Introducing critical proteins related to liver ischemia/reperfusion injury.

Aim: The current study aimed to introduce the key proteins involved in liver ischemia/reperfusion (I/R) injury through protein-protein interaction (PPI) analysis. Background: Liver transplantation (LT) is a well-known treatment for liver diseases that threaten patients with mortality. LT is a complex operation, and several risks, including liver I/R injury, affect its success. Improving LT requires detection of its molecular mechanism. Experiments have revealed that high throughput methods such as proteomics in combination with bioinformatics are useful tools for analyzing the molecular mechanism of disease. Methods: The differentially expressed proteins (DEPs) involved in liver I/R injury were extracted from the literature. The queried DEPs plus the first 100 neighbors were included in a network through STRING database using Cytoscape software. Degree, betweenness centrality, closeness centrality, and stress were considered to determine the central nodes. The queried DEPs were assessed by action map analysis using the CluePedia application of Cytoscape software. The key proteins were identified by comparing network analysis and action map evaluation results. Results: Six proteins, namely ALB, INS, GAPDH, CAT, IL6, and TNF, among the added first neighbors were determined as the central first neighbors. MPO, CRP, MMP9, and HMOX1 were selected as central DEPs among the queried proteins. Action map analysis confirmed the PPI findings. The final evaluation revealed that MMP9 in combination with CRP and HMOX1 plays a critical role in liver I/R injury. Conclusion: The significant role of MMP9 in liver I/R injury was detected in this study. Two central proteins (CRP and HMOX1) were shown to have a regulatory effect on MMP9; CRP activated MMP9, while HMXO1 downregulated it.

The connection between fatty acids and inflammation in celiac disease; a deep exploring.

The interplay between fatty acids (FAs) and celiac disease (CD) is a burgeoning field of research with significant implications for understanding the pathophysiology and potential therapeutic avenues for this autoimmune disorder. CD, triggered by gluten consumption in susceptible individuals, presents with a range of intestinal and extra-intestinal symptoms impacting various bodily functions. The disruption of intestinal tight junctions (TJs) by gluten proteins leads to increased gut permeability and subsequent inflammatory responses mediated by T-cells. FAs, crucial components of cell membranes, play diverse roles in inflammation and immune regulation. In fact, FAs have been shown to modulate inflammatory processes through various mechanisms. Studies have highlighted alterations in FA profiles in individuals with CD, indicating potential implications for disease pathogenesis and micronutrient deficiencies. Moreover, the exploration of FAs as biomarkers for CD diagnosis offers promising avenues for future research and therapeutic interventions. Understanding the intricate relationship between FAs and CD could lead to novel approaches in managing this complex autoimmune disorder. Therefore, this review article aims to provide an overview of the connection between FAs and inflammation in CD.

Intestinal mRNA expression analysis of polarity-related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease.

BACKGROUND: Celiac disease (CD) is a chronic autoimmune disorder characterized by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. It is well established that the integrity of epithelial tight junctions (TJs) and adherens junctions (AJs) plays a crucial role in the pathogenesis of CD. These junctional complexes contribute to the apical-basal polarity of the intestinal epithelial cells, which is crucial for their proper functioning. METHODS: Sixty CD subjects, and 50 controls were enrolled in the current study. Mucosal samples were obtained from the distal duodenum, total RNA was extracted and complementary DNA was synthesized. The relative expression levels of the desired genes were evaluated by quantitative real-time polymerase chain reaction based on ΔΔCt method. The gene-gene interaction network was also constructed using GeneMANIA. RESULTS: CRB3 (p = .0005), LKB1 (p < .0001), and SCRIB (p = .0005) had lower expression in CD patients compared to controls, while PRKCZ expression did not differ between groups (p > .05). CRB3 represented a significant diagnostic value for differentiating CD patients from the control group (p = .02). CONCLUSION: The aim of the current study was to evaluate the changes in the mRNA expression levels of SCRIB, PRKCZ, LKB1, and CRB3 genes in the small intestinal biopsy samples of CD patients in comparison to the healthy control subjects. Our data uncover the importance of polarity-related genes (especially CRB3) in CD pahtomechanism, that may facilitate the planning of the future studies looking for finding innovative diagnostic and therapeutic strategies for CD.

Standardized GMP-Compliant Scalable 3D-Bioprocessing of Epidermal Stem Cells for Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) pose a significant threat to the health and well-being of individuals with diabetes, often leading to lower limb amputations. Fortunately, epidermal stem cell therapy offers hope for improving the treatment of DFUs. By leveraging 3D culture techniques, the scalability of stem cell manufacturing can be greatly enhanced. In particular, using bioactive materials and scaffolds can promote the healing potential of cells, enhance their proliferation, and facilitate their survival. Furthermore, 3D tissue-mimicking cultures can accurately replicate the complex interactions between cells and extracellular matrix, thereby ensuring that the stem cells are primed for therapeutic application. To ensure the safety and quality of these stem cells, it is essential to adhere to good manufacturing practice (GMP) principles during cultivation. This chapter provides a comprehensive overview of the step-by-step process for GMP-based 3D epidermal stem cell cultivation, thus laying the groundwork for developing reliable regenerative medicine therapies.

Metabolomics and lipidomics signature in celiac disease: a narrative review.

Celiac disease (CD) is a chronic immune-mediated inflammatory disease of the small intestine caused by aberrant immune responses to consumed gluten proteins. CD is diagnosed by a combination of the patients reported symptoms, serologic and endoscopic biopsy evaluation of the small intestine; and adherence to a strict gluten-free diet (GFD) is considered the only available therapeutic approach for this disorder. Novel approaches need to be considered for finding new biomarkers to help this disorder diagnosis and finding a new alternative therapeutic method for this group of patients. Metabolomics and lipidomics are powerful tools to provide highly accurate and sensitive biomarkers. Previous studies indicated a metabolic fingerprint for CD deriving from alterations in gut microflora or intestinal permeability, malabsorption, and energy metabolism. Moreover, since CD is characterized by increased intestinal permeability and due to the importance of membrane lipid components in controlling barrier integrity, conducting lipidomics studies in this disorder is of great importance. In the current study, we tried to provide a critical overview of metabolomic and lipidomic changes in CD.

Isolation and Phenotypic Characterization of Tumor-Infiltrating NK Cells in Skin Carcinoma.

In oncological research, the function of tumor-infiltrating natural killer (NK) cells in skin carcinoma presents a viable avenue for novel therapeutic methods. NK cells are essential to the body's defense against malignancies, including skin cancer, and are especially important in more sophisticated cancer immunotherapies such as vaccinations containing dendritic cells. The deadliest type of skin cancer, malignant melanoma, still has a poor prognosis even with advancements in early-stage therapies, which emphasizes the need for novel therapeutic strategies. NK cells from human melanoma metastases were subjected to single-cell RNA-seq analysis, which demonstrated notable variations in the transcriptional programs of tumor-infiltrating and circulating NK cells. Different transcriptional states are displayed by NK cells that have invaded tumors, indicating that they are functionally specialized in areas like chemokine production and cytotoxicity. These results emphasize the functions of NK cells in recruiting other significant immune cell types, such as cross-presenting dendritic cells, and in direct cytotoxicity against malignant cells. Investigating NK cells that infiltrate tumors in skin carcinomas presents a viable approach to comprehending and may be modifying the immune environment surrounding these cancers. It is essential to comprehend the distinct characteristics and roles of NK cells inside the tumor microenvironment in order to create more potent immunotherapeutic approaches to treat skin cancer. In order to perhaps open the door for new directions in cancer immunotherapy, the project intends to establish a thorough technique for the isolation and thorough phenotypic characterization of tumor-infiltrating NK cells in skin carcinoma.

Acellular Fish Skin for Deep Dermal Traumatic Wounds Management; Introducing a Novel Dressing.

The optimal therapy for deep wounds is based on the early debridement of necrotic tissue followed by wound coverage to avoid a systemic inflammatory response and optimize scar-free healing. The outcomes are affected by available resources and underlying patient factors, which cause challenges in wound care and suboptimal outcomes. Here we report a patient with deep dermal injury wounds, who was treated with platelet-rich fibrin (PRF) gel, plasma rich in growth factor (PRGF) gel, and acellular fish skin. Patient's outcomes regarding healing and scar quality were collected objectively and subjectively for one year after the injury. Wounds treated with acellular fish skin demonstrated accelerated wound healing, a significantly higher water-storage capacity, and better pain relief. Furthermore, improved functional and cosmetic outcomes, such as elasticity, skin thickness, and pigmentation, were demonstrated. It seems that, the PRGF gel and PRF in combination with acellular fish skin grafts resulted in the faster healing of wounds and better functional and aesthetic outcomes than split-thickness skin grafts treatment.

Evaluating CD4 and Foxp3 mRNA Expression in Tissue Specimens of Celiac Disease and Colorectal Cancer Patients.

OBJECTIVE: Celiac disease (CD) and colorectal cancer (CRC) are distinct gastrointestinal conditions with a debated association. This study aimed to evaluate the mRNA expression of CD4 and Foxp3 in tissue specimens of CD and CRC patients. The findings can provide valuable insights into the complex connection between these different gastrointestinal conditions. METHODS: Tissue samples from 100 CRC patients, 50 CD patients, and 50 healthy controls (HCs) were collected. RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed. Statistical analysis was conducted using ANOVA and Pearson's correlation test. RESULT: CD4 mRNA expression was significantly higher in CRC patients compared to CD patients and HCs (P<0.0001 for both). Foxp3 mRNA expression was significantly higher in CD patients compared to CRC patients and HCs (P<0.0001 for both). Clinicopathological characteristics did not correlate significantly with gene expression levels. CONCLUSION: This study reveals differential expression patterns of CD4 and Foxp3 mRNA in CRC and CD patients. Upregulated CD4 mRNA suggests its potential role in promoting tumor growth, while increased Foxp3 mRNA expression may reflect an immunosuppressive mechanism in CD pathogenesis. These findings provide insights into the molecular and immunological aspects of CRC and CD, warranting further studies for potential therapeutic strategies.

Classification and Diagnostic Prediction of Colorectal Cancer Mortality Based on Machine Learning Algorithms: A Multicenter National Study.

INTRODUCTION: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths. This study aimed to predict survival outcomes of CRC patients using machine learning (ML) methods. MATERIAL AND METHODS: A retrospective analysis included 1853 CRC patients admitted to three prominent tertiary hospitals in Iran from October 2006 to July 2019. Six ML methods, namely logistic regression (LR), Naïve Bayes (NB), Support Vector Machine (SVM), Neural Network (NN), Decision Tree (DT), and Light Gradient Boosting Machine (LGBM), were developed with 10-fold cross-validation. Feature selection employed the Random Forest method based on mean decrease GINI criteria. Model performance was assessed using Area Under the Curve (AUC). RESULTS: Time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type emerged as crucial predictors of survival based on mean decrease GINI. The NB (AUC = 0.70, 95% Confidence Interval [CI] 0.65-0.75) and LGBM (AUC = 0.70, 95% CI 0.65-0.75) models achieved the highest predictive AUC values for CRC patient survival. CONCLUSIONS: This study highlights the significance of variables including time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type in predicting CRC survival. The NB model exhibited optimal efficacy in mortality prediction, maintaining a balanced sensitivity and specificity. Policy recommendations encompass early diagnosis and treatment initiation for CRC patients, improved data collection through digital health records and standardized protocols, support for predictive analytics integration in clinical decisions, and the inclusion of identified prognostic variables in treatment guidelines to enhance patient outcomes.

Overview of the compromised mucosal integrity in celiac disease.

Intestinal epithelium is a dynamic cellular layer that lines the small-bowel and makes a relatively impenetrable barrier to macromolecules. Intestinal epithelial cell polarity is crucial in coordinating signalling pathways within cells and mainly regulated by three conserved polarity protein complexes, the Crumbs (Crb) complex, partitioning defective (PAR) complex, and Scribble (Scrib) complex. Polarity proteins regulate the proper establishment of the intercellular junctional complexes including tight junctions (TJs), adherence junctions (AJs), and desmosomes which hold epithelial cells together and play a major role in maintaining intestinal barrier integrity. Impaired intestinal epithelial cell polarity and barrier integrity result in irreversible immune responses, the host- microbial imbalance and intestinal inflammatory disorders. Disassembling the epithelial tight junction and augmented paracellular permeability is a conspicuous hallmark of celiac disease (CD) pathogenesis. There are several dietary components that can improve intestinal integrity and function. The aim of this review article is to summarize current information about the association of polarity proteins and AJC damages with pathogenesis of CD.

Human-Induced Pluripotent Stem Cell‒Derived Keratinocytes, as Therapeutic Option in Vitiligo.

Vitiligo is a skin condition affecting 1% of the global population, causing non-scaly, chalky-white macules on the skin and hair. It is caused by the pathologic destruction of melanocytes, which produce melanin. Research has focused on the abnormalities of melanocytes and their interaction with neighboring keratinocytes. Current treatments are mainly immunosuppressive drugs and UV radiation, which are scarce and ineffective. To treat vitiligo, regenerative medicine techniques, such as cell-based and cell-free methods, are recommended. Keratinocyte cell transplantation has shown promising results in treating vitiligo. Moreover, studies suggest individualized therapy for diseases can be provided by reprogramming somatic cells into induced pluripotent stem cells. On the other hand, differentiation into particular cell types is a key component of induced pluripotent stem cells-based treatment. In this chapter, the differentiation and validation of human induced pluripotent stem cells into a keratinocyte as a therapeutic option in vitiligo will be discussed.

Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study.

Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents.

Botulinium toxin applications in the lower face and neck: A comprehensive review.

BACKGROUND: Botulinum toxin has been widely and mainly used for the treatment of conditions affecting the upper and middle face; however, recent efforts have expanded the indications of botulinum toxin injection to the lower face and neck areas for cosmetic and medical purposes. AIMS: We have reviewed the latest updates on using botulinum toxin in the lower face and neck focusing on cosmetic purposes and have discussed the existing concerns as well as the adverse sequelae of these newer indications. PATIENTS/METHODS: A comprehensive literature search was performed using the following keywords [[botulinum] AND [[Toxin] OR [Neurotoxin]]] AND [[Lower AND Face] AND/OR [Neck]] within the main databases including Web of Science, PubMed, Embase and gray literature on and before February 2023. The data were screened using titles and abstracts and those relevant to the topic were included in the paper. RESULTS: Botulinum toxin injection has considerable cosmetic and therapeutic effect on facial contouring, masseteric hypertrophy, lower face and neck scars, gummy smile, drooping lip corner and even skin rejuvenation. CONCLUSION: BNT injection has been widely used for the treatment of different medical and cosmetic purposes. Low rates of side effects, which were self-limited in most cases, have been reported in the literature, making BNT a safe therapeutic medication in most cases. However, regulatory status needs to be updated and more accurately revised in many countries and more comprehensive research is required to address the existing gaps in this area including the site, dosage, and method of injection in each case.

Comparison of the effects of preservation methods on structural, biological, and mechanical properties of the human amniotic membrane for medical applications.

Amniotic membrane (AM), the innermost layer of the placenta, is an exceptionally effective biomaterial with divers applications in clinical medicine. It possesses various biological functions, including scar reduction, anti-inflammatory properties, support for epithelialization, as well as anti-microbial, anti-fibrotic and angio-modulatory effects. Furthermore, its abundant availability, cost-effectiveness, and ethical acceptability make it a compelling biomaterial in the field of medicine. Given the potential unavailability of fresh tissue when needed, the preservation of AM is crucial to ensure a readily accessible and continuous supply for clinical use. However, preserving the properties of AM presents a significant challenge. Therefore, the establishment of standardized protocols for the collection and preservation of AM is vital to ensure optimal tissue quality and enhance patient safety. Various preservation methods, such as cryopreservation, lyophilization, and air-drying, have been employed over the years. However, identifying a preservation method that effectively safeguards AM properties remains an ongoing endeavor. This article aims to review and discuss different sterilization and preservation procedures for AM, as well as their impacts on its histological, physical, and biochemical characteristics.

Development of CAR-NK Cells Targeting cSCC-Specific Antigens for Precision Immunotherapy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer that is frequently diagnosed, is distinguished by its propensity for aggressive behavior, frequent poor response to standard therapy, and capacity to metastasize to distant areas. Utilizing the body's natural immune defense mechanisms, particularly through the use of chimeric antigen receptor (CAR) technology, is receiving increasing attention in the dynamic field of oncological therapies. Although T cells have received most of the attention, this strategy has proven to be highly effective in battling some blood-related malignancies. However, there are considerable challenges when using this method in the context of solid tumors. The innate immune system's natural killer (NK) cells are essential parts because they have the ability to detect and destroy cancer cells. CAR-NK cells are a very promising approach because they combine the natural cytotoxic properties of natural killer (NK) cells with the precise targeting skills of chimeric antigen receptor (CAR) technology. With the use of this integrated strategy, the intrinsic diversity of cutaneous squamous cell carcinoma (cSCC) tumors may be successfully targeted, increasing treatment effectiveness and lowering the risk of tumor recurrence. This tactic is improved by the development of dual-specificity chimeric antigen receptors (CARs), which fully resolve the antigen presentation heterogeneity among tumor cells. In conclusion, the use of CAR-NK cells that precisely target cSCC-specific antigens has the potential to drastically transform therapy approaches for cSCC as well as other difficult solid tumors as oncological research advances. In order to create chimeric antigen receptor (CAR)-natural killer (NK) cells that particularly target antigens linked to cutaneous squamous cell carcinoma (cSCC), the goal of this protocol is to present a detailed method. The ultimate objective is to lay the groundwork for the development of precision immunotherapy.

Laser Diode - GaAlAs Acupuncture in the Treatment of Central Obesity: a Randomized Clinical Trial.

Background: : Obesity is a global health challenge. Traditional approaches, including increased physical activity, dietary interventions, and medical therapy, often yield limited success, propelling some patients toward costly and invasive procedures like bariatric surgery. Laser acupuncture has been suggested as a complementary therapeutic approach to overcome this challenge. The present study investigated the effectiveness of laser acupuncture treatment in weight loss and abdominal subcutaneous fat reduction. Methods: : A randomized, blinded, sham-controlled clinical trial was conducted, with 30 subjects each in the intervention and control groups. Patients in the intervention group underwent 12 sessions of laser acupuncture treatment within a month (three sessions/week), whereas those in the control group received sham laser treatment on identical acupoints. The patients were instructed not to alter their physical activity levels or dietary regimens. All parameters were evaluated before and after the treatment. Results: : Significant reductions in weight, body mass index, and waist circumference were noted in both intervention and control groups. Further analysis revealed a more significant decrease in the laser acupuncture group. Abdominal sonography revealed a marked decrease in periumbilical fat thickness in the intervention group. Conversely, laboratory evaluations showed no significant difference between the two groups. Conclusion: : Laser acupuncture is an effective method for weight loss in patients with periumbilical abdominal fat. The observed impact on subcutaneous fat suggests its potential as a non-invasive intervention for individuals seeking weight management alternatives. Further research is warranted to validate these findings and explore the underlying mechanisms of laser acupuncture in adipose tissue modulation.

Assessment of the Response of Human Umbilical Vein Endothelial Cells to Photodynamic Therapy: Highlighting the Role of Il-17 Signaling Pathway.

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.

Efficacy Evaluation of Human Skin Treatment with Photodynamic Therapy in Actinic Keratoses Patients.

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.

Evaluation of the Cellular Resistance Process in Treated Cells Via Extracorporeal Photopheresis.

Introduction: Extracorporeal photopheresis (ECP) is a therapeutic method applied against some diseases such as cancers. Using 8-methoxypsoralen (8-MOP) and UVA radiation in ECP is associated with achievement in the treatment of patients with leukemic cutaneous T-cell lymphoma (CTCL). Evaluation of cellular resistance versus ECP is the aim of this study. Methods: Data were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed via the GEO2R program. The significant DEGs were assessed via protein-protein interaction (PPI) network analysis by using the STRING database and Cytoscape software. The critical genes were evaluated via gene ontology by using the ClueGO application of Cytoscape software. The identified biological processes were determined and analyzed. Results: Fifty-seven significant DEGs were determined. The main connected component of the PPI network including 32 queried significant DEGs plus 50 first neighbors was constructed. Nineteen histones as critical nodes were assessed via gene ontology, and "nucleosome organization" was pointed out as the crucial biological process. Finally, 15 histones from H2A, H2B, and H3 histone families were identified as the key genes that are involved in the resistance property of the treated cells. Conclusion: In conclusion, 15 members of H2A, H2B, and H3 families (especially H2A family) were considered as the origin of resistance versus ECP treatment. It is concluded that sensitivity to ECP treatment depends on gross molecular events which are involved in the functions of histones.

Assessment of Photosensitizer Concentration Effects on the Efficacy of Photodynamic Therapy.

Introduction: Photodynamic therapy (PDT) is an attractive approach in medicine. Due to its noninvasive nature and low side effects, PDT has been developed quickly. In the present study, the gene expression profiles of the human cell line that was treated via PDT in the sub-lethal concentration (LC50) and super-lethal concentration (LC90) of a photosensitizer (PS) from Gene Expression Omnibus (GEO) were extracted and the common differentially expressed genes (DEGs) were investigated. Methods: The gene expression profiles of the treated cells were compared with a control, and the common DEGs were determined. The common DEGs were assessed via protein-protein interaction (PPI) network analysis, and gene ontology enrichment was evaluated. The related biological terms for the common genes were identified. Results: Ninety-four common DEGs were selected to be analyzed. It appeared that the activation and increment of gene expression were prominent processes. Jun, Dusp1, Atf4, and Atf3 as four critical genes were highlighted. "Chromosomal and microsatellite instability in colorectal cancer" was identified as the main class of biological terms related to the assessed DEGs. Conclusion: The major molecular events which happened in both analyses indicated that PDT, independent from the concentration of PS, induced gross molecular changes such as the upregulation of Jun and Dusp1.