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1.
Exp Eye Res ; 231: 109488, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37116607

RESUMO

Keratoconus (KC) is a multifactorial disease in which genetic factors played important roles in its pathogenesis. The purpose of the current study was to identify the key candidate genes and pathways in Chinese patients with KC through bioinformatics analysis. Totally, we identified 71 candidate genes by analyzing the results of whole exome sequencing on 51 Chinese patients with KC, combining with previous reports on differential expression at transcription and protein levels in KC. Gene enrichment analysis with GeneCodis demonstrated that two significantly enriched terms including 21 genes in biological process (BP) were detected, and six significantly enriched terms containing 14 genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were discovered. The STRING was utilized to construct the protein-protein interaction (PPI) network of identified genes. The result showed that a PPI network consisted of 14 nodes with 14 edges was constructed, and two gene modules were obtained. Eight hub genes (LAMB3, LAMA3, LAMA1, ITGA6, ITGA3, COL6A3, COL6A2, and COL6A1) were identified as key candidate genes for KC by cytoHubba in Cytoscape. Functional enrichment analysis with ClueGO and CluePedia indicated that the ECM-receptor interaction was the key pathway accounted for KC. The findings might provide novel insights on the genetic basis of KC.


Assuntos
Perfilação da Expressão Gênica , Ceratocone , Humanos , Perfilação da Expressão Gênica/métodos , Ceratocone/genética , População do Leste Asiático , Mapas de Interação de Proteínas/genética , Biologia Computacional/métodos
2.
Ren Fail ; 45(1): 2199095, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37038746

RESUMO

Diabetic nephropathy (DN) is the primary complication of diabetes mellitus. Ferroptosis is a form of cell death that plays an important role in DN tubulointerstitial injury, but the specific molecular mechanism remains unclear. Here, we downloaded the DN tubulointerstitial datasets GSE104954 and GSE30529 from the Gene Expression Omnibus database. We examined the differentially expressed genes (DEGs) between DN patients and healthy controls, and 36 ferroptosis-related DEGs were selected. Pathway-enrichment analyses showed that many of these genes are involved in metabolic pathways, phosphoinositide 3-kinase/Akt signaling, and hypoxia-inducible factor-1 signaling. Ten of the 36 ferroptosis-related DEGs (CD44, PTEN, CDKN1A, DPP4, DUSP1, CYBB, DDIT3, ALOX5, VEGFA, and NCF2) were identified as key genes. Expression patterns for six of these (CD44, PTEN, DDIT3, ALOX5, VEGFA, and NCF2) were validated in the GSE30529 dataset. Nephroseq data indicated that the mRNA expression levels of CD44, PTEN, ALOX5, and NCF2 were negatively correlated with the glomerular filtration rate (GFR), while VEGFA and DDIT3 mRNA expression levels were positively correlated with GFR. Immune infiltration analysis demonstrated altered immunity in DN patients. Real-time quantitative PCR (qPCR) analysis showed that ALOX5, PTEN, and NCF2 mRNA levels were significantly upregulated in high-glucose-treated human proximal tubular (HK-2) cells, while DDIT3 and VEGFA mRNA levels were significantly downregulated. Immunohistochemistry analysis of human renal biopsies showed positive staining for ALOX5 and NCF2 protein in DN samples but not the controls. These key genes may be involved in the molecular mechanisms underlying ferroptosis in patients with DN, potentially through specific metabolic pathways and immune/inflammatory mechanisms.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Ferroptose , Humanos , Biologia Computacional , Nefropatias Diabéticas/patologia , Ferroptose/genética , Fosfatidilinositol 3-Quinases , RNA Mensageiro/metabolismo , Nefrite Intersticial
3.
Curr Issues Mol Biol ; 44(8): 3552-3572, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36005140

RESUMO

Oral cancer (OC) is a serious health concern that has a high fatality rate. The oral cavity has seven kinds of OC, including the lip, tongue, and floor of the mouth, as well as the buccal, hard palate, alveolar, retromolar trigone, and soft palate. The goal of this study is to look into new biomarkers and important pathways that might be used as diagnostic biomarkers and therapeutic candidates in OC. The publicly available repository the Gene Expression Omnibus (GEO) was to the source for the collection of OC-related datasets. GSE74530, GSE23558, and GSE3524 microarray datasets were collected for analysis. Minimum cut-off criteria of |log fold-change (FC)| > 1 and adjusted p < 0.05 were applied to calculate the upregulated and downregulated differential expression genes (DEGs) from the three datasets. After that only common DEGs in all three datasets were collected to apply further analysis. Gene ontology (GO) and pathway analysis were implemented to explore the functional behaviors of DEGs. Then protein−protein interaction (PPI) networks were built to identify the most active genes, and a clustering algorithm was also implemented to identify complex parts of PPI. TF-miRNA networks were also constructed to study OC-associated DEGs in-depth. Finally, top gene performers from PPI networks were used to apply drug signature analysis. After applying filtration and cut-off criteria, 2508, 3377, and 670 DEGs were found for GSE74530, GSE23558, and GSE3524 respectively, and 166 common DEGs were found in every dataset. The GO annotation remarks that most of the DEGs were associated with the terms of type I interferon signaling pathway. The pathways of KEGG reported that the common DEGs are related to the cell cycle and influenza A. The PPI network holds 88 nodes and 492 edges, and CDC6 had the highest number of connections. Four clusters were identified from the PPI. Drug signatures doxorubicin and resveratrol showed high significance according to the hub genes. We anticipate that our bioinformatics research will aid in the definition of OC pathophysiology and the development of new therapies for OC.

4.
Mol Cell Oncol ; 10(1): 2246657, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593751

RESUMO

GBM is the most common and aggressive type of brain tumor. It is classified as a grade IV tumor by the WHO, the highest grade. Prognosis is generally poor, with most patients surviving only about a year. Only 5% of patients survive longer than 5 years. Understanding the molecular mechanisms that drive GBM progression is critical for developing better diagnostic and treatment strategies. Identifying key genes involved in GBM pathogenesis is essential to fully understand the disease and develop targeted therapies. In this study two datasets, GSE108474 and GSE50161, were obtained from the Gene Expression Omnibus (GEO) to compare gene expression between GBM and normal samples. Differentially expressed genes (DEGs) were identified and analyzed. To construct a protein-protein interaction (PPI) network of the commonly up-regulated and down-regulated genes, the STRING 11.5 and Cytoscape 3.9.1 were utilized. Key genes were identified through this network analysis. The GEPIA database was used to confirm the expression levels of these key genes and their association with survival. Functional and pathway enrichment analyses on the DEGs were conducted using the Enrichr server. In total, 698 DEGs were identified, consisting of 377 up-regulated genes and 318 down-regulated genes. Within the PPI network, 11 key up-regulated genes and 13 key down-regulated genes associated with GBM were identified. NOTCH1, TOP2A, CD44, PTPRC, CDK4, HNRNPU, and PDGFRA were found to be important targets for potential drug design against GBM. Additionally, functional enrichment analysis revealed the significant impact of Epstein-Barr virus (EBV), Cell Cycle, and P53 signaling pathways on GBM.

5.
World J Clin Cases ; 11(23): 5468-5478, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37637683

RESUMO

BACKGROUND: Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome (PCOS). However, the effectiveness of vitamin, vitamin-like nutrient, or mineral supplementation in reducing the risk of PCOS remains a subject of debate. AIM: To investigate the impact of plasma levels of vitamins A, B12, D, E, and K on PCOS and key pathways implicated in its development, namely, insulin resistance, hyperlipidemia, and obesity, through Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies. The primary analysis was performed using the random-effects inverse-variance-weighted approach. Complementary analyses were conducted using the weighted median, MR-Egger, MR-robust adjusted profile score, and MR-PRESSO approaches. RESULTS: The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E (odds ratio [OR] = 0.118; 95% confidence interval [CI]: 0.071-0.226; P < 0.001) and vitamin B12 (OR = 0.753, 95%CI: 0.568-0.998, P = 0.048). An association was observed between vitamin E levels and insulin resistance (OR = 0.977, 95%CI: 0.976-0.978, P < 0.001). Additionally, genetically predicted higher concentrations of vitamins E, D, and A were suggested to be associated with a decreased risk of hyperlipidemia. Increased vitamins K and B12 levels were linked to a lower obesity risk (OR = 0.917, 95%CI: 0.848-0.992, P = 0.031). CONCLUSION: The findings of this MR study suggest a causal relationship between increased vitamins A, D, E, K, and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.

6.
Front Vet Sci ; 9: 1016191, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504863

RESUMO

The oviduct consists of three parts: the infundibulum (In), ampulla (Am), and isthmus (Is). These have the same histological structure, but different physiological functions. In this study, transcriptomics was used to analyze mRNA in these three parts of yak oviduct. The results showed that there were 325 up-regulated genes and 282 down-regulated genes in the infundibulum and ampulla. Moreover, there were 234 up-regulated genes and 776 down-regulated genes in the isthmus and ampulla, as well as 873 up-regulated genes and 297 down-regulated genes in the infundibulum and isthmus. The expression of C3 in the infundibulum was significantly higher than that in the ampulla and isthmus. The expression of FAU in the isthmus was significantly lower than that in the ampulla and infundibulum, and the expression of EEF1A1 in the ampulla was significantly higher than that in the ampulla and infundibulum. When the infundibulum was compared with the ampulla and isthmus, it was found that the up-regulated genes were enriched in the lysosome, phagosome, staphylococcus aureus infection, and leishmaniasis pathway. When the isthmus was compared with the ampulla and infundibulum, the up-regulated genes were present in the apoptosis pathway, oxidative phosphorylation, and viral myocarditis pathway. When the isthmus was compared with the infundibulum and ampulla, the down-regulated pathways were protein processing in the endoplasmic reticulum and the endocytosis. The Epstein-Barr virus infection pathway was up-regulated according to a comparison of the isthmus and infundibulum and was down-regulated based on a comparison of the isthmus and ampulla. Transcriptional misregulation in the Middle East pathway was up-regulated based on a comparison of the isthmus and ampulla and was down-regulated based on a comparison of the isthmus and infundibulum. ERBB2, JUP, CTNND1, and KRT7 were defined as the hub genes of the yak oviduct. The results of this study provide sufficient omics data for yak fertilization, which is also of great significance to altitude medicine.

7.
BMC Genom Data ; 23(1): 35, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538407

RESUMO

BACKGROUND: Adipose tissues (ATs), including visceral ATs (VATs) and subcutaneous ATs (SATs), are crucial for maintaining energy and metabolic homeostasis. SATs have been found to be closely related to obesity and obesity-induced metabolic disease. Some studies have shown a significant association between subcutaneous fat metabolism and sexes. However, the molecular mechanisms for this association are still unclear. Here, using the pig as a model, we investigated the systematic association between the subcutaneous fat metabolism and sexes, and identified some key sex-specific pathways and genes in the SATs from pigs. RESULTS: The results revealed that 134 differentially expressed genes (DEGs) were identified in female and male pigs from the obese group. A total of 17 coexpression modules were detected, of which six modules were significantly correlated with the sexes (P < 0.01). Among the significant modules, the greenyellow module (cor = 0.68, P < 9e-06) and green module (cor = 0.49, P < 0.003) were most significantly positively correlated with the male and female, respectively. Functional analysis showed that one GO term and four KEGG pathways were significantly enriched in the greenyellow module while six GO terms and six KEGG pathways were significantly enriched in the green module. Furthermore, a total of five and two key sex-specific genes were identified in the two modules, respectively. Two key sex-specific pathways (Ras-MAPK signaling pathway and type I interferon response) play an important role in the SATs of males and females, respectively. CONCLUSIONS: The present study identified some key sex-specific pathways and genes in the SATs from pigs, which provided some new insights into the molecular mechanism of being involved in fat formation and immunoregulation between pigs of different sexes. These findings may be beneficial to breeding in the pig industry and obesity treatment in medicine.


Assuntos
Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Tecido Adiposo , Animais , Feminino , Perfilação da Expressão Gênica/métodos , Masculino , Obesidade/genética , Gordura Subcutânea , Suínos/genética
8.
Adv Cancer Res ; 152: 67-102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34353444

RESUMO

Head and neck cancers are a heterogeneous, aggressive and genetically complex collection of malignancies of the oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinuses and salivary glands, which are difficult to treat. About 90% of all head and neck cancers are squamous cell carcinomas (HNSCC). Larynx and Oral cavity carcinomas are generally related with tobacco consumption, alcohol abuse (or both), but pharynx carcinomas are generally associated with infection of human papillomavirus (HPV), especially HPV-16 subtype. Thus, usually HNSCC can be separated into HPV-negative and HPV-positive categories. Despite substantial efforts invested into therapeutic development of HNSCC, the 5-year survival rate of patients with HNSCC still remains dismal. The primary reason being late diagnosis, recurrent metastasis, relapse and resistance to therapies. Currently surgery and radiotherapy represent the baseline treatment options for most initial stage HNSCC patients, but these treatments are associated with significant morbidity and poor prognosis. Moreover, the issue of resistance to both radiotherapy/chemotherapy and recurrent relapse are common in HNSCC. Elucidation of the genetic landscape, tumor microenvironment and aberrant signaling pathways have generated new insights into the molecular pathogenesis of this disease. Thus, the scientific research has therefore been focused on the understanding of HNSCC biology and immunobiology to identification of predictive/prognostic biomarkers, which will be key to develop more effective targeted therapies with less toxicity and high specificity.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Papillomaviridae , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral
9.
Transl Cancer Res ; 10(5): 2399-2408, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-35116555

RESUMO

BACKGROUND: Despite recent advances in screening, treatment, and survival, breast cancer remains the most invasive cancer in women. The development of novel diagnostic and therapeutic markers for breast cancer may provide more information about its pathogenesis and progression. METHODS: We obtained GSE86374 micro-expression matrix chip data from the Gene Expression Omnibus (GEO) database consisting of 159 samples (124 normal samples and 35 breast cancer samples). The language was then used to perform data processing and differential expression analysis. For all differentially expressed genes (DEGs), "FDR <0.01 and |logFC| ≥1" were selected as thresholds. RESULTS: In this study, 173 up-regulated genes and 143 down-regulated genes were selected for GO and KEGG enrichment analysis. These genes are also significantly enriched in the KEGG pathway, including phenylalanine metabolism, staphylococcus aureus infection, and the PPAR signaling pathway. The survival and prognosis of the selected eight key genes (DLGAP5, PRC1, TOP2A, CENPF, RACGAP1, RRM2, PLK1, and ASPM) were analyzed by the Kaplan-Meier plotter database. CONCLUSIONS: Eight hub genes and pathways closely related to the onset and progression of breast cancer were identified. We found that the PPAR signaling pathway, especially PPARγ, plays an important role in breast cancer and suggest this pathway be the subject of further research.

10.
Sci Total Environ ; 760: 143326, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33223183

RESUMO

With the greatly increased demand for animal products, the global dairy sector has experienced rapid expansion and intensification. The correspondingly increasing manure and sewage produced has been the major contributor to environmental burden and human health, especially in developing countries like China. Both worldwide environmental concerns and growing awareness of the circular economy have focused the governments' attention on environmental policies related to sustainable manure and sewage management (MSM). However, inherently dynamic decision-making processes of individual farms result in a great diversity of MSM practices, which leads to enormous difficulties and complexity in further sustainability and policy evaluation. Hence, it is essential to explore the key MSM pathways to represent diversity at a scientific and statistic view. While it is rarely practiced, particularly in China's dairy farming. We used China as a case study to develop the key MSM pathways using data from the nationwide survey of 306 scale dairy farms via a quantitative typology methodology. The results by optimal clustering solution revealed four key pathways based on the individual practices which are associated with the collection, storage, and processing and utilization stages. Furthermore, general characteristics were compared to identify potential determinant factors. It revealed that the major indicators such as resource endowments, milk productivity and quality, and revenues and expenditure showed a consistently increasing trend among pathways. The results indicated resource availability and intensive degree, to a certain extent, affected the farmers' selection. The possibilities of performing sustainability and policy evaluation at a higher scale were also demonstrated. Overall, the identified key pathways can help to know regional waste utilization and economic potential to evolve their MSM strategies. They are especially critical for developing countries to obtain typical MSM profiles and formulate targeted policies more effectively, aiming to promote dairy sustainable development and achieve the circular economy globally.

11.
Ann Transl Med ; 8(24): 1682, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33490194

RESUMO

BACKGROUND: Spinal cord injuries (SCIs), along with subsequent secondary injuries, often result in irreversible damage to both sensory and motor functions. However, a thorough view of the underlying pathological mechanisms of SCIs, especially in a temporal-spatial manner, is still lacking. METHODS: To obtain a comprehensive, real-time view of multiple subsets of the cellular mechanisms involved in SCIs, we applied RNA-sequencing technology to characterize the temporal changes in gene expression around the lesion site of contusion SCI in rats. First, we identified the differentially expressed genes (DEGs) in contrast to sham controls at 1, 4, and 7 days post SCI. Through bioinformatics analysis, including Pathway analysis, Gene-act-net, and Pathway-act-net, we screened and verified potential key pathways and genes associated with either the acute or subacute stages of SCI pathology. RESULTS: The top three overrepresented pathways were associated with cytokine-cytokine receptor interaction, TNF signaling pathway, and cell cycle at day 1; lysosome, cytokine-cytokine receptor interaction, phagosome at day 4; and phagosome, lysosome, cytokine-cytokine receptor interaction at day 7 post injury. Further, we identified uniquely enriched genes at each time point, such as Ccr1 and Nos2 at day 1; as well as Mgst2, and Pla2g3 at 4 and 7 days post-injury. CONCLUSIONS: Our pathway analysis suggested a transition from inflammatory responses to multiple forms of cell death processes from the acute to subacute stages of SCI. Further, our results revealed a continuous transformation from a more inflammatory to an apoptotic/self-repairing transcriptome following the time-course of SCIs. Our research provides novel insights into the molecular mechanisms of SCI pathophysiology and identifies potential targets for therapeutic intervention after SCI.

12.
Artif Cells Nanomed Biotechnol ; 48(1): 999-1007, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32589050

RESUMO

Background: Intracranial aneurysm (IA) is a disease resulted from weak brain control, characterized by local expansion or dilation of brain artery. This study aimed to construct a gene co-expression network by Weighted Gene Correlation Network Analysis (WGCNA) to explore the potential key pathways and genes for the development of IA.Method: Six IA-related gene expression data sets were downloaded from the Gene Expression Omnibus (GEO) database for identifying differentially expressed genes (DEGs). WGCNA was used to identify modules associated with IA. Functional enrichment analysis was used to explore the potential biological functions. ROC analysis was used to find markers for predicting IA.Results: Purple, greenyellow and yellow modules were significantly associated with unruptured intracranial aneurysms, while blue and turquoise modules were significantly associated with ruptured intracranial aneurysms. Functional modules significantly related to IA were enriched in Ribosome, Glutathione metabolism, cAMP signalling pathway, Lysosome, Glycosaminoglycan degradation and other pathways. CD163, FCEREG, FPR1, ITGAM, NLRC4, PDG, and TYROBP were up-regulated ruptured intracranial aneurysms and serum, these genes were potential circulating markers for predicting IA rupture.Conclusions: Potential IA-related key pathways, genes and circulating markers were identified for predicting IA rupture by WGCNA analysis.


Assuntos
Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/genética , Biomarcadores/sangue , Análise por Conglomerados , Humanos
13.
Front Psychol ; 10: 302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873067

RESUMO

Introduction: Post-traumatic stress disorder (PTSD) is characterized by impaired fear extinction, excessive anxiety, and depression. However, the potential pathogenesis and cause of PTSD are not fully understood. Hence, the purpose of this study was to identify key genes and pathway involved in PTSD and reveal underlying molecular mechanisms by using bioinformatics analysis. Methods: The mRNA microarray expression profile dataset was retrieved and downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened using GEO2R. Gene ontology (GO) was used for gene function annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was performed for enrichment analysis. Subsequently, protein-protein interaction (PPI) network and module analysis by the plugin MCODE were mapped by Cytoscape software. Finally, these key genes were verified in stress-exposed models by Real-Time quantitative (qRT-PCR). In addition, we performed text mining among the key genes and pathway with PTSD by using COREMINE. Results: A total of 1004 DEGs were identified. Gene functional annotations and enrichment analysis indicated that the most associated pathway was closely related to the Wnt signaling pathway. Using PPI network and module analysis, we identified a group of "seed" genes. These genes were further verified by qRT-PCR. In addition, text mining indicated that the altered CYP1A2, SYT1, and NLGN1 affecting PTSD might work via the Wnt signaling pathway. Conclusion: By using bioinformatics analysis, we identified a number of genes and relevant pathway which may represent key mechanisms associated with PTSD. However, these findings require verification in future experimental studies.

14.
Oncol Lett ; 17(6): 5608-5618, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31186783

RESUMO

The aim of the present study was to analyze lung adenocarcinoma-associated microarray data and identify potentially crucial genes. The gene expression profiles were downloaded from the Gene Expression Omnibus database and 6 datasets, of which 2 were discarded and 4 were retained, were preprocessed using packages in the R computing language. Subsequently, Gene Set Enrichment Analysis (GSEA) and meta-analysis was used to screen the common pathways and differentially expressed genes at the transcriptional level. The genes detected from GSEA through The Cancer Genome Atlas databases were subsequently examined, and the crucial genes by survival data were identified. Pathways of the crucial genes were obtained using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the online website Database for Annotation, Visualization and Integrated Discovery (DAVID) tool, and the pathways of crucial genes that were upregulated or downregulated were matched using the Venn method to identify the common crucial pathways. Furthermore, on the basis of the common crucial pathways, key genes that are closely associated with the development and progression of lung adenocarcinoma were identified with the KEGG pathway of DAVID. Additional information was obtained through Gene Ontology annotation. A total of two key pathways, including cell cycle and DNA replication, as well as 12 key genes [DNA polymerase δ subunit 2, DNA replication licensing factor MCM4, MCM6, mitotic checkpoint serine/threonine-protein kinase BUB1, BUB1ß, mitotic spindle assembly checkpoint protein MAD2A, dual specificity protein kinase TTK, M-phase inducer phosphatase 1, cell division control protein 45 homolog, cyclin-dependent kinase inhibitor 1C, pituitary tumor-transforming gene 1 protein and polo-like kinase 1] were identified. These key pathways and genes may be studied in future studies involving gene transfection/knockdown, which may provide insights into the prognosis of lung adenocarcinoma. Additional studies are required to confirm their biological function.

15.
Gene ; 661: 85-94, 2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-29601948

RESUMO

PURPOSE: This study aimed to screen key genes and pathways involved in obese polycystic ovary syndrome (PCOS), and predict drugs for treatment of obese PCOS via bioinformatics approaches. METHODS: Microarray dataset GSE10946 were downloaded from the Gene Expression Omnibus database, including 7 cumulus cell samples from obese PCOS patients and 6 lean control samples. Differentially expressed genes (DEGs) between obese PCOS and controls were obtained using Bayesian test after data preprocessing, followed by functional enrichment analyses for DEGs. Besides, protein-protein interaction (PPI) network and sub-network analyses were performed. Furthermore, drug prediction was carried out based on the DEGs. RESULTS: A total of 793 DEGs were identified in PCOS compared with control, including 352 up-regulated and 441 down-regulated DEGs. Specifically, upregulated RNA polymerase I subunit B (POLR1B), DNA polymerase epsilon 3, accessory subunit (POLE3), and DNA polymerase delta 3, accessory subunit (POLD3) were enriched in pathway of pyrimidine metabolism associated with obesity and PCOS, and 5-hydroxytryptamine receptor 2C (HTR2C) was enriched calcium signaling pathway. Additionally, 10 significant potential drugs, such as spironolactone targeting androgen receptor (AR), trimipramine targeting adrenoceptor beta 2 (ADRB2), and L-ornithine targeting ornithine decarboxylase antizyme 3 (OAZ3), were obtained. CONCLUSIONS: In conclusion, POLR1B, POLE3, POLD3, and HTR2C might play important roles in obese PCOS via involvement of pyrimidine metabolism and calcium signaling pathway. Moreover, AR, ADRB2, and OAZ3 might be targets of spironolactone, trimipramine, and L-ornithine in the treatment of obese PCOS.


Assuntos
Biomarcadores Farmacológicos/análise , Resistência a Medicamentos/genética , Genes Reguladores , Obesidade/genética , Síndrome do Ovário Policístico/genética , Adulto , Biomarcadores Farmacológicos/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Análise em Microsséries , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Prognóstico , Transdução de Sinais/genética , Adulto Jovem
16.
Artigo em Chinês | WPRIM | ID: wpr-802440

RESUMO

Objective: To study on the molecular mechanism of anti-platelet aggregation and anti-thrombosis of Sparganii Rhizoma. Method: Based on the data information and analysis functions of traditional Chinese medicine(TCM) database,TCM composition database and target database in TCM platform for integration of pharmacology,information of chemical compositions in Sparganii Rhizoma was retrieved,interaction network between potential targets of Sparganii Rhizoma and disease targets was built,and the key targets were enriched and calculated,the gene functions and pathways were analyzed,multidimensional relationship network of " herbal medicines-chemical components-key targets-key pathways" was built. Result: Active ingredients of Sparganii Rhizoma mainly included flavonoids and phenolic acids,such as mountain kaempferol,sanleng acid,linoleic acid,etc.Anti-thrombosis involved 202 key targets,including protein kinase Cδ(PRKCD),glucose kinase(GCK),(PRKAA2),adenosine ribonucleotide activated protein kinase α-2 catalytic subunit,etc;and it was related to the endocrine system,circulatory system,neurodegenerative diseases and other related biological processes and signal pathways.Anti-platelet aggregation involved 136 key targets,including PRKCD,cytochrome C oxidase protein 7C(COX7C),GCK,etc;and it was involved in Parkinson's disease,circulatory system,neurodegenerative diseases and other related biological processes and signal pathways. Conclusion: Sparganii Rhizoma regulates vascular endothelial cell adhesion molecule expression and platelet mitochondrial function mediated apoptosis of platelets mainly through regulating neurotransmitter activity in the central nervous system,in order to exert antithrombotic effect and anti-platelet aggregation effect.

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