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. 2021 Feb 9;2021:6664453. doi: 10.1155/2021/6664453

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Copyright © 2021 Qian Yang et al.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PMC Copyright notice

(a) LIUS modulates oxidative stress-related gene expressions (reactive oxygen species, ROS, and regulatome). Three out of a total of 84 (3.70%) oxidative stress genes (ROS regulatome) were upregulated in lymphoma cells (L) and bone marrow cells (B). Gpx3 was shared in L and B. Two out of a total of 84 genes (2.47%) were downregulated in bone marrow cells (B). No oxidative stress gene expressions were changed in the preosteoblast microarray dataset. (b) LIUS modulates the ROS regulatome in a cell-specific manner. (c) The Ingenuity Pathway Analyses (IPA) of ROS dependence to LIUS-modulated innatomic genes in three types of cells were summarized into four groups: (1) the ROS-promoted group, (2) the ROS-suppressed group, (3) the ROS-dependent/suppressed pathway-uncertain group, and (4) the ROS-independent group. These results demonstrated that LIUS-modulated innatomic genes were significantly mediated by ROS-promoted or ROS-suppressed pathways in bone marrow cells, which were higher than those of LIUS-modulated innatomic genes in lymphoma cells. In addition, the IPA-identified significant pathway numbers in bone marrow cells that were significantly higher than those of lymphoma cells, suggesting that ROS-modulated genes in lymphoma cells are much more diversified in the pathways than those of bone marrow cells (see supplemental Tables 17A-17F for details). (d) LIUS-modulated innatomic genes were classified into four groups, namely, (1) the ROS-promoted group, (2) the ROS-suppressed group, (3) the uncertain (not shown) group, and (4) the ROS-independent group, based on their expression changes in ROS-generating enzyme NOX2 KO microarrays and antioxidant transcription factor Nrf2 KO microarrays. (e) Six ROS-promoted pathways were involved in LIUS-upregulated genes in bone marrow cells. (f) Three ROS-suppressed pathways were involved in LIUS-upregulated genes in bone marrow cells. (g) The top 10 of a total of 31 ROS-promoted pathways were involved in LIUS-downregulated genes in bone marrow cells. (h) Only one ROS-suppressed pathway was involved in LIUS-downregulated genes in bone marrow cells. (I) Only one ROS-suppressed pathway was involved in LIUS-upregulated genes in lymphoma cells. (j) LIUS modulates innatome via reactive oxygen species (ROS) pathways mediated by pro-ROS generation enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) (PMIDs: 21629295; 28916473) and antioxidant transcription factor nuclear erythroid-2 like factor (Nrf2) (PMID: 30610225).