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Genetic Studies of PTSD and Substance Use Disorders
Published in Anka A. Vujanovic, Sudie E. Back, Posttraumatic Stress and Substance Use Disorders, 2019
Christina M. Sheerin, Leslie A. Brick, Nicole R. Nugent, Ana B. Amstadter
Opioids and stimulants. Relatively fewer GWA studies have been conducted using opioid or stimulant phenotypes (e.g., cocaine, methamphetamine), compared to other licit psychoactive substances, despite evidence for their heritability (see review by Jensen, 2016). Significant effects have been observed for opioid dependence in a sample of 3,627 with genome-wide significance for a SNP in NCK2, an adaptor protein associated with growth factor receptors that may also be associated with nicotine dependence (Liu, Guo, Jiang, & Zhang, 2013). Another GWAS that included a meta-analysis with an independent sample (N = 5,697) identified four regions containing SNPs that passed genome-wide significance, including potassium voltage-gated channel genes KCNG2 and KCNC1, as well as APBB2 and PARVA genes to be associated with opioid dependence symptom count (Gelernter, Kranzler, Sherva, Koesterer, et al., 2014). More recently, a meta-analysis evidenced a difference between opioid-dependent individuals and opioid misusers who never progressed to daily injection for a SNP in CNIH3, associated with the glutamate neurotransmitter system (Nelson et al., 2016; discovery N = 1,328; two replication sets totaling N = 1,309). Finally, one study examining opioid (i.e., heroin) dependence in a sample of 325 methadone-stabilized, former addicts and 250 control participants did not find any variants that reached genome-wide significance (Nielsen et al., 2010).
Expression and clinicopathological significance of Nck1 in human astrocytoma progression
Published in International Journal of Neuroscience, 2019
Ravindra Pramod Deshpande, Manas Panigrahi, Chandra Sekhar Y.B.V.K, Phanithi Prakash Babu
Nck (non-catalytic region of tyrosine kinase) family constitutes two members, Nck1 and Nck2. These signaling proteins located in cytoplasm-containing Src homology 2 and 3 domains [11]. Nck proteins are associated with receptor tyrosine kinases and regulate actin cytoskeleton dynamics including neuronal migration [12, 13]. Furthermore, Nck1 is found to modulate endoplasmic reticulum stress associated signaling by regulating the activity of eukaryotic initiation factor 2 alpha [14] and also reported to promote cell migration by associating with dermcidin in hepatocellular carcinoma [15].
Targeting regulation of the tumour microenvironment induces apoptosis of breast cancer cells by an affinity hemoperfusion adsorbent
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2021
Lichun Wang, Jian Chen, Yamin Chai, Wenyan Han, Jie Shen, Nan Li, Jinyan Lu, Yunzheng Du, Zhuang Liu, Yameng Yu, Jingzhe Dong, Lailiang Ou
In order to evaluate the effect of perfusion at the level of gene expression of SHZ-88 cells, mRNA microarray assays were performed after 72 h exposure. As shown in Figure S9, we identified 954 significantly differentially expressed genes by setting the absolute fold change threshold to >1.2 and the p-value at <.05. It can be seen from the cluster gram that the samples from the two groups are clearly separated, which indicates a robust response to PVA-H perfusion treatment. Among these 954 differentially expressed genes, 420 genes were downregulated and 534 genes were upregulated. It is worth noting that in Figure S10, we had further chosen to focus on genes involved in proliferation and apoptosis. Figure 5(a), Tables S5 and S6 showed the genes related to positive and negative regulation of proliferative and apoptotic. Genes positively regulating proliferating were down-regulated (light blue), while those negatively regulating proliferation were up-regulated (red). Genes positively regulating apoptosis were up-regulated (red), while those negatively regulating apoptosis were down-regulated (light blue). Thus, as for the functionally significantly related genes involved in the proliferative and apoptotic functions (Figure 5(b)), on the basis of related research, not only the down-regulated genes, such as gene Timp3, Ppargc1a, Lep and Nck2, but also the up-regulated genes, such as gene Blm, Rag1, Lifr and Ptk2b, would promote apoptosis of breast cancer cells [22–31]. More importantly, both the down-regulated genes, such as gene Mmp12, Cxcl1, Lep and Wnt10b, and the up-regulated genes, such as gene Gpc3, Miip, Ovol1 and Fhl1, would inhibit the proliferation of breast cancer cells [27,28,32–41]. Taken together, these results imply that most genes involved in proliferation and apoptosis were changed in such a manner that they exhibited a positive tendency to inhibit proliferation and promote apoptosis of the breast cancer cells after treatment by the perfusion through PVA-H microspheres.