Histopathologic Changes of Appendicitis Stage During the COVID-19 Pandemic.

Background: We decided to compare the pathology stage of appendicitis in patients referred to Firoozabadi Medical Center before and after the official announcement of the coronavirus outbreak in Iran because we believe that people's fears of COVID-19 are keeping them away from hospitals and it likely causes them to come in later stages of the disease. Therefore, this study aims at investigating the effect of the COVID-19 pandemic on the stage of appendicitis at presentation. Methods: In this retrospective study, histopathology records of all acute appendicitis patients who underwent an emergency appendectomy in the surgical unit in our institute between December 2019 and April 2020 were reviewed retrospectively. The study period was designed to include 2 months before and 2 months after the officially announced onset of the COVID-19 outbreak in Iran on February 20, 2020. All cases of complicated appendicitis (perforated appendicitis, phlegmonous appendix, itis or abscess) were excluded. Descriptive statistics were used to describe our study variables. Furthermore, ordinal logistic regression was used to investigate the effect of the COVID-19 pandemic and demographic variables on the stage of appendicitis at presentation. Data were analyzed using SPSS Statistics Version 22. Results: The study was conducted on 170 clinically diagnosed acute appendicitis patients. The odds ratio for gender was equal to 0.45 (0.23, 0.86), which means that women presented at an earlier pathological stage than men ( p = 0.016). Also, patients who had health insurance were 50% less likely to present in later pathological stages than those who did not ( p = 0.024). The COVID-19 outback did not have a significant role in the pathological stage at presentation ( p = 0.235). Conclusion: The number of appendicitis patients was down by about 50% following the outbreak announcement in Iran. Surprisingly, we did not find any significant changes in the distribution pattern of appendicitis pathological staging after the outbreak. Being uninsured and male sex were found to have the most significant roles in delayed hospital presentation and higher pathological stages in patients with acute appendicitis.

Inflammation and immunological disarrays are associated with acute exercise in type 2 diabetes.

Objective: Type 2 diabetes (T2D) is the most common metabolic disorder that is associated with insulin resistance. The aim of the present study is to discover details of the molecular mechanism of exercise on control or progress of diabetic condition in patients via network analysis. Methods: Gene expression profiles of patients with T2D before and after doing exercise are retrieved from Gene Expression Omnibus (GEO) and are pre-evaluated by the GEO2R program. Data are studied based on expression values, regulatory relationships between the differentially expressed genes (DEGs), gene ontology analyses, and protein-protein interaction PPI network analysis. Results: A number of 118 significant DEGs were identified and classified based on fold change (FC) values as most dysregulated genes and dysregulated individuals. Action map analysis revealed that 18 DEGs appeared as the critical genes. Gene ontology analysis showed that 24 DEGs are connected to at least four pathways. JUN, IL6, IL1B, PTGS2, FOS, MYC, ATF3, CXCL8, EGR1, EGR2, NR4A1, PLK3, TTN, and UCP3 were identified as central DEGs. Conclusion: Finally; JUN, IL6, IL1B, PTGS2, FOS, ATF3, CXCL8, EGR1, and EGR2 were introduced as the critical targeted genes by exercise. Since the critical genes after exercise are upregulated and mostly are known as the risk factors of T2D, it can be concluded that unsuitable exercise can develop diabetic conditions in patients. Acute exercise-induced inflammation and immune disturbances seem to be associated with the development of T2D in patients.

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.

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 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.

Introducing critical common dysregulated proteins in esophageal, gastric, and intestinal cancers.

Aim: The current study aimed to determine the common dysregulated proteins between esophageal, gastric, and intestinal cancers. Background: Though there are several documents about the role of AKT1 in promoting of esophageal, gastric, and intestinal cancers, there is not enough evidence about the dominant role of AKT1 relative to the other oncogene genes in the promotion of the three studied cancer types. Methods: One hundred proteins related to each of esophageal, gastric, or intestinal cancer were retrieved from the STRING database and interacted by Cytoscape software v 3.2.7. 2 to create the correlated interactomes. The network was analyzed by the "NetworkAnalyzer" application of Cytoscape to find the centrality parameters of the nodes. Results of network analysis and action map assessment were used to determine the common critical proteins between the three studied cancers. Results: One hundred proteins were extracted for each of the studied cancers. Among 42 common dysregulated proteins, 36 individuals were selected through network analysis and were screened through action map assessment. Eighteen proteins were introduced as the important common proteins. Finally, AKT1 was a candidate for the crucial dysregulated proteins common in the three analyzed diseases. Conclusion: The findings indicate that AKT1, relative to the other oncogene genes, is a suitable candidate to be evaluated in patients as a prediagnostic tool to reduce endoscopy and colonoscopy rates.

Evaluation of Positive Predictors of Micrometastasis in Central Lymph Nodes in Patients with Papillary Thyroid Cancer; A Cross-Sectional Study.

Background & Objective: Papillary thyroid cancer (PTC) is the most common primary cancer originating from thyroid follicular cells. The aim of this study was to evaluate the positive predictors of micrometastasis in central lymph nodes in patients with papillary thyroid cancer. Methods: This was a cross-sectional study. The study population was all known PTC patients who underwent total thyroidectomy and lymph node dissection of the central neck nodes based on the current indications. Confirmation of central lymph node involvement was performed by permanent smear after surgery. Data were analyzed using SPSS software version 22. A P-value below 0.05 was considered statistically significant. Results: There was no significant relationship between age, gender, family history of PTC, family history of thyroid disease, multinodularity, history of other thyroid diseases, involvement of two thyroid lobes, and tumor grade with central lymph node involvement (P>0.05). There was a significant relationship between the tumor pathology and size with central lymph node involvement (P<0.05). Moreover, logistic multivariate regression analysis showed that female gender, multinodularity, and tumor size had a significant relationship with the incidence of central lymph node involvement (P<0.05). Conclusion: Female gender, multinodularity, and larger tumor size may be predictors of micrometastasis in central lymph nodes in patients with papillary thyroid cancer.

Network Analysis of Effect of Light-Dark Time Ratio on the Gene Expression Profile of Mouse Skin.

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.

Introducing BDNF and SNAI1 as the Crucial Targeted Genes by UV Radiation.

Introduction: Due to widespread penetration of UV radiation in human life, the biological effect of UV radiation is studied through many investigations in the field of medicine. There are many assessments about UV radiation which are concerned with protein-protein interaction (PPI) network analysis. In the present study, a network analysis associated with the complementary evaluation of UV radiation on human primary melanocytes is presented. Methods: The gene expression profiles of the irradiated human primary melanocytes and the control cells were extracted from Gene Expression Omnibus (GEO) and were evaluated via PPI network analysis and action map assessment. Results: 69 significant differentially expressed genes (DEGs) were included in the main component of the PPI network. Brain-derived neurotrophic factor (BDNF), SNAI1, and SOCS1 were highlighted as the top dysregulated and hub genes. Results indicate that BDNF and SNAI1 participate in the regulatory unit including the total hubs and top dysregulated genes. Conclusion: Considerable down-regulation of BDNF and up-regulation of SNAI1 as the two critical targeted genes by UV radiation are accompanied by gross alteration in cell functions.

Obsessive-Compulsive Disorder Interactome Profile Analysis: A Perspective From Molecular Mechanism.

INTRODUCTION: Obsessive-Compulsive Disorder (OCD) is one of the complex neuropsychiatric conditions. This disorder disables individuals in many different aspects of their personal and social life. Interactome analysis may provide a better understanding of this disorder's molecular origin and its underlying mechanisms. METHODS: In this study, the OCD-associated genes were extracted from the literature. The criterion for gene selection was to choose genes with at least one significant report. Furthermore, by applying Cytoscape and its plugins, protein-protein interaction network, and gene ontology of the 31 candidate genes related to OCD from genetic association studies is examined. The cross-validation method was used for network centrality assessment. RESULTS: A scale-free network, including 1940 nodes and 3269 edges for 31 genes, was constructed. According to the network centrality evaluation, ESR1, TNFα, DRD2, DRD4, HTR1B, HTR2A, and CDH2 showed the highest values and can be considered hub-bottlenecks elements. It is also confirmed by the number of 123 cross-validation tests that the frequency of these essential genes remains unaltered against the initial seed genes' changes with the accuracy of 0.962. Besides, enrichment analysis identified four highlighted biological processes related to the 31 candidate genes. The top biological processes are determined as dopamine transport, learning, memory, and monoamine transport. CONCLUSION: Among 31 initial genes, 7 were introduced as crucial elements for onset and development in OCD and can be suggested for further investigations. Furthermore, the complex molecular origin of OCD requires high-throughput screening for diagnosis and treatment goals. The findings are a possible valuable source to establish molecular-based diagnostic tools for OCD.

Bioinformatics Investigation and Contribution of Other Chromosomes Besides Chromosome 21 in the Risk of Down Syndrome Development.

INTRODUCTION: Down syndrome as a genetic disorder is a popular research topic in molecular studies. One way to study Down syndrome is via bioinformatics. METHODS: In this study, a gene expression profile from a microarray study was selected for more investigation. RESULTS: The study of Down syndrome patients shows specific genes with differential expression and network centrality properties. These genes are introduced as RHOA, FGF2, FYN, and CD44, and their level of expression is high in these patients. CONCLUSION: This study suggests that besides chromosomes 21, there are additional contributing chromosomes to the risk of Down syndrome development. Besides, these genes could be used for clinical studies after more analysis.

C-reactive protein as a possible marker for severity and mortality of COVID-19 infection.

AIM: The present study aimed to introduce a possible biomarker to differentiate between severe and fatal conditions of COVID-19. BACKGROUND: The COVID-19 pandemic, appearing as a complicated health problem, has changed the lifestyle of people in recent years. Clinical findings indicate mild, severe, and fatal conditions of this disease. Prediction of disease severity is a significant point in managing COVID-19 infection. METHODS: In this study, 195 differentially expressed genes (DEGs) that discriminate between fatal and severe conditions in patients were extracted from the literature and screened to determine the significant ones. The significant DEGs plus the 90 first neighbors added from the STRING database were included in the interactome using Cytoscape software v 3.7.2. The central nodes of the analyzed network were identified and assessed. RESULTS: Ten significant DEGs were candidates for assessment, of which 9 were recognized by the STRING database. IL6, ALB, TNF, CRP, INS, MPO, C3, CXCL8, TTR, and TLR4 were determined as central nodes; IL6, CRP, and TTR were highlighted as the critical genes related to the severity of COVID-19 infection. CONCLUSION: CRP was identified as the best possible biomarker with levels related to the severity and fatality of COVID-19 infection.

Low-Level Laser Therapy Effects on Rat Blood Hemostasis Via Significant Alteration in Fibrinogen and Plasminogen Expression Level.

Introduction: There are many documents about the significant role of low-level laser therapy (LLLT) in different processes such as regenerator medicine and bone formation. The aim of this study is to assess the role of LLLT in blood hemostasis in rats via bioinformatic investigation. Methods: The differentially expressed plasma proteins of treated rats via LLLT from the literature and the added 50 first neighbors were investigated via network analysis to find the critical dysregulated proteins and biological processes by using Cytoscape software, the STRING database, and ClueGO. Results: A scale-free network including 55 nodes was constructed from queried and added first neighbor proteins. Fibrinogen gamma, fibrinogen alpha, and plasminogen were highlighted as the central genes of the analyzed network. Fibrinolysis was determined as the main group of biological processes that were affected by LLLT. Conclusion: Findings indicate that LLLT affects blood hemostasis which is an important point in approving the therapeutic application of LLLT and also in preventing its possible complication.

Effect of UV Laser Radiation on "Positive Regulation of Telomere Maintenance" in Saccharomyces cerevisiae.

Introduction: Excessive exposure to ultraviolet (UV) radiation may cause a variety of skin cancers and damage to the eye lens. The assessment of different aspects of UV damage has attracted researchers' interest. UV radiation to simple biological models such as Saccharomyces cerevisiae of yeast family could help to find out different molecular changes resulting from radiation. The assessment and network analysis of gene expression data about yeast cells radiated by the UV laser was the aim of this study. Methods: The gene expression profiles of S. cerevisiae samples in the presence of the UV laser at 30 seconds radiation and 15 minutes' post-radiation time are compared with the control profiles. The significant expressed genes interacted and the central nodes and related biological terms were identified. Results: The main connected component of the network including 427 nodes was analyzed and 11 central differentially expressed genes (DEGs) were determined. RPN11, UBI4, HSP82, and HSC82 as critical DEGs and "positive regulation of telomere maintenance" as a related biological term were introduced. Conclusion: The finding has provided a new perspective on laser application in the rejuvenation process. It seems that the laser can be used as a suitable agent against the aging process which is a limiting factor in human life.

Assessment of Post-Radiation Time Effect on Gene Expression Profiles of Saccharomyces cerevisiae Samples After Appling a UV Laser.

Introduction: Widespread application of lasers in different fields of medicine implies more investigations into the molecular mechanism of laser effects on the human body. Network analysis of the dysregulated genes of Saccharomyces cerevisiae samples are irradiated by a UV laser and harvested 30 minutes after radiation compared with a 15-minute group is the aim of this research. Methods: The significant dysregulated genes interacted via the STRING database, and the central nodes were determined by "Networkanalyzer" application of Cytoscape software. The critical genes and the related biological terms were identified via action map analysis and gene ontology assessment. Results: The gene expression profiles of the samples with 30-minute post-radiation time were different from the samples with 15 minutes of post-radiation time. 9 potent central genes, 50% of which were similar to the nodes of the 15-minute group, were identified. The terms "positive regulation of telomere maintenance" were targeted in the two sample groups. Conclusion: In spite of large alteration in the gene expression profiles of the samples, the results indicated that the main affected biological term for the 15-minute and 30-minute groups was similar.

Investigating the Effects of Ibuprofen on the Gene Expression Profile in Hippocampus of Mice Model of Alzheimer's Disease through Bioinformatics Analysis.

Non-steroidal anti-inflammatory drugs (NSAIDs) are identified as effective in many diseases. One of which is neurodegenerative diseases including Alzheimer disease (AD). In this study gross alteration of gene expression in AD mice by ibuprofen treatment is investigated via Protein-protein interaction network (PPI) analysis. Expression profiling of microarray dataset GSE67306 was retrieved from GEO database and analyzed via GEO2R tool. PPI analysis was performed via Cytoscape 3.7.0. and its plug-ins including Network Analyzer, Gene MANIA, and CluePedia. Numbers of 10 central genes including Htr1a, Sstr2, Drd2, Htr1b, Penk, Pomc, Oprm1, Npy, Sst, and Chrm2 were identified as potential biomarkers. However, the role of Penk gene was highlighted. The finding indicates that ibuprofen changes gene expression level of several genes that are involved in AD.

Evaluation of preoperative liver function test efficacy in patients with symptomatic cholelithiasis.

AIM: The present study aimed at investigating the necessity of preoperative liver function tests (LFTs) in patients with uncomplicated gallstone disease before laparoscopic cholecystectomy. BACKGROUND: Significant relationship between common bile duct (CBD) stones and acute cholecystitis is reported. There are contradictory reports about the effect of CBD stones on liver function tests in patients (LFTs). METHODS: In the current study, patients with symptomatic cholelithiasis who referred to hospitals during January 2015 and May 2016 were enrolled. Routine tests and ultrasonography were performed on all patients before surgery. Data were presented as means ± SD and qualitative variables as frequency (percentage) were considered. Statistical analyzes were performed with SPSS software. RESULTS: A consecutive series of 270 patients (58 males and 212 females) who referred for laparoscopic cholecystectomy were enrolled in this retrospective study. Pre- operative LFTs were normal in 249 patients (85%) and abnormal LFT was detected in 41 patients (15 %). CONCLUSION: This study showed that 15 % of patients with cholelithiasis without dilated CBD had impaired LFTs. Routine LFTs in preoperative evaluation of symptomatic cholelithiasis usually reveals normal findings and is not helpful in uncomplicated cholelithiasis.

Introducing Serine as Cardiovascular Disease Biomarker Candidate via Pathway Analysis.

BACKGROUND: The rate of death due to cardiovascular disease (CVD) is growing. Investigations about CVD that leading to introduce varieties of metabolites is available. The monitoring of these metabolites to find effective ones in the future of clinic applications is the main aim of this study. MATERIALS AND METHODS: Numbers of 34 metabolites for the CVD are extracted from literature and designated for interaction determinations by MetScape V 3.1.3. The compound-reaction-enzyme-gene network was constructed and the pathways were analyzed. Based on the presence of metabolites in the pathways the critical compounds were determined. RESULTS: Pathway analysis revealed 18 disturbed pathways related to the CVD. glycerophospholipid metabolism pathway including 27 compounds is related to the 9 queried metabolites. L-Serine which was communed between 5 pathways and also was presented in the largest pathway was identified as the critical compound. CONCLUSION: It can be concluded that L-Serine is a proper biomarker candidate for CVD diagnosis and also patients follow up approaches.

Highlighted role of "IL17 signaling pathway" in gastroesophageal reflux disease.

AIM: The aim of this study is to assess the molecular profile of gastroesophageal reflux disease (GERD) via Protein-protein interaction (PPI) network analysis and gene ontology (GO) investigation. BACKGROUND: GERD which affects the life of about 30% of people is associated with high costs in the human papulation. Several risk factors such as smoking, eating habits, BMI, and dysfunction of lower esophageal sphincter have been reported to contribute to the onset and progression of GERD. The roles of some types of interleukins and inflammatory factors as molecular features of GERD are investigated. METHODS: Genes related to GERD were analyzed by Cytoscape v.3.7.2 and the corresponding plug-ins. ClueGO and CluePedia assessed the gene ontology and action type properties for the central nodes. RESULTS: The results indicated that there are 12 hub-bottlenecks almost all of which except ALB are dispersed in the network clusters 1 and 2. Il17 signaling pathway among 7 identified biochemical pathways was also detected as a most related annotation for these central genes. CONCLUSION: Numbers of 11 critical genes and one pathway (IL17 signaling pathway) were highlighted as the deregulate genes and pathway in GERD. Common molecular features of GERD and cancer appeared.

Evaluation of CXCR1 as a possible diagnostic biomarker in acute appendicitis.

AIM: The present study was conducted to determine the genes with common expression in blood and appendix tissue samples in order to introduce them as possible diagnostic biomarkers. BACKGROUND: Diagnosis of acute appendicitis (AA) without applying computed tomographytomography (CT), subjecting the patient to significant radiation, can be surprisingly difficult. Blood circulation may have conscious alterations in its RNA, protein, or metabolite composition. METHODS: The genes related to appendix tissue and blood samples of the patients with AA were extracted from public databases. Fold change (FC) ≥ 2 in blood and FC ≥ 5 in appendix tissue samples were considered to screen differentially expressed genes (DEGs). A protein-protein interaction network was organized using the search tool for retrieval of interacting genes and proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were enriched by DAVID Bioinformatics Resources to find the related biochemical pathways. RESULTS: Among the DEGs in blood and appendix tissue samples, C-X-C motif chemokine receptor 1(CXCR1), leukocyte immunoglobulin-like receptor A3 (LILRA3), low-affinity immunoglobulin gamma Fc region receptor III (FCGR3), and superoxide dismutase 2(SOD2) were common in both sources. CXCR1 was found as only hub gene upregulated in both blood and tissue of the patients with AA compared to controls and those with other abdominal pain. CONCLUSION: CXCR1, FCGR3, LILRA3, and SOD2 were determined as a suitable possible biomarker panel for diagnosis of AA disease.