scholarly journals Reducing the Search Space in Literature-Based Discovery by Exploring Outlier Documents: a Case Study in Finding Links Between Gut Microbiome and Alzheimer’s Disease

2017 ◽  
Vol 3 (3) ◽  
pp. 58 ◽  
Author(s):  
Bojan Cestnik ◽  
Elsa Fabbretti ◽  
Donatella Gubiani ◽  
Tanja Urbančič ◽  
Nada Lavrač

Literature-based discovery tools have been often used to overcome the problem of fragmentation of science and to assist researchers in their process of cross-domain knowledge discovery. In this paper we propose a methodology for cross-domain literature-based discovery that focuses on outlier documents to reduce the search space of potential cross-domain links and to improve search efficiency. In a previous study, literature mining tools OntoGen for document clustering and CrossBee for cross-domain bridging term exploration were combined to search for hidden relations in scientific papers from two different domains of interest, where the utility of the approach was demonstrated in a study involving PubMed papers about Alzheimer’s disease and gut microbiome. This paper extends the approach by proposing a methodology, implemented as a repeatable workflow in a web-based text mining platform TextFlows, which enables easy access and execution of the methodology for the interested researcher.

2021 ◽  
Vol 9 (4) ◽  
pp. 815
Author(s):  
Malena dos Santos Guilherme ◽  
Vu Thu Thuy Nguyen ◽  
Christoph Reinhardt ◽  
Kristina Endres

The gut brain axis seems to modulate various psychiatric and neurological disorders such as Alzheimer’s disease (AD). Growing evidence has led to the assumption that the gut microbiome might contribute to or even present the nucleus of origin for these diseases. In this regard, modifiers of the microbial composition might provide attractive new therapeutics. Aim of our study was to elucidate the effect of a rigorously changed gut microbiome on pathological hallmarks of AD. 5xFAD model mice were treated by antibiotics or probiotics (L. acidophilus and L. rhamnosus) for 14 weeks. Pathogenesis was measured by nest building capability and plaque deposition. The gut microbiome was affected as expected: antibiotics significantly reduced viable commensals, while probiotics transiently increased Lactobacillaceae. Nesting score, however, was only improved in antibiotics-treated mice. These animals additionally displayed reduced plaque load in the hippocampus. While various physiological parameters were not affected, blood sugar was reduced and serum glucagon level significantly elevated in the antibiotics-treated animals together with a reduction in the receptor for advanced glycation end products RAGE—the inward transporter of Aβ peptides of the brain. Assumedly, the beneficial effect of the antibiotics was based on their anti-diabetic potential.


2020 ◽  
Author(s):  
Jarmila Nahálková

AbstractSIRT3 is the mitochondrial protein lysine deacetylase with a prominent role in the maintenance of mitochondrial integrity vulnerable in the range of diseases. The present study examines the SIRT3 substrate interaction network for the identification of its biological functions in the cellular anti-aging mechanisms. The pathway enrichment, the protein function prediction, and the protein node prioritization analysis were performed based on 407 SIRT3 substrates, which were collected by the data mining. The substrates are interlinked by 1230 direct protein-protein interactions included in the GeneMania database. The analysis of the SIRT3 substrate interaction network highlighted Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and non-alcoholic fatty liver disease (NAFLD) as the most associated with SIRT3 lysine deacetylase activity. The most important biological functions of SIRT3 substrates are within the respiratory electron transport chain, tricarboxylic acid cycle and fatty acid, triacylglycerol, and ketone body metabolism. In brown adipose tissue, SIRT3 activity contributes to the adaptive thermogenesis by the increase of energy production of the organisms. SIRT3 exhibits several modes of neuroprotective actions in the brain and liver including prevention of the mitochondrial damages due to the respiratory electron transfer chain failure, the quenching of ROS, the inhibition of the mitochondrial membrane potential loss, and the regulation of mitophagy. Related to its role in Alzheimer’s disease, SIRT3 activation performs as a repressor of BACE1 through SIRT3-LKB1-AMPK-CREB-PGC-1α-PPARG-BACE1 (SIRT3-BACE1) pathway, which was created based on the literature mining and by employing Wikipathways application. The pathway enrichment analysis of the extended interaction network of the SIRT3-BACE1 pathway nodes displayed the functional relation to the circadian clock, which also deteriorates during the progress of AD and it is the causative of AD, PD, and HD. The use of SIRT3 activators in combination with the stimulating effect of regular exercise is further discussed as an attractive option for the improvement of cognitive decline during aging and the progressive stages of neurodegeneration.


2022 ◽  
pp. 354-376
Author(s):  
Sourav Samanta ◽  
Madhu Ramesh ◽  
Ashish Kumar ◽  
Thimmaiah Govindaraju

2018 ◽  
Vol 55 (11) ◽  
pp. 8243-8250 ◽  
Author(s):  
Li Lin ◽  
Li Juan Zheng ◽  
Long Jiang Zhang

2018 ◽  
Vol 56 (3) ◽  
pp. 1841-1851 ◽  
Author(s):  
Marta Sochocka ◽  
Katarzyna Donskow-Łysoniewska ◽  
Breno Satler Diniz ◽  
Donata Kurpas ◽  
Ewa Brzozowska ◽  
...  

Author(s):  
Anderson Rossanez ◽  
Julio Cesar dos Reis ◽  
Ricardo da Silva Torres ◽  
Hélène de Ribaupierre

Abstract Background Knowledge is often produced from data generated in scientific investigations. An ever-growing number of scientific studies in several domains result into a massive amount of data, from which obtaining new knowledge requires computational help. For example, Alzheimer’s Disease, a life-threatening degenerative disease that is not yet curable. As the scientific community strives to better understand it and find a cure, great amounts of data have been generated, and new knowledge can be produced. A proper representation of such knowledge brings great benefits to researchers, to the scientific community, and consequently, to society. Methods In this article, we study and evaluate a semi-automatic method that generates knowledge graphs (KGs) from biomedical texts in the scientific literature. Our solution explores natural language processing techniques with the aim of extracting and representing scientific literature knowledge encoded in KGs. Our method links entities and relations represented in KGs to concepts from existing biomedical ontologies available on the Web. We demonstrate the effectiveness of our method by generating KGs from unstructured texts obtained from a set of abstracts taken from scientific papers on the Alzheimer’s Disease. We involve physicians to compare our extracted triples from their manual extraction via their analysis of the abstracts. The evaluation further concerned a qualitative analysis by the physicians of the generated KGs with our software tool. Results The experimental results indicate the quality of the generated KGs. The proposed method extracts a great amount of triples, showing the effectiveness of our rule-based method employed in the identification of relations in texts. In addition, ontology links are successfully obtained, which demonstrates the effectiveness of the ontology linking method proposed in this investigation. Conclusions We demonstrate that our proposal is effective on building ontology-linked KGs representing the knowledge obtained from biomedical scientific texts. Such representation can add value to the research in various domains, enabling researchers to compare the occurrence of concepts from different studies. The KGs generated may pave the way to potential proposal of new theories based on data analysis to advance the state of the art in their research domains.


Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 424 ◽  
Author(s):  
M. Mohajeri

In the last decade, the microbiome in general and the gut microbiome in particular have been associated not only to brain development and function, but also to the pathophysiology of brain aging and to neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, or multiple sclerosis (MS) [...]


2021 ◽  
Vol 12 ◽  
Author(s):  
Nesrine S. El Sayed ◽  
Esraa A. Kandil ◽  
Mamdooh H. Ghoneum

Sporadic Alzheimer’s disease (AD) is the most common neurodegenerative disorder with cognitive dysfunction. Remarkably, alteration in the gut microbiome and resultant insulin resistance has been shown to be connected to metabolic syndrome, the crucial risk factor for AD, and also to be implicated in AD pathogenesis. Thus, this study, we assessed the efficiency of probiotics fermentation technology (PFT), a kefir product, in enhancing insulin signaling via modulation of gut microbiota to halt the development of AD. We also compared its effectiveness to that of pioglitazone, an insulin sensitizer that has been confirmed to substantially treat AD. AD was induced in mice by a single injection of intracerebroventricular streptozotocin (STZ; 3 mg/kg). PFT (100, 200, 400 mg/kg) and pioglitazone (30 mg/kg) were administered orally for 3 weeks. Behavioral tests were conducted to assess cognitive function, and hippocampal levels of acetylcholine (Ach) and β-amyloid (Aβ1–42) protein were assessed along with histological examination. Moreover, the expression of the insulin receptor, insulin degrading enzyme (IDE), and the phosphorylated forms of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), mammalian target of rapamycin (mTOR), and tau were detected. Furthermore, oxidative stress and inflammatory biomarkers were estimated. Treatment with PFT reversed STZ-induced neurodegeneration and cognitive impairment, enhanced hippocampal Ach levels, and reduced Aβ1–42 levels after restoration of IDE activity. PFT also improved insulin signaling, as evidenced by upregulation of insulin receptor expression and activation of PI3K/Akt signaling with subsequent suppression of GSK-3β and mTOR signaling, which result in the downregulation of hyperphosphorylated tau. Moreover, PFT significantly diminished oxidative stress and inflammation induced by STZ. These potential effects were parallel to those produced by pioglitazone. Therefore, PFT targets multiple mechanisms incorporated in the pathogenesis of AD and hence might be a beneficial therapy for AD.


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