Early life complications, placental genomics, and risk for neurodevelopmental disorders in offspring
Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos in New Technologies and Perinatal Medicine, 2019
A preliminary expression quantitative trait loci (eQTL) analysis in placenta has detected an enrichment of SNPs associated with schizophrenia among the genetic variants that predict gene expression in placenta (68). Consistently, it has been found in multiple independent data sets that the genes in the schizophrenia risk loci tend to be differentially expressed, and specifically upregulated, in placentae from complicated pregnancies compared with controls, and in male compared with female placentae (55). In the same study, placental transcriptome data have been employed to calculate a measure of placenta genomic risk for schizophrenia (PlacPRS) based on schizophrenia risk loci containing genes highly and differentially expressed in placentae, and a measure of genomic risk based on the remaining loci (NonPlacPRS). Interestingly, the PlacPRSs specifically interact with ELCs in affecting risk for schizophrenia, while the NonPlacPRSs do not. These results suggest that the study of placental transcriptome may help to identify a specific component of genomic risk that is linked to etiopathogenetic mechanisms acting in placenta. Pathway analyses further revealed that the PlacPRS genes are involved in cellular stress response and are coexpressed with inflammatory/immune response genes, while the NonPlacPRS genes implicate orthogonal and more traditionally brain-related biological processes (e.g., synaptic function) (55).
Reductionism versus Systems Thinking in Aging Research
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Another possible bridge between reductionism and systems thinking may be found in a cybernetic view of aging, one that also considers a human organism as a “whole,” that is, an autonomous entity that interacts and depends on its environment in a “wholistic” manner (Figure 31.3). In this respect, it is necessary to consider the concept of “homeodynamic space” developed by biogerontologist Suresh Rattan. This virtual space indicates the limits of the survival ability and buffering capacity of any dynamic biological system. Aging is associated with shrinkage of, or dysfunctions within, this space [53]. Associated with this concept is the general concept of hormesis and the cellular stress response. Hormesis is a process defined by a nonlinear, “U”-shaped, “low dose stimulation, high dose inhibition” principle (see Reference 54), whereby exposure to a weak stimulus may positively challenge the organism by upregulating the stress response and result in health benefits, whereas an excessive, suboptimal, or prolonged exposure can result in damage and disease. The concept of hormesis is based on mild exposures to new environmental information, a continual though not excessive state of “novelty” which modulates the homoeostatic mechanisms and redefines the homeodynamic space. The hormetic response is triggered by exposure to any physical, chemical, biological, mental, or other challenges, which may disturb the cellular or organismic homeostatic mechanisms. Hormesis is invoked when one operates at the “outer edge of their comfort zone,” when the stimulus confronting them is challenging but “doable.” This, translated into clinical, practical terms, should mean “positive stress”: frustrating but in a pleasant, positive way, which provokes rather than annoys.
Reconciling two opposing effects of radiation therapy: stimulation of cancer cell invasion and activation of anti-cancer immunity
Published in International Journal of Radiation Biology, 2023
Ayman Oweida, Benoit Paquette
Radiation can induce the secretion of a plethora of chemokines that attract effector T cells. This occurs as part of the cellular stress response that is most commonly regulated by NFκB (Liu et al. 2017). Matsumura S et al. showed that radiation induces the release of CXCL16 by breast cancer cells and this was sufficient to attract effector T cells leading to tumor regression (Matsumura et al. 2008). Harlin et al. found that the presence of effector T cells correlated with the expression of several well-established lymphocyte chemokines including CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10 (Harlin et al. 2009). The presence of the corresponding chemokine receptors was validated on CD8+ effector T cells. Using transwell migration assays, the authors confirmed the ability of each of these chemokines to promote migration of CD8+ effector cells in vitro.
Study on the mechanism of treating COVID-19 with Shenqi Wan based on network pharmacology
Published in Drug Development and Industrial Pharmacy, 2021
Xian-wen YE, Ya-ling Deng, Xia Zhang, Min-min Liu, Ying Liu, Ya-ting Xie, Quan Wan, Min Huang, Tao Zhang, Jia-he Xi, Jin-lian Zhang
PPI enrichment analysis was carried out using the following databases: BioGrid, InWeb-IM, and OmniPath used the MCODE algorithm to identify tightly connected network nodes. The MCODE network determined by the common target is shown in Figure 5. KEGG pathway and GO biological function enrichment analysis were applied to each MCODE node, and the three items with the highest score were calculated according to the p value. As can be seen from Figure 5, the clustering of common targets can be divided into two categories: in the first category (red), GO and KEGG pathway are the response of reactive oxygen species to inorganic substances, the response of cells to organic nitrogen compounds, the AGE-RAGE signaling pathway in diabetic complications, and toxoplasmosis, Hepatitis C. In the second category (blue), the stress response to lipopolysaccharide, the response to bacterial molecules, response to molecule of bacterial origin, second messenger mediated signaling, Toll-like receptor signaling, legionellosis, and RIG-I-like receptor signaling pathway. From the above results, the common targets are mainly involved in cellular stress response and receptor signal pathway.
Neuroprotective effects of rutin on ASH neurons in Caenorhabditis elegans model of Huntington’s disease
Published in Nutritional Neuroscience, 2022
Larissa Marafiga Cordeiro, Marcell Valandro Soares, Aline Franzen da Silva, Marina Lopes Machado, Fabiane Bicca Obetine Baptista, Tássia Limana da Silveira, Leticia Priscilla Arantes, Felix Alexandre Antunes Soares
The DAF-16 transcription factor, a C. elegans homolog of mammalian Forkhead box (FOXO), is thought to be the main target of DAF-2, an insulin/insulin-like growth factor (IGF)-1 receptor homolog [47]. Previous studies reported that DAF-16 plays a pivotal role in the regulation of longevity, and is also involved in the formation of less toxic, high-molecular-weight protein aggregates [48], via the activation of antioxidant genes and chaperones, thereby ameliorating polyQ aggregation and toxicity [49]. Our previous study demonstrated rutin-induced nuclear translocation of the DAF-16/FOXO transcription factor in C. elegans [7], which is essential for activating downstream genes. Under stress, DAF-16 proteins are phosphorylated and activated, and accumulate in the nucleus, thereby activating own functions to regulate downstream target genes, such as sod-3, which play an important role in metabolism, oxidative stress, and aging [50]. Genetic analysis has shown that DAF-16 is one of the essential transcriptional activators for a subset of chaperones, especially HSP-16.2. HSP-16.2 plays a protective role in polyQ diseases, as it promotes folding/refolding of proteins into appropriate conformations, and recovers previously aggregated proteins [51]. Molecular chaperones are also evolutionarily conserved in the cellular response to stress, and in the regulation of longevity, and some studies show a direct role of these components in the cellular stress response associated with the regulation of lifespan [52].
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