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Introduction: Photodynamic therapy (PDT) is a combined method of light and light-activated chemicals that are called photosensitizers (PSs). PDT is recommended as a high cure rate method with fewer side effects and a noninvasive tool to treat cancer. This study aimed to evaluate PDT efficacy as a therapeutic method against actinic keratoses in patients via protein-protein interaction (PPI) network analysis by using the gene expression profiles of Gene Expression Omnibus (GEO). Methods: Twenty-one gene expression profiles were extracted from GEO and analyzed by GEO2R to determine the significant differentially expressed genes (DEGs). The significant DEGs were included in PPI networks via Cytoscape software. The networks were analyzed by the "Network Analyzer", and the elements of the main connected components were assessed. Results: There were three main connected components for the compared sets of the gene expression profiles including the lesional region of skin before (Before set) and after (After set) PDT versus healthy (healthy set) skin and before versus after. The before-health comparison showed a partial similarity with the After-Healthy assessment. The before-after evaluation indicated that there were not considerable differences between the gene expression profile of the lesional region before and after PDT. Conclusion: In conclusion, PDT was unable to return the gene expression pattern of the actinic keratoses skin to a healthy condition completely., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2023 J Lasers Med Sci.)

Introduction: Photodynamic therapy (PDT) is a method based on the application of a photosensitive agent and the administration of light irradiation on the treated samples. PDT is applied as an effective tool with minimal side effects against tumor tissues. This study aimed to assess the targets of critical genes by PDT at the cellular level of cancer to provide a new perspective on its molecular mechanism. Methods: To assess the effect of PDT, we extracted the differentially expressed genes (DEGs) from the gene expression profiles of human umbilical vein endothelial cells (HUVECs) treated with PDT from Gene Expression Omnibus (GEO) databases. The queried DEGs were evaluated via a regulatory network and gene ontology enrichment to find the critical targets. Results: Among 76 queried significant DEGs, 27 individuals were interacted by activation, inhibition, and co-expression actions. Thirty DEGs were related to the five classes of biological terms. The IL-17 signaling pathway and PTGS2, CXCL8, FOS, JUN, CXCL1, ZFP36, and FOSB were identified as the crucial targets of PDT. Conclusion: PDT as a stimulator of gene expression and an activator of gene activity overexpressed and hyper-activated many genes. It seems that PDT introduces a number of genes and pathways that can be regulated by anticancer drugs to fight against cancers., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 J Lasers Med Sci.)

Introduction: Circadian rhythms refer to daily cyclic events such as activity and rest in biology. A protein-based core related to the mechanism of circadian is identified. In the present study, the gene expression profiles of mouse skin in different conditions of light-dark times were investigated via protein-protein interaction (PPI) analysis to explore the main affected genes. Methods: GSE174155 was derived from Gene Expression Omnibus (GEO) and was analyzed via GEO2R to find the significant differentially expressed genes (DEGs). The gene expression profiles of Cry-null (genotype: cryptochrome-1(-/-): crytochrome-2 (-/-)) mouse skin versus the wild-type samples in the various circadian times (CTs) were assessed. The queried DEGs plus 50 first neighbors were included in a PPI network via the STRING database by Cytoscape software. The networks were analyzed and the central nodes were evaluated. Results: Three groups of mice based on CTs were identified. 15, 15, and 14 central nodes were determined as central nodes for the analyze networks. There was not a common central node for the analyzed networks. Conclusion: It was pointed out that the light/dark time ratio had a gross effect on the gene expression profile of the skin in the mice. Results imply more investigations to suggest a standard protocol related to CT, considering human lifestyle and exploring suitable protective methods for the jobs which are fixed in the abnormal CT sets., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 J Lasers Med Sci.)

Introduction: Conventional fractionation (CF) and hypofractionation (HF) are two radiotherapy methods against cancer, which are applied in medicine. Understanding the efficacy and molecular mechanism of the two methods implies more investigations. In the present study, proteomic findings about the mentioned methods relative to the controls were analyzed via network analysis. Methods: The significant differentially expressed proteins (DEPs) of prostate cancer (PCa) cell line DU145 in response to CF and HF radiation therapy versus controls were extracted from the literature. The protein-protein interaction (PPI) networks were constructed via the STRING database via Cytoscape software. The networks were analyzed by "NetworkAnalyzer" to determine hub DEPs. Results: 126 and 63 significant DEPs were identified for treated DU145 with CF and HF radiation respectively. The PPI networks were constructed by the queried DEPs plus 100 first neighbors. ALB, CD44, THBS1, EPCAM, F2, KRT19, and MCAM were highlighted as common hubs. VTM, OCLN, HSPB1, FLNA, AHSG, and SERPINC1 appeared as the discriminator hub between the studied cells. Conclusion: 70% of the hubs were common between CF and HF conditions, and they induced radio-resistance activity in the survived cells. Six central proteins which discriminate the function of the two groups of the irradiated cells were introduced. On the basis of these findings, it seems that DU145-CF cells, relative to the DU145-UF cells, are more radio-resistant., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 J Lasers Med Sci.)

Introduction: Understanding the molecular mechanism of chronic low-dose ionizing radiation (LDIR) effects on the human body is the subject of many research studies. Several aspects of cell function such as cell proliferation, apoptosis, inflammation, and tumorigenesis are affected by LDIR. Detection of the main biological process that is targeted by LIDR via network analysis is the main aim of this study. Methods: GSE66720 consisting of gene expression profiles of human umbilical vein endothelial cells (HUVECs) (a suitable cell line to be investigated), including irradiated and control cells, was downloaded from Gene Expression Omnibus (GEO). The significant differentially expressed genes (DEGs) were determined and analyzed via protein-protein interaction (PPI) network analysis to find the central individuals. The main cell function which was related to the central nodes was introduced. Results: Among 64 queried DEGs, 48 genes were recognized by the STRING database. C-X-C motif chemokine ligand 8 (CXCL8), intercellular adhesion molecule 1 (ICAM1), Melanoma growth-stimulatory activity/growth-regulated protein α (CXCL1), vascular cell adhesion molecule 1 (VCAM-1), and nerve growth factor (NGF) were introduced as hub nodes. Conclusion: Findings indicate that inflammation is the main initial target of LDIR at the cellular level which is associated with alteration in the other essential functions of the irradiated cells., Competing Interests: All authors declare they have no conflicts of interest., (Copyright © 2022 J Lasers Med Sci.)

Introduction: Low-level laser radiation has a significant effect on cell proliferation. Various investigations into the effect of Er: YAG laser on the treated cell lines have been published. Determining core targeted proteins is an attractive subject. This research aimed at identifying the critical targeted protein by a low-level Er: YAG laser in primary osteoblast-like cells. Methods: Data were extracted from the literature about proteomic assessment of 3.3 J/cm 2 of low-level Er: YAG laser radiation on osteoblast-like cells of rat calvaria. The significant differentially expressed proteins plus 100 first neighbors were analyzed via network analysis and gene ontology enrichment. Results: Nine differentially expressed proteins among the 12 queried proteins were included in the main connected component. Analysis revealed that Cxcl1 was a key targeted protein in response to laser radiation. The presence of Cxcl1 in the significant cellular pathways indicated that cell growth and proliferation were affected. Conclusion: It can be concluded that the immune system is affected by the laser to activate cellular defense against stress., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2022 J Lasers Med Sci.)

Introduction: Diverse microbiotas which have some contributions to gene expression reside in human skin. To identify the protective role of the skin microbiome against UV exposure, proteinprotein interaction (PPI) network analysis is used to assessment gene expression alteration. Methods: A microarray dataset, GEO accession number GSE117359, was considered in this respect. Differential expressed genes (DEGs) in the germ-free (GF) and specific pathogen-free (SPF) groups are analyzed by GEO2R. The top significant DEGs were assigned for network analysis via Cytoscape 3.7.2 and its applications. Results: A total of 28 genes were identified as significant DEGs and the centrality analysis of the network indicated that only one of the seven hub-bottlenecks was from queried genes. The gene ontology analysis of Il6, Cxcl2, Cxcl1, TNF, Il10, Cxcl10, and Mmp9 showed that the crucial genes were highly enriched in the immune system. Conclusion: The skin microbiome plays a significant role in the protection of skin against UV irradiation and the role of TNF and IL6 is prominent in this regard., (Copyright © 2020 J Lasers Med Sci.)

Objective: The purpose of this study is to investigate the effects of low-power lasers on kidney disease by investigating several studies. Methods: A number of articles from 1998 to 2019 were chosen from the sources of PubMed, Scopus, and only the articles studying the effect of low-power lasers on kidney disease were investigated. Results: After reviewing the literature, 21 articles examining only the effects of low-power lasers on kidney disease were found. The results of these studies showed that the parameter of the lowpower laser would result in different outcomes. So, a low-power laser with various parameters can be effective in the treatment of kidney diseases such as acute kidney disease, diabetes, glomerulonephritis, nephrectomy, metabolic syndrome, and kidney fibrosis. Most studies have shown that low-power lasers can affect TGFβ1 signaling which is the most important signaling in the treatment of renal fibrosis. Conclusion: Lasers can be effective in reducing or enhancing inflammatory responses, reducing fibrosis factors, and decreasing reactive oxygen species (ROS) levels in kidney disease and glomerular cell proliferation., (Copyright © 2020 J Lasers Med Sci.)

Introduction: The human melanoma is a type of invasive tumor the treatment of which is challenging. To better understand the proton irradiation mechanisms as one of the widely applied therapy for this type of cancer, bioinformatics analysis of proteomics outcome could be beneficial. Methods: Protein-protein interaction network analysis of the differentially expressed proteins (DEPs) of melanoma BLM (BRO lung metastasis) cells in the treatment of 3 Gy dosage proton therapy was performed in this study via Cytoscape V.3.7.2. and its integrated plug-ins. Results: Eighteen DEPs were searched for network constructions and limited numbers of query +neighbor proteins were found central. The hub-bottlenecks (i.e. central nodes) were GAPDH, ACTB, ALB, AKT1, TP53, and EGFR. The fist mentioned proteins were from DEPs. The enrichment analysis of these elements identified nitric-oxide synthase regulator activity and the positive regulation of the norepinephrine uptake that may be the key to the mechanisms of proton therapy. Conclusion: In conclusion, the identified central nodes (EGFR, TP53, ALB, AKT1, GAPDH, and ACTB) and the related biological terms are the critical affected genes and biological terms in the irradiated melanoma cells., (Copyright © 2019 J Lasers Med Sci.)

Introduction: N Exposure to artificial light at night (LAN) affects human health and causes several functional modifications in the body. Obesity, diabetes, and hormonal changes are reported after exposure to LAN in humans. This study aims to highlight the critical features of biological terms that are affected in the liver of rats which received autonomic nervous system denervation. Methods: The liver gene expression profiles of 8 male Wistar rats that received sympathetic plus parasympathetic hepatic denervation and were exposed to LAN from Gene Expression Omnibus (GEO) for 1 hour were compared with 5 controls. The significant differentially-expressed genes (DEGs) were screened by the protein-protein interaction (PPI) network analysis STRING database (an application of Cytoscape software). Also, CuleGO and CleuDedia, the 2 applications of Cytoscape software, were used for more analysis. Results: Among 250 DEGs, 173 characterized genes with fold change more than 2 plus 100 added relevant genes were included in the PPI network. The analysis of the main connected component (MCC) led to introducing 15 hubs and 15 bottlenecks. CCT2, COPS7A, KAT2A, and ERCC1 were determined as hub-bottlenecks. Among hubs and bottlenecks, DHX15, KAT2A, CCT2, HSP90AB1, CCNE1, DHX16, LSM2, WEE1, CWC27, BAZ1B, RAB22A, DNM2, and DHX30 were linked to each other by various kinds of actions. CCT2 and KAT2A, the 2 hub-bottlenecks, were included in the interacted genes in the action map. Four classes of biological terms including negative regulation of non-motile cilium assembly, negative regulation of transforming growth factor beta activation, alpha-tubulin acetylation, and histamine-induced gastric acid secretion were identified as the critical biochemical pathways and biological processes. Conclusion: Several essential functions such as differentiation, cell cycle, ribosome assembly, and splicing are affected by LAN in rat livers with autonomic nervous system denervation., (Copyright © 2019 J Lasers Med Sci.)

Introduction: In sports medicine, laser application has been well-established for the recovery of muscles. The mechanisms by which benefits of this kind of therapy can be studied is molecular research approach. Protein-protein interaction network analysis as one of the important complementary studies of proteomics can accelerate this goal by the identification of novel contributing markers. Methods: By the use of Cytoscape V3.7.1 and its applications, a network of differential expressed proteins (DEPs) from IR laser treatment samples were constructed and analyzed. Six hub-bottlenecks were determined, 4 of which were from differentially expressed proteins. Results: ClueGO discovered 4 biological processes related to these hub-bottlenecks that their function could alter due to IR laser therapy. Conclusion: In fact, by the expression changes of hub-bottlenecks including the up-regulation of HSP90s, one of the prominent biological processes in muscle recovery could be activated. This process is called nitric oxide synthase (NOS) activation that could be proposed as one of the underlying mechanisms of IR laser treatments in muscle recovery., (Copyright © 2019 J Lasers Med Sci.)

Introduction: Application of laser in medicine and cosmetic purposes has raised grossly in recent years. There are contradictory finding about its side effects. In this research critical differentially expressed proteins after irradiation erbium:yttrium-aluminum-garnet (Er:YAG) laser on skin are investigated. Methods: Proteome data including 31 proteins were obtained from a proteomics investigation of laser irradiation, Er:YAG on female mouse skin that are published by Pan et al. The query proteins and 100 related ones were included in the protein-protein interaction (PPI) network. The central nodes were determined and all of nodes were included in action maps. Expression, activation, inhibition, binding, and reaction were considered in action plan. Results: Numbers of 16 proteins were recognized by STRING database and were included in the network. Except PHRF1, the other 15 query proteins were included in the main connected component of the constructed network. Ten central nodes of the network and ten numbers of top query proteins based on degree value were identified as central proteins of the network. All nodes of the network analyzed via action maps and the important acted nodes were determined as RPSA, GAPDH, TPT1, DCTN2, HSPB1, and PDIA3. Conclusion: Two balanced processes including cancer promotion and cancer prevention were after irradiation were identified., (Copyright © 2019 J Lasers Med Sci.)

Introduction: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes which can cause vision loss or blindness ultimately. Non enzymatic glycation of proteins leads to advanced glycation end products (AGEs) in DR. Since laser therapy is a well-established method, in this study, protein-protein interaction (PPI) network is applied for protein targets in DR disease in rats treated by laser. Methods: In this study, we focused on articles that investigated and compared the proteome profiles of DR rats with healthy control and also DR rats before and after laser therapy. The networks of related differentially expressed proteins were explored using Cytoscape version 3.3.0, the PPI analysis methods and ClueGO. Results: Analysis of PPI network of 37 related proteins to DR rats including 108 nodes, introduced 10 hub-bottleneck proteins and 5 concerned biochemical pathways. On the other hand, PPI analysis of related proteins to DR rats before and after laser therapy corresponded to 33 proteins and 2 biological pathways. Discussion: Centrality and cluster screening identified hub-bottelneck genes, including Aldoa, HSPD1, Pgam2, Mapk3, SLC2A4, Ctnnb1, Ywhab, HSPA8, GAPDH and Actb for DR rats versus healthy control and ENO1, Aldoa, GAPDH for DR samples after laser therapy., Conclusion: Gene expression analysis of the DR samples treated via laser therapy provides a molecular evidence in support of the therapeutic effect of laser.

Introduction: Periodontitis is a set of inflammatory disorders characterized by periodontal attachment loss and alveolar bone resorption. Because of deficiency in periodontitis mechanical therapy, this study was aimed to explore the molecular influence of the erbiumdoped: yttrium aluminum garnet (Er:YAG) laser and cyclosporin A (CsA) on human gingival fibroblasts (HGFs) for improvement in periodontal diseases therapy. Methods: We focused on articles that studied the proteome profiles of HGFs after treatment with laser irradiation and application of CsA. The topological features of differentially expressed proteins were analyzed using Cytoscape Version 3.4.0 followed by module selection from the protein-protein interaction (PPI) network using Cluster ONE plugin. In addition, we performed gene ontology (GO) enrichment analysis for the densely connected region and key proteins in both PPI networks. Results: Analysis of PPI network of Er:YAG laser irradiation on HGFs lead to introducing YWHAZ, VCP, HNRNPU, YWHAE, UBA52, CLTC, FUS and IGHG1 as key proteins while similar analysis revealed that ACAT1, CTSD, ALDOA, ANXA2, PRDX1, LGALS3, ARHGDI and EEF1A1 are the crucial proteins related to the effect of drug. GO enrichment analysis of hubbottleneck proteins of the 2 networks showed the different significant biological processes and cellular components. The functional enrichments of module of Er:YAG laser network are included as fatty acid transmembrane transport, cytokinesis, regulation of RNA splicing and asymmetric protein localization. There are not any significant clusters in network of HGF treated by CsA. Conclusion: The results indicate that there are 2 separate biomarker panels for the 2 treatment methods.