scholarly journals Screening of disorders associated with osteosarcoma by integrated network analysis

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Yongfeng Dou ◽  
Kai Zhu ◽  
Zhaozhong Sun ◽  
Xiaopeng Geng ◽  
Qingmin Fang
Keyword(s):  
Network Analysis ◽  
Treatment Options ◽  
Enrichment Analysis ◽  
Integrated Network ◽  
Function Enrichment Analysis ◽  
Different Types ◽  
Endogenous Genes ◽  
Regulatory Effects ◽  
Function Enrichment

AbstractOsteosarcoma is a common malignant bone tumor in children and adolescents under the age of 20. However, research on the pathogenesis and treatment of osteosarcoma is still insufficient. In the present study, based on gene-phenotype correlation network, an analysis was performed to screen disorders related to osteosarcoma. First, we analyzed the differential expression of osteosarcoma in two groups according to different types of osteosarcoma and screened the differentially expressed genes (DEGs) related to osteosarcoma. Further, these DEG coexpression modules were obtained. Finally, we identified a series of regulatory factors, such as endogenous genes, transcription factors (TFs), and ncRNAs, which have potential regulatory effects on osteosarcoma, based on the prediction analysis of related network of gene phenotypes. A total of 3767 DEGs of osteosarcoma were identified and clustered them into 20 osteosarcoma-related dysfunction modules. And there were 38 endogenous genes (including ARF1, HSP90AB1, and TUBA1B), 53 TFs (including E2F1, NFKB1, and EGR1), and 858 ncRNAs (including MALAT1, miR-590-3p, and TUG1) were considered as key regulators of osteosarcoma through a series of function enrichment analysis and network analysis. Based on the results of the present study, we can show a new way for biologists and pharmacists to reveal the potential molecular mechanism of osteosarcoma typing, and provide valuable reference for different follow-up treatment options.

scholarly journals Construction of a circRNA-miRNA-mRNA Regulatory Network Reveals Potential Mechanism and Treatment Options for Osteosarcoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi He ◽  
Haiting Zhou ◽  
Wei Wang ◽  
Haoran Xu ◽  
Hao Cheng
Keyword(s):  
Mrna Expression ◽  
Regulatory Network ◽  
Prognostic Value ◽  
Expression Profiles ◽  
Treatment Options ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Primary Bone Tumor ◽  
Function Enrichment Analysis ◽  
Function Enrichment

BackgroundOsteosarcoma is a common malignant primary bone tumor in adolescents and children. Numerous studies have shown that circRNAs were involved in the proliferation and invasion of various tumors. However, the role of circRNAs in osteosarcoma remains unclear. Here, we aimed to explore the regulatory network among circRNA-miRNA-mRNA in osteosarcoma.MethodsThe circRNA (GSE140256), microRNA (GSE28423), and mRNA (GSE99671) expression profiles of osteosarcoma were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs, miRNAs and mRNAs were identified. CircRNA-miRNA interactions and miRNA-mRNA interactions were determined by Circular RNA Interactome (CircInteractome) database and microRNA Data Integration Portal (mirDIP) database, respectively. Then, we constructed a regulatory network. Function enrichment analysis of miRNA and mRNA was performed by DIANA-miRPath v3.0 and Metascape database, respectively. mRNAs with significant prognostic value were identified based on expression profiles from The Cancer Genome Atlas (TCGA) database, and we constructed a subnetwork for them. To make the most of the network, we used the CLUE database to predict potential drugs for the treatment of osteosarcoma based on mRNA expression in the network. And we used the STITCH database to analyze and validate the interactions among these drugs and mRNAs, and to further screen for potential drugs.ResultsA total of 9 circRNAs, 19 miRNAs, 67 mRNAs, 54 pairs of circRNA-miRNA interactions and 110 pairs of miRNA-mRNA interactions were identified. A circRNA-miRNA-mRNA network was constructed. Function enrichment analysis indicated that these miRNAs and mRNAs in the network were involved in the process of tumorigenesis and immune response. Among these mRNAs, STC2 and RASGRP2 with significantly prognostic value were identified, and we constructed a subnetwork for them. Based on mRNA expression in the network, three potential drugs, quinacridine, thalidomide and zonisamide, were screened for the treatment of osteosarcoma. Among them, quinacridine and thalidomide have been proved to have anti-tumor effects in previous studies, while zonisamide has not been reported. And a corresponding drug-protein interaction network was constructed.ConclusionOverall, we constructed a circRNA-miRNA-mRNA regulatory network to investigate the possible mechanism in osteosarcoma, and predicted that quinacridine, thalidomide and zonisamide could be potential drugs for the treatment of osteosarcoma.

scholarly journals Integrative Analysis of Three Novel Competing Endogenous RNA Biomarkers with a Prognostic Value in Lung Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Juan Tan ◽  
Weimin Wang ◽  
Bin Song ◽  
Yingjian Song ◽  
Zili Meng
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Function Enrichment Analysis ◽  
Pathway Function ◽  
Function Enrichment

Increasing evidence has shown competitive endogenous RNAs (ceRNAs) play key roles in numerous cancers. Nevertheless, the ceRNA network that can predict the prognosis of lung adenocarcinoma (LUAD) is still lacking. The aim of the present study was to identify the prognostic value of key ceRNAs in lung tumorigenesis. Differentially expressed (DE) RNAs were identified between LUAD and adjacent normal samples by limma package in R using The Cancer Genome Atlas database (TCGA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway function enrichment analysis was performed using the clusterProfiler package in R. Subsequently, the LUAD ceRNA network was established in three steps based on ceRNA hypothesis. Hub RNAs were identified using degree analysis methods based on Cytoscape plugin cytoHubba. Multivariate Cox regression analysis was implemented to calculate the risk score using the candidate ceRNAs and overall survival information. The survival differences between the high-risk and low-risk ceRNA groups were determined by the Kaplan-Meier and log-rank test using survival and survminer package in R. A total of 2,989 mRNAs, 185 lncRNAs, and 153 miRNAs were identified. GO and KEGG pathway function enrichment analysis showed that DE mRNAs were mainly associated with “sister chromatid segregation,” “regulation of angiogenesis,” “cell adhesion molecules (CAMs),” “cell cycle,” and “ECM-receptor interaction.” LUAD-related ceRNA network was constructed, which comprised of 54 nodes and 78 edges. Top ten hub RNAs (hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-340-5p, hsa-miR-377-3p, hsa-miR-21-5p, hsa-miR-326, SNHG1, RALGPS2, and PITX2) were identified according to their degree. Kaplan-Meier survival analyses demonstrated that hsa-miR-21-5p and RALGPS2 had a significant prognostic value. Finally, we found that a high risk of three novel ceRNA interactions (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) was positively associated with worse prognosis. Three novel ceRNAs (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) might be potential biomarkers for the prognosis and treatment of LUAD.

scholarly journals Regenerative Endodontic Therapy in the Management of Immature Necrotic Permanent Dentition: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Faisal T. Alghamdi ◽  
Alaa E. Alqurashi
Keyword(s):  
Systematic Review ◽  
Treatment Options ◽  
Permanent Teeth ◽  
Maturation Stage ◽  
Exclusion Criteria ◽  
Standardized Protocol ◽  
Case Selection ◽  
Different Types ◽  
Endodontic Regeneration

Background and Objective. Management of immature permanent teeth exhibiting necrotic pulp is clinically challenging. An appropriate diagnosis, case selection, and good management ensure good outcomes. The objective of this review reviews all up-to-date data in regard to endodontic regeneration therapy in the management of immature permanent teeth with necrotic pulp and which conducts are most used and appropriate for this procedure in human and animal investigations. Materials and Methods. The electronic databases PubMed and Google Scholar were used to search the literature for relevant studies after applying specific inclusion and exclusion criteria. Studies that fulfilled both the inclusion and exclusion criteria were included in this systematic review. The search was conducted by two independent reviewers following the PRISMA guidelines. Results. Only 46 studies that fulfilled both the inclusion and exclusion criteria, which were conducted within the last 10 years, were included in this systematic review. These studies investigated different aspects of regenerative endodontic therapy including different types of scaffolds, intracanal medications, pulpal space/barriers, root maturation stage, follow-up duration, and updated studies on their use in the management of immature necrotic permanent teeth. Conclusions. This review concluded the compiled data observed that endodontic regenerative therapy was more efficient in treating immature necrotic permanent teeth and offered a greater advantage that should lead to wider acceptance among endodontists for effective results compared to different treatment options. However, more clinical trials with a standardized protocol and defined clinical, radiographic, and histopathological outcomes with longer follow-up periods are warranted.

Identification and Validation of Glomerulotubular Crosstalk Genes Mediating IgA Nephropathy by Integrated Bioinformatics

2021 ◽  
Author(s):  
Yawen Bai ◽  
Yajing Li ◽  
Yali Xi ◽  
Chunjie Ma
Keyword(s):  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Diagnostic Significance ◽  
Function Enrichment Analysis ◽  
Gene Modules ◽  
Key Genes ◽  
End Stage ◽  
Microarray Datasets ◽  
Geo Database ◽  
Function Enrichment

Abstract BackgroundIgA nephropathy (IgAN), which has been reported as the most prevalent glomerulonephritis globally, is the major contributor to end-stage renal illness. This bioinformatics study aimed to explore glomeruli-tubulointerstitial crosstalk genes and dysregulated pathways relating to the pathogenesis of IgAN. MethodsThe microarray datasets from the Gene Expression Omnibus (GEO) database were searched. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) of both glomeruli and tubulointerstitial were conducted individually. The co-expression gene modules of tubulointerstitial and glomeruli were compared via gene function enrichment analysis. Subsequently, the crosstalk co-expression network was constructed via the STRING database and key genes were mined from the crosstalk network. Results583 DEGs and eight modules were identified in glomeruli samples, while 272 DEGs and four modules were in tubulointerstitial samples. There were 119 overlapping DEGs of the two groups. Among the distinctive modules, four modules in glomeruli and one module in tubulointerstitial were positively associated with IgAN. While four modules in glomeruli and two modules in tubulointerstitial were negatively associated with IgAN. The top ten key genes screened by CytoHubba were ITGAM, ALB, TYROBP, ITGB2, CYBB, HCK, CSF1R, LAPTM5, FN1and CTSS. The above genes were all validated using another two datasets, and all of the key genes demonstrated possible diagnostic significance. Conclusionshe crosstalk genes confirmed in this study may provide novel insight into the pathogenesis of IgAN. Immune-related pathways are associated with both glomerular and tubulointerstitial injuries in IgAN. The glomerulotubular crosstalk might perform a role in the pathogenesis of IgAN.

scholarly journals NMFNA: a non-negative matrix factorization network analysis method for identifying communities and characteristic genes from pancreatic cancer data

2020 ◽  
Author(s):  
Qian Ding ◽  
Yan Sun ◽  
Junliang Shang ◽  
Feng Li ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Network Analysis ◽  
Matrix Factorization ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Bipartite Network ◽  
Analysis Method ◽  
Cancer Data ◽  
Different Types ◽  
Non Negative Matrix Factorization

Abstract Background: Pancreatic cancer (PC) is a common type of digestive system disease. Comprehensive analysis of different types of PC genetic data plays a crucial role in understanding its biological mechanisms. Currently, Non-negative Matrix Factorization (NMF) based methods are widely used for data analysis. Nevertheless, it is a challenge for them to integrate and decompose different types of data simultaneously.Results: In this paper, a Non-negative Matrix Factorization Network Analysis method, NMFNA, is proposed, which introduces a graph regularized constraint to NMF, for identifying communities and characteristic genes from two-type PC data. Firstly, three PC networks, i.e., methylation network (ME), copy number variation network (CNV), and the bipartite network between them, are constructed by both ME and CNV data of PC downloaded from the TCGA database, using the Pearson Correlation Coefficient. Then, the NMFNA is proposed to detect core communities and characteristic genes from these three PC networks effectively due to its introduced graph regularized constraint, which is the highlight of NMFNA. Finally, both gene ontology enrichment analysis and pathway enrichment analysis are performed to deeply understand the biological functions of detected core communities.Conclusions: Experimental results demonstrated that the NMFNA facilitates the integration and decomposition of two types of PC data simultaneously and can serve as an alternative method for detecting communities and characteristic genes from multiple genetic networks. The data and demo codes of NMFNA are available online at https://github.com/CDMB-lab/NMFNA.

scholarly journals Transcriptomic Analysis Reveals the Molecular Adaptation of Three Major Secondary Metabolic Pathways to Multiple Macronutrient Starvation in Tea (Camellia sinensis)

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 241 ◽  
Author(s):  
Hui Su ◽  
Xueying Zhang ◽  
Yuqing He ◽  
Linying Li ◽  
Yuefei Wang ◽  
...  
Keyword(s):  
Camellia Sinensis ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Element Analysis ◽  
Cis Element ◽  
Yield And Quality ◽  
Tea Quality ◽  
Function Enrichment Analysis ◽  
Tea Plants ◽  
Function Enrichment

Tea (Camellia sinensis (L.) O. Kuntze) is a widely consumed beverage. Lack of macronutrients is a major cause of tea yield and quality losses. Though the effects of macronutrient starvation on tea metabolism have been studied, little is known about their molecular mechanisms. Hence, we investigated changes in the gene expression of tea plants under nitrogen (N), phosphate (P), and potassium (K) deficient conditions by RNA-sequencing. A total of 9103 differentially expressed genes (DEG) were identified. Function enrichment analysis showed that many biological processes and pathways were common to N, P, and K starvation. In particular, cis-element analysis of promoter of genes uncovered that members of the WRKY, MYB, bHLH, NF-Y, NAC, Trihelix, and GATA families were more likely to regulate genes involved in catechins, l-theanine, and caffeine biosynthetic pathways. Our results provide a comprehensive insight into the mechanisms of responses to N, P, and K starvation, and a global basis for the improvement of tea quality and molecular breeding.

Antiretroviral Treatment-Associated Labia Majora Lipohypertrophy: A Rare Case and Plastic Surgical Treatment Options

2017 ◽  
Vol 2 (1) ◽  
pp. 43
Author(s):  
Akmal Hisham ◽  
Devananthan Ilenghoven ◽  
Wan Syazli Wan Ahmad Kamal ◽  
Salina Ibrahim ◽  
Shah Jumaat Mohd Yussof
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Daily Living ◽  
Treatment Options ◽  
Hiv Positive ◽  
Highly Active ◽  
Labia Majora ◽  
The Face ◽  
Central Fat

The emergence of highly active antiretroviral therapy (HAART) has revolutionized the prognosis of HIV-infected patients. However, the extended use of HAART is associated with a disfiguring complication termed lipodystrophy, a disorder of body fat maldistribution causing peripheral fat loss (lipoatrophy) and central fat accumulation (lipohypertrophy). Lipoatrophy commonly affects the face, legs, buttocks and arm, whilst lipohypertrophy frequently favours the abdomen, breast and dorsocervical region. To our knowledge, we present only the second documented case in the literature of a labia majora lipohypertrophy in a HIV-positive patient receiving long-term HAART. The severity of labial abnormality caused significant physical and functional morbidities. Labiaplasty with dermolipectomy of the labia majora and excisional lipectomy of the mons pubis was successfully performed. At a 6-month follow-up, patient had no recurrence with resolution of symptoms and resumption of normal activities of daily living (ADL).

Efficacy and safety of oral dapsone in acne vulgaris – experience of a tertiary care teaching hospital in central Lahore

2020 ◽  
Vol 14 (2) ◽  
pp. 87-90
Author(s):  
Sadaf Amin Chaudhry ◽  
Nadia Ali Zafar ◽  
Rabia Hayat ◽  
Ayesha Noreen ◽  
Gulnaz Ali ◽  
...  
Keyword(s):  
Side Effects ◽  
Therapeutic Option ◽  
Acne Vulgaris ◽  
Treatment Options ◽  
Tertiary Care ◽  
Poor Response ◽  
Global Assessment Scale ◽  
Severe Acne ◽  
Hematologic Profile

Background: Acne is the eighth most prevalent disease affecting 9.4% of the population worldwide and its prevalence in our country is estimated to be around 5%. Severe inflammatory acne is most likely to leave scars and in order to prevent facial disfigurement due to acne scarring, early treatment is desirable. Various treatment options have been formulated for acne, and are tailored according to the severity of the disease. Numerous clinical trials have been conducted till now, to determine the usefulness and side effect profile of such therapies, making acne treatment a highly studied area in dermatology. Objective of this study is to highlight the fact that oral Dapsone could be used as a cheaper alternate to isotretinoin in recalcitrant severe acne, especially in females where retinoids are sometimes contraindicated. Patients and methods: 51 patients, suffering from severe nodulocystic acne, fulfilling the criteria, were enrolled from the Department of Dermatology, Sir Ganga Ram Hospital, Lahore. All the study patients were given oral Dapsone 50mg for initial two weeks and then 100mg daily for the next 10 weeks along with oral cimetidine and topical clindamycin application twice daily. Investigator Global Assessment Scale (IGAS) was employed to measure effectiveness. The treatment was considered ʽeffectiveʹ if the patient achieves 2 or more than 2-grade improvement or almost clear or clear skin at the end of 12 weeks according to IGAS scale. The lesion counts were also done before the start of therapy (day 1) and at every two weeks follow up for 12 weeks. The change in lesion count observed between the baseline number and that seen at follow up visits was also used to evaluate the effectiveness of oral Dapsone. Safety was analyzed by fortnightly visits of the patients to look for any undesirable side effects and monitoring of the hematologic profile of the patients. Final follow up was done at the end of 16 weeks. Results: The study was conducted on 51 patients, with a ratio of 1:3 for males and females and a mean age of 25.2 years (SD ±5.81). At 12th week, patients had significant reduction in their acne lesions; with 7 patients (13.7%) showing completely clear skin, 17 patients (33.3%) had almost clear skin, 5 patients (9.8%) had 3-grade improvement. Twelve patients (23.5%) had 2-grade improvement from baseline score and only 2 patients (3.9%) had 1-grade improvement from baseline. Based on percentage reduction of lesions, excellent response was seen in 32 patients (62.7%), good response in 9 patients (17.6%), moderate response in 2 patients (3.9%), while no patient showed poor response. Dapsone was discontinued in 8 patients due to derangement of hematologic profile. Conclusion: Oral Dapsone, when given carefully, is a very effective therapeutic option in severe recalcitrant acne, with limited side effects.

In Silico Protein Interaction Network Analysis of Virulence Proteins Associated with Invasive Aspergillosis for Drug Discovery

2019 ◽  
Vol 19 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Renu Chaudhary ◽  
Meenakshi Balhara ◽  
Deepak Kumar Jangir ◽  
Mehak Dangi ◽  
Mrridula Dangi ◽  
...  
Keyword(s):  
Network Analysis ◽  
Invasive Aspergillosis ◽  
Protein Interaction ◽  
Drug Target ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Homology Model ◽  
Ppi Network ◽  
Virulence Proteins ◽  
Hub Proteins

<P>Background: Protein-Protein interaction (PPI) network analysis of virulence proteins of Aspergillus fumigatus is a prevailing strategy to understand the mechanism behind the virulence of A. fumigatus. The identification of major hub proteins and targeting the hub protein as a new antifungal drug target will help in treating the invasive aspergillosis. </P><P> Materials & Method: In the present study, the PPI network of 96 virulence (drug target) proteins of A. fumigatus were investigated which resulted in 103 nodes and 430 edges. Topological enrichment analysis of the PPI network was also carried out by using STRING database and Network analyzer a cytoscape plugin app. The key enriched KEGG pathway and protein domains were analyzed by STRING.Conclusion:Manual curation of PPI data identified three proteins (PyrABCN-43, AroM-34, and Glt1- 34) of A. fumigatus possessing the highest interacting partners. Top 10% hub proteins were also identified from the network using cytohubba on the basis of seven algorithms, i.e. betweenness, radiality, closeness, degree, bottleneck, MCC and EPC. Homology model and the active pocket of top three hub proteins were also predicted.</P>

Determination of Usnic Acid Responsive miRNAs in Breast Cancer Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1463-1472 ◽  
Author(s):  
Nil Kiliç ◽  
Yasemin Ö. Islakoğlu ◽  
İlker Büyük ◽  
Bala Gür-Dedeoğlu ◽  
Demet Cansaran-Duman
Keyword(s):  
Breast Cancer ◽  
Hedgehog Signaling ◽  
Treatment Options ◽  
Usnic Acid ◽  
Enrichment Analysis ◽  
Breast Cancer Cell Lines ◽  
Pathway Enrichment Analysis ◽  
Molecular Heterogeneity ◽  
Proliferative Effect ◽  
Mcf 7

Objective: Breast Cancer (BC) is the most common type of cancer diagnosed in women. A common treatment strategy for BC is still not available because of its molecular heterogeneity and resistance is developed in most of the patients through the course of treatment. Therefore, alternative medicine resources as being novel treatment options are needed to be used for the treatment of BC. Usnic Acid (UA) that is one of the secondary metabolites of lichens used for different purposes in the field of medicine and its anti-proliferative effect has been shown in certain cancer types, suggesting its potential use for the treatment. Methods: Anti-proliferative effect of UA in BC cells (MDA-MB-231, MCF-7, BT-474) was identified through MTT analysis. Microarray analysis was performed in cells treated with the effective concentration of UA and UA-responsive miRNAs were detected. Their targets and the pathways that they involve were determined using a miRNA target prediction tool. Results: Microarray experiments showed that 67 miRNAs were specifically responsive to UA in MDA-MB-231 cells while 15 and 8 were specific to BT-474 and MCF-7 cells, respectively. The miRNA targets were mostly found to play role in Hedgehog signaling pathway. TGF-Beta, MAPK and apoptosis pathways were also the prominent ones according to the miRNA enrichment analysis. Conclusion: The current study is important as being the first study in the literature which aimed to explore the UA related miRNAs, their targets and molecular pathways that may have roles in the BC. The results of pathway enrichment analysis and anti-proliferative effects of UA support the idea that UA might be used as a potential alternative therapeutic agent for BC treatment.

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