**3. Results**

#### *3.1. Dataset of 32 UV-Induced Molecules*

We identified 32 unique molecules reported to be expressed after UV irradiation of cells and tissues (Table 1). There were 9 antimicrobial peptides (Supplementary Table S1), 10 cytokines, 6 growth factors, 3 enzymes, 2 transmembrane receptors, and 2 transcription regulators (Supplementary Table S2).

IPA analysis predicted that UV irradiation can induce molecules that are involved in innate and adaptive immune responses. IPA canonical pathway annotations of these 32 molecules (Table 1) were predicted to be associated with cellular stress and injury. This category included the wound healing signaling pathway (9/32, *<sup>p</sup>* = 3.22 × <sup>10</sup>−11). Annotations were also associated with cellular immune responses, and this category included the role of cytokines in mediating communication between immune cells (6/32, *<sup>p</sup>* = 8.74 × <sup>10</sup><sup>−</sup>11), communication between innate and adaptive immune cells (5/32, *<sup>p</sup>* = 7.44 × <sup>10</sup>−3), the Th1 and Th2 activation pathway (4/32, *<sup>p</sup>* = 8.01 × <sup>10</sup>−5), the Th1 pathway (3/32, *<sup>p</sup>* = 5.81 × <sup>10</sup><sup>−</sup>4), and the Th2 pathway (3/32, *<sup>p</sup>*= 8.13 × <sup>10</sup>−4). The top relevant pathway annotations are listed in Table 2 and all the relevant annotations ranked by their −log(*p* value) are listed in Supplementary Table S3. This list contains relevant

annotations within categories on cytokine signaling; growth factor signaling; intracellular and second messenger signaling; cellular growth, proliferation, and development; cellular immune response; and organismal growth and development.

**Table 2.** Ingenuity pathway analysis (IPA, Qiagen, Germantown, MD, USA) was used to assess whether the biomarkers in the literature dataset (*n* = 32) would participate in the activation of innate and immune mechanisms applicable to reducing endodontic infection, reducing inflammation, and assisting in endodontic tissue healing. Representative IPA canonical pathways annotations were associated with cellular stress and injury; cytokine signaling; cellular immune response. Representative IPA diseases or functions annotations were associated with antimicrobial response, cell-to-cell signaling and interaction, cellular movement, hematological system development and function, immune cell trafficking, and inflammatory response.




**Table 2.** *Cont.*

IPA disease and function annotations of these 32 molecules (Table 1) were predicted to be associated with innate and adaptive immune responses, applicable to reducing infection and inflammation and assisting in tissue healing. These included antimicrobial response, inflammatory response, cell-to-cell signaling and interaction, cellular movement, immune cell trafficking, cell death and survival, cellular growth and proliferation, cellular development, hematological system development and function, hematopoiesis, lymphoid tissue structure and development, tissue development, and tissue morphology. Examples of these functions are listed in Table 2 and all the relevant IPA disease and function annotations are listed in Supplementary Table S4.
