scholarly journals Collateral sensitivity to β-lactam drugs in drug-resistant tuberculosis is driven by the transcriptional wiring of BlaI operon genes

2017 ◽  
Author(s):  
AS Trigos ◽  
BW Goudey ◽  
J Bedő ◽  
TC Conway ◽  
NG Faux ◽  
...  
Keyword(s):  
Low Cost ◽  
Tuberculosis Treatment ◽  
Global Public Health ◽  
Intrinsic Resistance ◽  
Protein Protein Interaction ◽  
Collateral Sensitivity ◽  
Network Analyses ◽  
Enhanced Sensitivity ◽  
Collateral Consequence ◽  
Evolution Of Resistance

AbstractBackground:The evolution and spread of antimicrobial resistance is a major global public health threat. In some cases the evolution of resistance to one antimicrobial seemingly results in enhanced sensitivity to another (known as ‘collateral sensitivity’). This largely underexplored phenomenon represents a fascinating evolutionary paradigm that opens new therapeutic possibilities for patients infected with pathogens unresponsive to classical treatments. Intrinsic resistance to β-lactams in Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis) has traditionally curtailed the use of these low-cost and easy-to-administer drugs for tuberculosis treatment. Recently, β-lactam sensitivity has been reported in strains resistant to classical tuberculosis drug therapy, leading to a resurgence of interest in using β-lactams in the clinic. Unfortunately though, there remains a limited understanding of the mechanisms driving β-lactam sensitivity.Methods:We used a novel combination of systems biology and computational approaches to characterize the molecular underpinnings of β-lactam sensitivity in Mtb. We performed differential gene expression and coexpression analyses of genes previously associated with β-lactam sensitivity and genes associated with resistance to classical tuberculosis drugs. Protein-protein interaction and gene regulatory network analyses were used to validate regulatory interactions between these genes, and random walks through the networks identified key mediators of these interactions. Further validation was obtained using functional in silico knockout of gene pairs.Results:Our results reveal up regulation of the key regulatory inhibitor of β-lactamase production, blal, following treatment with classical drugs. Co-expression and network analyses showed direct co-regulation between genes associated with β-lactam sensitivity and those associated with resistance to classical tuberculosis treatment. blal and its downstream genes (sigC and atpH) were found to be key mediators of these interactions.Conclusions:Our results support the hypothesis that Mtb β-lactam sensitivity is a collateral consequence of the evolution of resistance to classical tuberculosis drugs, mediated through changes to transcriptional regulation. These findings support continued exploration of β-lactams for the treatment of tuberculosis, particularly for patients infected with strains resistant to classical therapies that are otherwise difficult to treat. Importantly, this work also highlights the potential of systems-level and network biology approaches to improve our understanding of collateral drug sensitivity.

scholarly journals Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Miao Xu ◽  
Tianxiang Ouyang ◽  
Kaiyang Lv ◽  
Xiaorong Ma
Keyword(s):  
Differential Expression ◽  
Enrichment Analysis ◽  
Infantile Hemangioma ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Normal Tissues ◽  
Network Analyses ◽  
Cycle Arrest ◽  
Auc Value

BackgroundInfantile hemangioma (IH) is characterized by proliferation and regression.MethodsBased on the GSE127487 dataset, the differentially expressed genes (DEGs) between 6, 12, or 24 months and normal samples were screened, respectively. STEM software was used to screen the continued up-regulated or down-regulated in common genes. The modules were assessed by weighted gene co-expression network analysis (WGCNA). The enrichment analysis was performed to identified the biological function of important module genes. The area under curve (AUC) value and protein-protein interaction (PPI) network were used to identify hub genes. The differential expression of hub genes in IH and normal tissues was detected by qPCR.ResultsThere were 5,785, 4,712, and 2,149 DEGs between 6, 12, and 24 months and normal tissues. We found 1,218 DEGs were up-regulated or down-regulated expression simultaneously in common genes. They were identified as 10 co-expression modules. Module 3 and module 4 were positively or negatively correlated with the development of IH, respectively. These two module genes were significantly involved in immunity, cell cycle arrest and mTOR signaling pathway. The two module genes with AUC greater than 0.8 at different stages of IH were put into PPI network, and five genes with the highest degree were identified as hub genes. The differential expression of these genes was also verified by qRTPCR.ConclusionFive hub genes may distinguish for proliferative and regressive IH lesions. The WGCNA and PPI network analyses may help to clarify the molecular mechanism of IH at different stages.

scholarly journals Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis

2018 ◽  
Author(s):  
Md. Rezanur Rahman ◽  
Tania Islam ◽  
Esra Gov ◽  
Beste Turanli ◽  
Md. Shahjaman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Repositioning ◽  
Molecular Biomarker ◽  
Cell Cycles ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Network Analyses ◽  
Microarray Datasets ◽  
Prognostic Power ◽  
Hub Proteins

Background and objectives: Colorectal cancer (CRC) is the 2nd most cause of cancer related death in the world, but early diagnosis ameliorates the survival of CRC. This report directed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed two microarray datasets (GSE35279 and GSE21815) to identify common differentially expressed genes (DEGs). We performed functional overrepresentation, pathway enrichment, protein-protein interaction (PPI), reporter biomolecules, survival, and drug repositioning analyses were done on common DEGs. Results: Total 727 up-regulated and 99 down-regulated DEGs were detected. The significantly enriched pathways PI3K-Akt signaling, Wnt signaling, ECM-interaction, cell cycles were identified. The 10 hub proteins (ADNP, CCND1, CD44, CDK4, CEBPB, CENPA, CENPH, CENPN, MYC, and RFC2) were selected as proteomic signatures from PPI network. Analyses revealed 10 reporter transcription factors (ETS1, ESR1, GATA1, GATA2, GATA3, AR, YBX1, FOXP3, E2F4, and PRDM14) and 2 reporter microRNAs (miR-193b-3p and miR-615-3p) as regulatory component. The prognostic power analysis revealed that hub proteins and reporter biomolecules related with worse survival of patients in CRC. Several candidate repositioned drugs including anti-neoplastic and immunomodulating agents were identified using Connectivity map (CMap) and geneXpharma tool. Conclusions: This study presents biomarker signatures at protein and RNA levels with prognostic capability in CRC. We think that the molecular signatures and candidate drugs presented in this study can be potential biomarkers and therapeutic target in CRC.

scholarly journals Analysis of Cadmium and Lead in honey: direct-determination by Graphite Furnace Atomic Absorption Spectrometry

ACTA IMEKO ◽  
2016 ◽  
Vol 5 (1) ◽  
pp. 10 ◽  
Author(s):  
Andrea Colabucci ◽  
Anna Chiara Turco ◽  
Maria Ciprotti ◽  
Marco Di Gregorio ◽  
Angela Sorbo ◽  
...  
Keyword(s):  
Atomic Absorption Spectrometry ◽  
Atomic Absorption ◽  
Graphite Furnace ◽  
Low Cost ◽  
Direct Determination ◽  
Absorption Spectrometry ◽  
Time Saving ◽  
Microwave Sample Preparation ◽  
Network Analyses ◽  
Graphite Furnace Atomic Absorption

<p>One of the emerging issues regarding the analysis of inorganic contaminants in food is the determination of Cadmium (Cd) and Lead (Pb) in honey. In fact, this kind of analysis is foreseen in most of the National Residue Control Plans (NRCPs) that European Union Member States (EU MSs) have to perform according to Directive 96/23.</p><p>With the aim to provide technical support to the EU National Reference Laboratories (NRLs), an easy-to-use method on direct determination (DD) of Cd and Pb in honey by graphite furnace atomic absorption spectrometry (GF-AAS) after dissolution in an aqueous mixture of 2.5 % HNO<sub>3</sub> (v/v) and 12.5 % H<sub>2</sub>O<sub>2</sub> (v/v) was in-house validated and distributed to the NRLs network. Analyses were carried out on a batch prepared for the feasibility study of the EURL-CEFAO 19<sup>th</sup> PT on honey. The validation levels (20 and 100 µg/kg for Cd and Pb, respectively) were chosen similar to those that would have been proposed for the PT.</p><p>The method proved its efficacy in terms of analytical performance; it appears to be low cost and time saving compared to a microwave sample preparation. In addition, it also decreases the environmental impact, being the amount of acid and reagents considerably reduced.  </p>

scholarly journals Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Giuseppe Gianini Figueirêdo Leite ◽  
Bianca Lima Ferreira ◽  
Alexandre Keiji Tashima ◽  
Erika Sayuri Nishiduka ◽  
Edecio Cunha-Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Interaction Network ◽  
Low Density ◽  
Mitochondrial Translation ◽  
Peripheral Blood Mononuclear ◽  
Protein Coding ◽  
Protein Protein Interaction ◽  
Network Analyses ◽  
Host Defense System

Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in “omics” technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co‐differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down‐regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up‐regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host‐defense system.

scholarly journals EGFET-Based Sensors for Bioanalytical Applications: A Review

Sensors ◽  
2018 ◽  
Vol 18 (11) ◽  
pp. 4042 ◽  
Author(s):  
Salvatore Pullano ◽  
Costantino Critello ◽  
Ifana Mahbub ◽  
Nishat Tasneem ◽  
Samira Shamsir ◽  
...  
Keyword(s):  
Field Effect ◽  
Field Effect Transistor ◽  
Low Cost ◽  
High Sensitivity ◽  
Nucleic Acid Hybridization ◽  
Protein Protein Interaction ◽  
Effect Transistor ◽  
Bioanalytical Applications ◽  
Antigen Antibody ◽  
Low Cost Manufacturing

Since the 1970s, a great deal of attention has been paid to the development of semiconductor-based biosensors because of the numerous advantages they offer, including high sensitivity, faster response time, miniaturization, and low-cost manufacturing for quick biospecific analysis with reusable features. Commercial biosensors have become highly desirable in the fields of medicine, food, and environmental monitoring as well as military applications, whereas increasing concerns about food safety and health issues have resulted in the introduction of novel legislative standards for these sensors. Numerous devices have been developed for monitoring biological processes such as nucleic acid hybridization, protein–protein interaction, antigen–antibody bonds, and substrate–enzyme reactions, just to name a few. Since the 1980s, scientific interest moved to the development of semiconductor-based devices, which also include integrated front-end electronics, such as the extended-gate field-effect transistor (EGFET) biosensor, one of the first miniaturized chemical sensors. This work is intended to be a review of the state of the art focused on the development of biosensors and chemosensors based on extended-gate field-effect transistor within the field of bioanalytical applications, which will highlight the most recent research reported in the literature. Moreover, a comparison among the diverse EGFET devices will be presented, giving particular attention to the materials and technologies.

scholarly journals An integrative methodology based on protein-protein interaction networks for identification and functional annotation of disease-relevant genes applied to channelopathies

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Milagros Marín ◽  
Francisco J. Esteban ◽  
Hilario Ramírez-Rodrigo ◽  
Eduardo Ros ◽  
María José Sáez-Lara
Keyword(s):  
Protein Interaction ◽  
Clinical Manifestations ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Centrality Measures ◽  
Protein Protein Interaction ◽  
Network Analyses ◽  
Complex Group ◽  
Heterogeneous Datasets ◽  
Protein Protein Interaction Networks

Abstract Background Biologically data-driven networks have become powerful analytical tools that handle massive, heterogeneous datasets generated from biomedical fields. Protein-protein interaction networks can identify the most relevant structures directly tied to biological functions. Functional enrichments can then be performed based on these structural aspects of gene relationships for the study of channelopathies. Channelopathies refer to a complex group of disorders resulting from dysfunctional ion channels with distinct polygenic manifestations. This study presents a semi-automatic workflow using protein-protein interaction networks that can identify the most relevant genes and their biological processes and pathways in channelopathies to better understand their etiopathogenesis. In addition, the clinical manifestations that are strongly associated with these genes are also identified as the most characteristic in this complex group of diseases. Results In particular, a set of nine representative disease-related genes was detected, these being the most significant genes in relation to their roles in channelopathies. In this way we attested the implication of some voltage-gated sodium (SCN1A, SCN2A, SCN4A, SCN4B, SCN5A, SCN9A) and potassium (KCNQ2, KCNH2) channels in cardiovascular diseases, epilepsies, febrile seizures, headache disorders, neuromuscular, neurodegenerative diseases or neurobehavioral manifestations. We also revealed the role of Ankyrin-G (ANK3) in the neurodegenerative and neurobehavioral disorders as well as the implication of these genes in other systems, such as the immunological or endocrine systems. Conclusions This research provides a systems biology approach to extract information from interaction networks of gene expression. We show how large-scale computational integration of heterogeneous datasets, PPI network analyses, functional databases and published literature may support the detection and assessment of possible potential therapeutic targets in the disease. Applying our workflow makes it feasible to spot the most relevant genes and unknown relationships in channelopathies and shows its potential as a first-step approach to identify both genes and functional interactions in clinical-knowledge scenarios of target diseases. Methods An initial gene pool is previously defined by searching general databases under a specific semantic framework. From the resulting interaction network, a subset of genes are identified as the most relevant through the workflow that includes centrality measures and other filtering and enrichment databases.

Examination of the impacts of e-cigarettes smoking on the tobacco non-smokers

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Tha’er Kanaan ◽  
Nayef Alkhrasha ◽  
Mahmoud Al-Masaeed
Keyword(s):  
Public Health ◽  
Keyword Search ◽  
Low Cost ◽  
Google Scholar ◽  
Health Concern ◽  
Second Hand Smoke ◽  
Search Process ◽  
Global Public Health ◽  
The Public ◽  
Health Related

Significance and Aim: The effects of cigarettes smoking on both smokers and non-smoker have been an issue of global public health concern. This led to the emergence of e-cigarettes as an alternative to help smokers in their smoking quitting journey. However, it has remained unclear on the public health costs this has on the non-smokers. The ILR Review is developed to examine the public health the use of e-cigarettes have on non-smokers. Methods: The ILR sourced data from four databases Scopus, Medline, CINAHL, and Google Scholar. This was through a keyword search process using the ‘e-cigarettes’ or ‘vaping’ AND ‘addiction’ AND ‘non-smokers’ AND ‘effects OR ‘consequences, search phrases. The search protocol was replicated for all the databases. The findings from the search process were Scopus (419), Medline (283), CINAHL (311), and Google Scholar (321). The ILR applied inclusion and exclusion criteria and the GRADE model to assess the quality of the articles. Consequently, only 23 articles remained for analysis and inclusion in the ILR findings. Finally, the articles were screed through the EQUATOR PRISMA tool and extracted in readiness for analysis. Findings and Analysis: The results demonstrate that the use of e-cigarettes has two leading public health implications on non-smokers, namely (i) the risk of new addictions and (ii) the risk of health-related illnesses. The findings affirm that the ease of accessing the e-cigarettes, the marketing craze, and the low cost of acquiring them has exposed a rising number of young people to its new addiction. The addiction could at times progress into tobacco smoking addiction. Secondly, the findings indicate that second hand smoke exposure, also known as passive smoking exposes the public to increased lung cancer, lung diseases and COPD illnesses. Conclusion: The ILR concludes that e-cigarettes have far-reaching public health concerns on non-smokers. This necessitates the need for increased restrictions and control on the e-cigarettes access and availability. This is in addition to enacting strict regulations on smoking areas and freedom.

scholarly journals Mechanism Analysis of Coix Seed in Gastric Cancer Treatment Based on Biological Network Modules

2020 ◽  
Vol 15 (5) ◽  
pp. 1934578X2092752
Author(s):  
Fengbin Zhang ◽  
Xiaoyan Liu ◽  
Bingjie Huo ◽  
Bing Li ◽  
Ruixing Zhang
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Biological Network ◽  
Interaction Network ◽  
Mechanism Analysis ◽  
Protein Protein Interaction ◽  
Network Analyses ◽  
Analysis Methods ◽  
Coix Seed ◽  
Modular Analysis

Coix seed, the mature seed of Coix lacryma-jobi L., is a traditional herb widely used in various cancer adjuvant treatments; however, its mechanism is unknown. The aim of this study was to reveal the multitarget mechanisms of Coix seed in the treatment of gastric cancer (GC) by biological network and modular analysis methods. Forty-one ingredients and 482 targets of Coix seed and 165 GC-related genes were obtained from databases. Twelve on-target genes ( AICDA, CASP3, EP300, ERBB2, FGFR2, IL12A, IL12B, IL1B, LOX, TJP1, TP53, and TRIB3) of Coix seed overlapped with GC-related genes. Using compound-target and protein–protein interaction network analyses, we discovered the core targets of Coix seed. Markov cluster algorithm-based modular analysis identified 5 potential module targets of Coix seed for GC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated the vast actions of Coix seed, which involve pathways in cancer, the cell cycle, receptor signal transduction, deoxyribonucleic acid damage response, transcriptional regulation, apoptosis, and cell connections. This study elucidated the potential mechanisms of Coix seed on GC, which may lead to the development of an effective drug. Additionally, this study showed the feasibility of network and modular analysis methods to investigate traditional Chinese medicinal herbal mechanisms and may provide a new angle for further research in the field of anticancer mechanisms and multitarget drugs.

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