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1.
Sci Rep ; 14(1): 12532, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822007

RESUMO

This paper aims to estimate the permeability of concrete by replacing the laboratory tests with robust machine learning (ML)-based models. For this purpose, the potential of twelve well-known ML techniques was investigated in estimating the water penetration depth (WPD) of nano natural pozzolana (NNP)-reinforced concrete based on 840 data points. The preparation of concrete specimens was based on the different combinations of NNP content, water-to-cement (W/C) ratio, median particle size (MPS) of NNP, and curing time (CT). Comparing the results estimated by the ML models with the laboratory results revealed that the hist-gradient boosting regressor (HGBR) and K-nearest neighbors (KNN) algorithms were the most and least robust models to estimate the WPD of NNP-reinforced concrete, respectively. Both laboratory and ML results showed that the WPD of NNP-reinforced concrete decreased with the increase of the NNP content from 1 to 4%, the decrease of the W/C ratio and the MPS, and the increase of the CT. To further aid in the estimation of concrete's WPD for engineering challenges, a graphical user interface for the ML-based models was developed. Proposing such a model may be effectively employed in the management of concrete quality.

2.
Environ Sci Pollut Res Int ; 30(60): 126057-126071, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38008840

RESUMO

Gabions involve low construction technology and are flexible, economically viable, and environmentally friendly. They are now widely accepted as a standard construction material on a global scale. Gabion water barrier structures can be used for a variety of objectives, including flood control, land development, regulation of sediment transport, and catchment restoration. While intense water runoff can cause a large hole or submerge regions in solid water barrier constructions, gabion structures can sink down into the earth and protect the land from environmental and economic damage. The present study reviews the design/construction procedure of gabion water barrier structures and field/laboratory and numerical investigations for their performance in water and land conservation. Various applications of gabion water barrier structures, especially for economic/social impact and environmental degradation control, which qualify the gabion water barrier structures as a sustainable technique for water and land conservation, are reviewed. Future aspects and challenges ahead are also discussed.


Assuntos
Conservação dos Recursos Naturais , Água , Conservação dos Recursos Naturais/métodos , Materiais de Construção
3.
Front Microbiol ; 14: 1104490, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37200920

RESUMO

Rhizosphere is the battlefield of beneficial and harmful (so called phytopathogens) microorganisms. Moreover, these microbial communities are struggling for their existence in the soil and playing key roles in plant growth, mineralization, nutrient cycling and ecosystem functioning. In the last few decades, some consistent pattern have been detected so far that link soil community composition and functions with plant growth and development; however, it has not been studied in detail. AM fungi are model organisms, besides potential role in nutrient cycling; they modulate biochemical pathways directly or indirectly which lead to better plant growth under biotic and abiotic stress conditions. In the present investigations, we have elucidated the AM fungi-mediated activation of plant defense responses against Meloidogyne graminicola causing root-knot disease in direct seeded rice (Oryza sativa L.). The study describes the multifarious effects of Funneliformis mosseae, Rhizophagus fasciculatus, and Rhizophagus intraradices inoculated individually or in combination under glasshouse conditions in rice plants. It was found that F. mosseae, R. fasciculatus and R. intraradices when applied individually or in combination modulated the biochemical and molecular mechanisms in the susceptible and resistant inbred lines of rice. AM inoculation significantly increased various plant growth attributes in plants with simultaneous decrease in the root-knot intensity. Among these, the combined application of F. mosseae, R. fasciculatus, and R. intraradices was found to enhance the accumulation and activities of biomolecules and enzymes related to defense priming as well as antioxidation in the susceptible and resistant inbred lines of rice pre-challenged with M. graminicola. The application of F. mosseae, R. fasciculatus and R. intraradices, induced the key genes involved in plant defense and signaling and it has been demonstrated for the first time. Results of the present investigation advocated that the application of F. mosseae, R. fasciculatus and R. intraradices, particularly a combination of all three, not only helped in the control of root-knot nematodes but also increased plant growth as well as enhances the gene expression in rice. Thus, it proved to be an excellent biocontrol as well as plant growth-promoting agent in rice even when the crop is under biotic stress of the root-knot nematode, M. graminicola.

4.
Biotechnol Genet Eng Rev ; : 1-20, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696368

RESUMO

Leprosy is a major health concern and continues to be a source of fear and stigma among people worldwide. Despite remarkable achievements in the treatment, understanding of pathogenesis and transmission, epidemiology of leprosy still remains inadequate. The prolonged incubation period, slow rates of occurrence in those exposed and deceptive clinical presentation pose challenges to develop reliable strategies to stop transmission. Hence, there is a need for improved diagnostics and therapies to prevent mortality caused by leprosy. The objectives of this study are to identify significant genes from protein-protein interactions (PPIs) network of leprosy and to choose the most effective therapeutic targets. Fifty genes related with leprosy were discovered by literature mining. These genes were used to construct a primary network. Leading Eigen Vector method was used to break down the primary network into various sub-networks or communities. It was found that the primary network was divided into many sub-networks at the 6 levels. Seed genes were traced at each level till key regulatory genes were identified. Three seed genes, namely, GNAI3, NOTCH1, and HIF1A, were able to make their way till the final motif stage. These genes along with their interacting partners were considered key regulators of the leprosy network. This study provides leprosy-associated key genes which can lead to improved diagnosis and therapies for leprosy patients.

5.
Glob Ment Health (Camb) ; 10: e81, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38161739

RESUMO

Background: Due to the Jammu and Kashmir conflict, many teenagers are involved in disputes with the law. The conflict made generations suffer for decades. Such children made the mobs; being involved in life-threatening situations and the risk they confront develop psychiatric disorders. As a result of the various tense conditions when applied in multiple anti-social activities, aberrant children sent to correctional homes have to encounter numerous psychological disorders. Aim: The motive of the study is to explore the level of awareness, availability of services, stigma and obstacles to seeking assistance. Method: Due to the open-ended interview questions and a small sample size of 15 respondents, this study employed a qualitative methodology - a thematic analysis was done. Results: The findings revealed that, although the stigma is not publicly acknowledged, children who break the law and seek mental health services (MHS) are stigmatised. It was also shown that minor offenders fear that when they receive services provided by the staff of the observation home (OH), there will be a violation of their privacy and fear unforeseen repercussions. Conclusion: Collaborative action must proactively raise appropriate awareness to lessen the stigma linked with mental health problems, especially regarding MHS among these teenagers.

6.
Front Genet ; 13: 891055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035163

RESUMO

Chronic kidney disease (CKD) is defined as a persistent abnormality in the structure and function of kidneys and leads to high morbidity and mortality in individuals across the world. Globally, approximately 8%-16% of the population is affected by CKD. Proper screening, staging, diagnosis, and the appropriate management of CKD by primary care clinicians are essential in preventing the adverse outcomes associated with CKD worldwide. In light of this, the identification of biomarkers for the appropriate management of CKD is urgently required. Growing evidence has suggested the role of mRNAs and microRNAs in CKD, however, the gene expression profile of CKD is presently uncertain. The present study aimed to identify diagnostic biomarkers and therapeutic targets for patients with CKD. The human microarray profile datasets, consisting of normal samples and treated samples were analyzed thoroughly to unveil the differentially expressed genes (DEGs). After selection, the interrelationship among DEGs was carried out to identify the overlapping DEGs, which were visualized using the Cytoscape program. Furthermore, the PPI network was constructed from the String database using the selected DEGs. Then, from the PPI network, significant modules and sub-networks were extracted by applying the different centralities methods (closeness, betweenness, stress, etc.) using MCODE, Cytohubba, and Centiserver. After sub-network analysis we identified six overlapped hub genes (RPS5, RPL37A, RPLP0, CXCL8, HLA-A, and ANXA1). Additionally, the enrichment analysis was undertaken on hub genes to determine their significant functions. Furthermore, these six genes were used to find their associated miRNAs and targeted drugs. Finally, two genes CXCL8 and HLA-A were common for Ribavirin drug (the gene-drug interaction), after docking studies HLA-A was selected for further investigation. To conclude our findings, we can say that the identified hub genes and their related miRNAs can serve as potential diagnostic biomarkers and therapeutic targets for CKD treatment strategies.

7.
Genes (Basel) ; 13(7)2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35885958

RESUMO

Lung cancer is the major cause of cancer-associated deaths across the world in both men and women. Lung cancer consists of two major clinicopathological categories, i.e., small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Lack of diagnosis of NSCLC at an early stage in addition to poor prognosis results in ineffective treatment, thus, biomarkers for appropriate diagnosis and exact prognosis of NSCLC need urgent attention. The proposed study aimed to reveal essential microRNAs (miRNAs) involved in the carcinogenesis of NSCLC that probably could act as potential biomarkers. The NSCLC-associated expression datasets revealed 12 differentially expressed miRNAs (DEMs). MiRNA-mRNA network identified key miRNAs and their associated genes, for which functional enrichment analysis was applied. Further, survival and validation analysis for key genes was performed and consequently transcription factors (TFs) were predicted. We obtained twelve miRNAs as common DEMs after assessment of all datasets. Further, four key miRNAs and nine key genes were extracted from significant modules based on the centrality approach. The key genes and miRNAs reported in our study might provide some information for potential biomarkers profitable to increased prognosis and diagnosis of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo
8.
Genes (Basel) ; 13(2)2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35205254

RESUMO

Sepsis is a clinical syndrome with high mortality and morbidity rates. In sepsis, the abrupt release of cytokines by the innate immune system may cause multiorgan failure, leading to septic shock and associated complications. In the presence of a number of systemic disorders, such as sepsis, infections, diabetes, and systemic lupus erythematosus (SLE), cardiorenal syndrome (CRS) type 5 is defined by concomitant cardiac and renal dysfunctions Thus, our study suggests that certain mRNAs and unexplored pathways may pave a way to unravel critical therapeutic targets in three debilitating and interrelated illnesses, namely, sepsis, SLE, and CRS. Sepsis, SLE, and CRS are closely interrelated complex diseases likely sharing an overlapping pathogenesis caused by erroneous gene network activities. We sought to identify the shared gene networks and the key genes for sepsis, SLE, and CRS by completing an integrative analysis. Initially, 868 DEGs were identified in 16 GSE datasets. Based on degree centrality, 27 hub genes were revealed. The gProfiler webtool was used to perform functional annotations and enriched molecular pathway analyses. Finally, core hub genes (EGR1, MMP9, and CD44) were validated using RT-PCR analysis. Our comprehensive multiplex network approach to hub gene discovery is effective, as evidenced by the findings. This work provides a novel research path for a new research direction in multi-omics biological data analysis.


Assuntos
Lúpus Eritematoso Sistêmico , Sepse , Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Lúpus Eritematoso Sistêmico/genética , Sepse/genética
9.
J Asthma Allergy ; 15: 1-12, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35018101

RESUMO

Chronic rhinosinusitis (CRS) is defined as the inflammation of nose and paranasal sinuses, affecting the patients' quality of life and productivity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a principal clinical entity confirmed by the existence of chronic sinonasal inflammation and is characterized by anterior or posterior rhinorrhea, nasal congestion, hyposmia and/or facial pressure or facial pain. Several epidemiologic studies have revealed wide variations in the incidence of CRS among regions globally ranging from 4.6% to 12%. The Gulf countries are also witnessing an unprecedented burden of CRSwNP. According to the current clinical guidelines, glucocorticosteroids and antibiotics are the principal pharmacotherapeutic approaches. Endoscopic sinus surgery is recommended for those who have failed maximal pharmacotherapy. Recently, biologics are considered as an alternative best approach due to the complications associated with medical therapy and surgery. However, precise data on the clinical position of biologic agents in the management of CRSwNP in the Gulf region is not available. The present review article addresses the current diagnostic and management approaches for CRSwNP and also emphasizes the role of emerging biologics in the current treatment strategies for CRSwNP in the Gulf region. Further, a consensus protocol was convened to rationalize the guideline recommendations, strategize the best practices with biologics, and develop clinical practice guidelines for all primary-care specialists in the Gulf region. The consensus-based report will be a useful reference tool for primary-care physicians in primary-healthcare settings, regarding the appropriate time for the initiation of biological treatment in the Gulf region.

10.
Sci Rep ; 12(1): 1236, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35075176

RESUMO

Sarcoidosis is a multi-organ disorder where immunology, genetic and environmental factors play a key role in causing Sarcoidosis, but its molecular mechanism remains unclear. Identification of its genetics profiling that regulates the Sarcoidosis network will be one of the main challenges to understand its aetiology. We have identified differentially expressed genes (DEGs) by analyzing the gene expression profiling of Sarcoidosis and compared it with healthy control. Gene set enrichment analysis showed that these DEGs were mainly enriched in the inflammatory response, immune system, and pathways in cancer. Sarcoidosis protein interaction network was constructed by a total of 877 DEGs (up-down) and calculated its network topological properties, which follow hierarchical scale-free fractal nature up to six levels of the organization. We identified a large number of leading hubs that contain six key regulators (KRs) including ICOS, CTLA4, FLT3LG, CD33, GPR29 and ITGA4 are deeply rooted in the network from top to bottom, considering a backbone of the network. We identified the transcriptional factors (TFs) which are closely interacted with KRs. These genes and their TFs regulating the Sarcoidosis network are expected to be the main target for the therapeutic approaches and potential biomarkers. However, experimental validations of KRs needed to confirm their efficacy.


Assuntos
Sarcoidose/genética , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas , Sarcoidose/metabolismo
11.
Environ Sci Pollut Res Int ; 29(17): 25112-25137, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34837616

RESUMO

In Saudi Arabia, identifying homogenous zones based on rainfall patterns is critical for ensuring a predictable and stable water resource and agriculture management strategy. As a result, the present research aims to identify Saudi Arabia's homogeneous rainfall zones and examine rainfall patterns in these areas. By proposing a novel trend analysis technique with a particular graphical representation, this study utilises and compares the traditional Mann-Kendall (MK) test, modified MK test, and basic Sen-innovative trend analysis (ITA) method. Another approach is to use the Pettit change point test to objectively identify subcategories as "low" or "high." The applications are based on 40-year rainfall records from 22 Saudi Arabian meteorological sites. K-means clustering and hierarchical clustering on principle component analysis (HCPC) were used to find homogeneous areas. The results of the homogeneous region identification revealed that the research area is divided into three clusters, each with three distinct climatic characteristics. Cluster 1 contains eight stations, whereas clusters 2 and 3 each have seven. The results of trend identification utilising the MK, MMK, and ITA tests revealed that cluster 1 had a falling rainfall trend, whereas cluster 2 had a very minor decreasing and increasing rainfall trend. Cluster 2 can be thought of as a transition zone. Cluster 3 observed an upward trend in rainfall. While the proposed new form of ITA produced similar results with more detailed analysis such as change point-based high and low value identification, and magnitude of decreasing and increasing trend, the proposed new form of ITA produced similar results with more detailed analysis such as change point-based high and low value identification. This study will serve as a foundation for future work by scientists and planners on the identification of climatic zones, the development of trend detection techniques, and the formulation of water resource management strategies.


Assuntos
Agricultura , Meteorologia , Arábia Saudita
12.
Bioinformation ; 17(1): 86-100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393423

RESUMO

Cardio-renal syndrome (CRS) is a rapidly recognized clinical entity which refers to the inextricably connection between heart and renal impairment, whereby abnormality to one organ directly promotes deterioration of the other one. Biological markers help to gain insight into the pathological processes for early diagnosis with higher accuracy of CRS using known clinical findings. Therefore, it is of interest to identify target genes in associated pathways implicated linked to CRS. Hence, 119 CRS genes were extracted from the literature to construct the PPIN network. We used the MCODE tool to generate modules from network so as to select the top 10 modules from 23 available modules. The modules were further analyzed to identify 12 essential genes in the network. These biomarkers are potential emerging tools for understanding the pathophysiologic mechanisms for the early diagnosis of CRS. Ontological analysis shows that they are rich in MF protease binding and endo-peptidase inhibitor activity. Thus, this data help increase our knowledge on CRS to improve clinical management of the disease.

13.
Bioinform Biol Insights ; 15: 11779322211027396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276211

RESUMO

Cardiorenal syndromes constellate primary dysfunction of either heart or kidney whereby one organ dysfunction leads to the dysfunction of another. The role of several microRNAs (miRNAs) has been implicated in number of diseases, including hypertension, heart failure, and kidney diseases. Wide range of miRNAs has been identified as ideal candidate biomarkers due to their stable expression. Current study was aimed to identify crucial miRNAs and their target genes associated with cardiorenal syndrome and to explore their interaction analysis. Three differentially expressed microRNAs (DEMs), namely, hsa-miR-4476, hsa-miR-345-3p, and hsa-miR-371a-5p, were obtained from GSE89699 and GSE87885 microRNA data sets, using R/GEO2R tools. Furthermore, literature mining resulted in the retrieval of 15 miRNAs from scientific research and review articles. The miRNAs-gene networks were constructed using miRNet (a Web platform of miRNA-centric network visual analytics). CytoHubba (Cytoscape plugin) was adopted to identify the modules and the top-ranked nodes in the network based on Degree centrality, Closeness centrality, Betweenness centrality, and Stress centrality. The overlapped miRNAs were further used in pathway enrichment analysis. We found that hsa-miR-21-5p was common in 8 pathways out of the top 10. Based on the degree, 5 miRNAs, namely, hsa-mir-122-5p, hsa-mir-222-3p, hsa-mir-21-5p, hsa-mir-146a-5p, and hsa-mir-29b-3p, are considered as key influencing nodes in a network. We suggest that the identified miRNAs and their target genes may have pathological relevance in cardiorenal syndrome (CRS) and may emerge as potential diagnostic biomarkers.

14.
Data Brief ; 35: 106945, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33763511

RESUMO

Data was collected on the quality and quantity of wastewater discharged from different petroleum and nonpetroleum industrial sources in Kuwait over a period of one year. A field survey included 75 factories distributed in three industrial areas (Sabhan, Kuwait City, and Shuaiba). Among the industries contacted only 41 agreed to participate in field measurements and wastewater sampling campaign. The questionnaire feedback obtained indicated that the activities of these industries can be categorized into 20 categories including 4 and 37 petroleum and nonpetroleum industries, respectively. The mean quality of wastewater generated in Sabhan industrial area were found to be higher than those of Kuwait City and Shuaiba areas. The inorganic results indicated that high values of total suspended solids (TSS), total dissolved solids (TDS), sulfide, free chlorine, and fluoride were observed in the wastewater of petroleum factories of Shuaiba, while high values of total phosphate, ammonia, total Kjeldahl nitrogen, total nitrogen, and floatables were observed in the wastewater of nonpetroleum factories of Kuwait City. Additionally, organic results indicated that high values of chemical oxygen demand (COD), biochemical oxygen demand (BOD), oil and grease, and total petroleum hydrocarbons (TPHs) were observed in the wastewater of petroleum factories of Shuaiba area. GIS maps were generated for 25 wastewater parameters for the participating 41 factories using ArcView GIS software.

16.
Front Cardiovasc Med ; 8: 755321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35071341

RESUMO

In fact, the risk of dying from CVD is significant when compared to the risk of developing end-stage renal disease (ESRD). Moreover, patients with severe CKD are often excluded from randomized controlled trials, making evidence-based therapy of comorbidities like CVD complicated. Thus, the goal of this study was to use an integrated bioinformatics approach to not only uncover Differentially Expressed Genes (DEGs), their associated functions, and pathways but also give a glimpse of how these two conditions are related at the molecular level. We started with GEO2R/R program (version 3.6.3, 64 bit) to get DEGs by comparing gene expression microarray data from CVD and CKD. Thereafter, the online STRING version 11.1 program was used to look for any correlations between all these common and/or overlapping DEGs, and the results were visualized using Cytoscape (version 3.8.0). Further, we used MCODE, a cytoscape plugin, and identified a total of 15 modules/clusters of the primary network. Interestingly, 10 of these modules contained our genes of interest (key genes). Out of these 10 modules that consist of 19 key genes (11 downregulated and 8 up-regulated), Module 1 (RPL13, RPLP0, RPS24, and RPS2) and module 5 (MYC, COX7B, and SOCS3) had the highest number of these genes. Then we used ClueGO to add a layer of GO terms with pathways to get a functionally ordered network. Finally, to identify the most influential nodes, we employed a novel technique called Integrated Value of Influence (IVI) by combining the network's most critical topological attributes. This method suggests that the nodes with many connections (calculated by hubness score) and high spreading potential (the spreader nodes are intended to have the most impact on the information flow in the network) are the most influential or essential nodes in a network. Thus, based on IVI values, hubness score, and spreading score, top 20 nodes were extracted, in which RPS27A non-seed gene and RPS2, a seed gene, came out to be the important node in the network.

17.
Infect Genet Evol ; 87: 104649, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271338

RESUMO

Tuberculosis (TB) is one of the deadliest diseases since ancient times and is still a global health problem. So, there is a need to develop new approaches for early detection of TB and understand the host-pathogen relationship. In the present study, we have analyzed microarray data sets and compared the transcriptome profiling of the healthy individual with latent infection (LTBI) and active TB (TB) patients, and identified the differentially expressed genes (DEGs). Next, we performed the systematic network meta-analysis of the DEGs, which identified the seven most influencing hub genes (IL6, IL1B, TNF, NFKB1, STAT1, JAK2, and MAPK8) as the potential therapeutic target in the tuberculosis disease. These target genes are involved in many biological processes like cell cycle control, apoptosis, complement signalling, enhanced cytokine & chemokine signalling, pro-inflammatory responses, and host immune responses. Additionally, we also identified 22 inferred genes that are mainly engaged in the induction of innate immune response, cellular response to interleukin-6, inflammatory response, apoptotic process, I-kappaB-phosphorylation, JAK-STAT signalling pathway, macrophage activation, cell growth, and cell signalling. The proper attention of these inferred genes may open up a new horizon to understand the defensive mechanisms of TB disease. The transcriptome profiling and network approach can enhance the understanding of the molecular pathogenesis of tuberculosis infection and have implications for the plan and execution of mRNA expression tools to support early diagnostics and treatment of Mycobacterium tuberculosis (M.tb).


Assuntos
Antituberculosos/uso terapêutico , Genes Bacterianos , Variação Genética , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Biomarcadores , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Metanálise em Rede , Análise Serial de Proteínas , Transcriptoma
18.
Genes (Basel) ; 11(11)2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182754

RESUMO

Sepsis is a dysregulated immune response disease affecting millions worldwide. Delayed diagnosis, poor prognosis, and disease heterogeneity make its treatment ineffective. miRNAs are imposingly involved in personalized medicine such as therapeutics, due to their high sensitivity and accuracy. Our study aimed to reveal the biomarkers that may be involved in the dysregulated immune response in sepsis and lung injury using a computational approach and in vivo validation studies. A sepsis miRNA Gene Expression Omnibus (GEO) dataset based on the former analysis of blood samples was used to identify differentially expressed miRNAs (DEMs) and associated hub genes. Sepsis-associated genes from the Comparative Toxicogenomics Database (CTD) that overlapped with identified DEM targets were utilized for network construction. In total, 317 genes were found to be regulated by 10 DEMs (three upregulated, namely miR-4634, miR-4638-5p, and miR-4769-5p, and seven downregulated, namely miR-4299, miR-451a, miR181a-2-3p, miR-16-5p, miR-5704, miR-144-3p, and miR-1290). Overall hub genes (HIP1, GJC1, MDM4, IL6R, and ERC1) and for miR-16-5p (SYNRG, TNRC6B, and LAMTOR3) were identified based on centrality measures (degree, betweenness, and closeness). In vivo validation of miRNAs in lung tissue showed significantly downregulated expression of miR-16-5p corroborating with our computational findings, whereas expression of miR-181a-2-3p and miR-451a were found to be upregulated in contrast to the computational approach. In conclusion, the differential expression pattern of miRNAs and hub genes reported in this study may help to unravel many unexplored regulatory pathways, leading to the identification of critical molecular targets for increased prognosis, diagnosis, and drug efficacy in sepsis and associated organ injuries.


Assuntos
Lesão Pulmonar/genética , MicroRNAs/genética , Sepse/genética , Biomarcadores , Biologia Computacional/métodos , Bases de Dados Genéticas , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Prognóstico , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética
19.
Bioinformation ; 16(11): 910-922, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34803267

RESUMO

Parathyroid adenoma (PA) is marked by a certain benign outgrowth in the surface of parathyroid glands. The transcriptome analysis of parathyroid adenomas can provide a deep insight into actively expressed genes and transcripts. Hence, we analyzed and compared the gene expression profiles of parathyroid adenomas and healthy parathyroid gland tissues from Gene Expression Omnibus (GEO) database. We identified a total of 280 differentially expressed genes (196 up-regulated, 84 down-regulated), which are involved in a wide array of biological processes. We further constructed a gene interaction network and analyzed its topological properties to know the network structure and its hidden mechanism. This will help to understand the molecular mechanisms underlying parathyroid adenoma development. We thus identified 13 key regulators (PRPF19, SMC3, POSTN, SNIP1, EBF1, MEIS2, PAX9, SCUBE2, WNT4, ARHGAP10, DOCK5, CAV1 and VSIR), which are deep-rooted from top to bottom in the gene interaction network forming a backbone for the network. The structural features of the network are probably maintained by crosstalk between important genes within the network along with associated functional modules.Thus, gene-expression profiling and network approach could be used to provide an independent platform to glen insights from available clinical data.

20.
Front Genet ; 10: 932, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749827

RESUMO

Tuberculosis (TB) is one of deadly transmissible disease that causes death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease, indicating that host genetic factors may play key role in determining susceptibility to TB disease. In this way, the analysis of gene expression profiling of TB infected individuals can give us a snapshot of actively expressed genes and transcripts under various conditions. In the present study, we have analyzed microarray data set and compared the gene expression profiles of patients with different datasets of healthy control, latent infection, and active TB. We observed the transition of genes from normal condition to different stages of the TB and identified and annotated those genes/pathways/processes that have important roles in TB disease during its cyclic interventions in the human body. We identified 488 genes that were differentially expressed at various stages of TB and allocated to pathways and gene set enrichment analysis. These pathways as well as GSEA's importance were evaluated according to the number of DEGs presents in both. In addition, we studied the gene regulatory networks that may help to further understand the molecular mechanism of immune response against the TB infection and provide us a new angle for future biomarker and therapeutic targets. In this study, we identified 26 leading hubs which are deeply rooted from top to bottom in the gene regulatory network and work as the backbone of the network. These leading hubs contains 31 key regulator genes, of which 14 genes were up-regulated and 17 genes were down-regulated. The proposed approach is based on gene-expression profiling, and network analysis approaches predict some unknown TB-associated genes, which can be considered (or can be tested) as reliable candidates for further (in vivo/in vitro) studies.

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