scholarly journals Developing Network-Based Systems Toxicology by Combining Transcriptomics Data with Literature Mining and Multiscale Quantitative Modeling

2018 ◽  
Author(s):  
Alain Sewer ◽  
Marja Talikka ◽  
Florian Martin ◽  
Julia Hoeng ◽  
Manuel C Peitsch
Keyword(s):  
Quantitative Modeling ◽  
Literature Mining ◽  
Systems Toxicology ◽  
Transcriptomics Data

scholarly journals A Systems Biology Approach Reveals the Dose- and Time-Dependent Effect of Primary Human Airway Epithelium Tissue Culture after Exposure to Cigarette Smoke in Vitro

2015 ◽  
Vol 9 ◽  
pp. BBI.S19908 ◽  
Author(s):  
Carole Mathis ◽  
Stephan Gebel ◽  
Carine Poussin ◽  
Vincenzo Belcastro ◽  
Alain Sewer ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Stress Responses ◽  
Epithelial Tissue ◽  
Systems Toxicology ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Transcriptomics Data ◽  
Vitro Model

To establish a relevant in vitro model for systems toxicology-based mechanistic assessment of environmental stressors such as cigarette smoke (CS), we exposed human organotypic bronchial epithelial tissue cultures at the air liquid interface (ALI) to various CS doses. Previously, we compared in vitro gene expression changes with published human airway epithelia in vivo data to assess their similarities. Here, we present a follow-up evaluation of these in vitro transcriptomics data, using complementary computational approaches and an integrated mRNA-microRNA (miRNA) analysis. The main cellular pathways perturbed by CS exposure were related to stress responses (oxidative stress and xenobiotic metabolism), inflammation (inhibition of nuclear factor-kB and the interferon gamma-dependent pathway), and proliferation/differentiation. Within post-exposure periods up to 48 hours, a transient kinetic response was observed at lower CS doses, whereas higher doses resulted in more sustained responses. In conclusion, this systems toxicology approach has potential for product testing according to “21st Century Toxicology”.

Systems Toxicology: Systematic Approach to Predict Toxicity

2017 ◽  
Vol 22 (46) ◽  
pp. 6911-6917 ◽  
Author(s):  
Narsis Kiani ◽  
Ming-Mei Shang ◽  
Jesper Tegner
Keyword(s):  
Systematic Approach ◽  
Systems Toxicology

Pharmacokinetic Drug-drug Interaction of Antibiotics Used in Sepsis Care in China

2020 ◽  
Vol 21 ◽  
Author(s):  
Xuan Yu ◽  
Zixuan Chu ◽  
Jian Li ◽  
Rongrong He ◽  
Yaya Wang ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Penicillin G ◽  
Literature Mining ◽  
Human Pharmacokinetics ◽  
P450 Enzyme ◽  
Drug Drug Interaction ◽  
Pharmacokinetic Drug ◽  
Sepsis Care

Background: Many antibiotics have a high potential for having an interaction with drugs, as perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients. Methods: The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature mining was conducted to obtain human pharmacokinetics/dispositions of the antibiotics, their interactions with drug metabolizing enzymes or transporters, and their associated clinical drug interactions. Potential DDI is indicated by a DDI index > 0.1 for inhibition or a treated-cell/untreated-cell ratio of enzyme activity being > 2 for induction. Results: The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential drug interactions is summarized. Conclusion: Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole) and three lipophilic antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials (ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug transporters in vitro. Despite no reported clinical PK drug interactions with the transporters, caution is advised in the use of these antibacterials. Eight hydrophilic antibacterials (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin, ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims in drug interactions are scarce.

Preliminary Study on the Mechanism of Carvacrol Regulating Hepatocellular Carcinoma Based on Network Pharmacology

2019 ◽  
Vol 16 (11) ◽  
pp. 1286-1295
Author(s):  
Sha Li ◽  
Haixia Zhao ◽  
Lidao Bao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Target Prediction ◽  
Network Pharmacology ◽  
Literature Mining ◽  
Active Compounds ◽  
Prediction Server ◽  
Preliminary Study ◽  
Alignment Analysis ◽  
Endogenous Interactions

Objective: To predict and analyze the target of anti-Hepatocellular Carcinoma (HCC) in the active constituents of Safflower by using network pharmacology. Methods: The active compounds of safflower were collected by TCMSP, TCM-PTD database and literature mining methods. The targets of active compounds were predicted by Swiss Target Prediction server, and the target of anti-HCC drugs was collected by DisGeNET database. The target was subjected to an alignment analysis to screen out Carvacrol, a target of safflower against HCC. The mouse HCC model was established and treated with Carvacrol. The anti-HCC target DAPK1 and PPP2R2A were verified by Western blot and co-immunoprecipitation. Results: A total of 21 safflower active ingredients were predicted. Carvacrol was identified as a possible active ingredient according to the five principles of drug-like medicine. According to Carvacrol's possible targets and possible targets of HCC, three co-targets were identified, including cancer- related are DAPK1 and PPP2R2A. After 20 weeks of Carvacrol treated, Carvacrol group significantly increased on DAPK1 levels and decreased PPP2R2A levels in the model mice by Western blot. Immunoprecipitation confirmed the endogenous interaction between DAPK1 and PPP2R2A. Conclusion: Safflower can regulate the development of HCC through its active component Carvacrol, which can affect the expression of DAPK1 and PPP2R2A proteins, and the endogenous interactions of DAPK1 and PPP2R2A proteins.

scholarly journals Comparison between instrumental variable and mediation-based approaches for reconstructing causal gene networks in yeast

2021 ◽  
Author(s):  
Adriaan-Alexander Ludl ◽  
Tom Michoel
Keyword(s):  
Instrumental Variable ◽  
Gene Networks ◽  
Omics Data ◽  
Causal Gene ◽  
Causal Networks ◽  
Transcriptomics Data ◽  
A Cell ◽  
Flow Of Information

Causal gene networks model the flow of information within a cell. Reconstructing causal networks from omics data is challenging because correlation does not imply causation. When genomics and transcriptomics data...

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