evolutionarily conserved unfolded protein response (UPR) signal transducer during endoplasmic reticulum functional upset (ER stress). A IRE1α signal pathway arbitrates yin and yang of cellular fate in objectionable conditions. It plays several roles in fundamental cellular physiology as well as in several pathological conditions such as diabetes, obesity, inflammation, cancer, neurodegeneration, and in many other diseases.
  • 689
  • 29 Oct 2020
Topic Review
PDE2A for Mouse Liver Development
cAMP and cGMP are intracellular signaling molecules produced in response to a plethora of extracellular signals in order to coordinate cellular metabolism, proliferation, differentiation and apoptosis. Phosphodiesterases (PDEs) are the enzymes that hydrolyze cAMP and cGMP in order to end or to limit the responses to these signals. To date 11 PDE families (named PDE1 to PDE11) have been identified across each cell type expressed in a peculiar pattern. They enclose 21 genes that codify approximately 100 enzymes that form a redundant network ensuring the compensation of activity in case of alteration of activity or lack of expression of one of the members. PDE2A, a cAMP-hydrolyzing enzyme, represents the exception to this picture, as PDE2A knockout is embryonic lethal. Knockout embryos show that the lack of the enzyme has the greatest impact on the development of the heart and of the liver, which is no longer able to assume its hematopoietic role. The increase of the intracellular cAMP level and the downregulation of the anti-apoptotic gene Bcl2 might explain the loss of integrity in the PDE2A knockout liver niche that compromises the hematopoietic function and maturation.
  • 743
  • 29 Oct 2020
Topic Review
RNA-Binding Proteins Regulating
The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. The post-transcriptional regulation of lncRNAs is mediated by RNA-binding proteins (RBPs). Interestingly, RBPs themselves are commonly deregulated in cancer and could thus constitute a major contribution to the deregulation of cancer-associated lncRNAs. Discussed here are four examples of well-known RBPs that regulate the transport or localization of cancer-associated lncRNAs and thereby impact the functionality of these lncRNAs. So far, out of the vast number of RBPs that exist, only a relatively small number has been found to specifically guide the transport or localization of cancer-related lncRNAs. In general, there is still a lack of knowledge about how lncRNAs are shuttled between or retained within different cellular compartments and future research will have to shed more light on these regulatory mechanisms.
  • 856
  • 29 Oct 2020
Topic Review
Therapeutic Stem Cell Banks
Stem cells are currently being used in many clinical trials for regenerative purposes. These are promising results for stem cells in the treatment of several diseases, including cancer. Nevertheless, there are still many variables which should be addressed before the application of stem cells for cancer treatment. One approach should be to establish well-characterized therapeutic stem cell banks to minimize the variation in results from different clinical trials and facilitate their effective use in basic and translational research. 
  • 560
  • 27 Oct 2020
Topic Review
Melanogenesis
Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that convert tyrosine to form brown-black eumelanin and yellow-red pheomelanin within melanosomal compartments in melanocytes, following the cascades of events interacting with a series of autocrine and paracrine signals. Fully melanized melanosomes are delivered to keratinocytes of the skin and hair. In humans, eumelanin and pheomelanin are mixed together regardless of the pigmentary phenotype. The ratio of the two melanin pigments is determined by race and/or specific genetic variations. On the other hand, many mammals have various patterns of hair coat color that can be changed temporally. Wild type mice have agouti pattern hair caused by a mechanism, called pigment-type switching.
  • 8.3K
  • 27 Oct 2020
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