network toxicology

Cynoglossum amabile, a member of the Boraginaceae family, is a well-known traditional Chinese medicine and ethnomedicine known as Daotihu. Despite several studies confirming the presence of bioactive pyrrolizidine alkaloids such as amabiline, ambelline, echinatine, europine, and others in C. amabile , there has been no comprehensive review of its traditional uses, phytochemistry, and pharmacology thus far. This review was conducted by thoroughly examining the literature and analyzing network databases. It covers various aspects of C...

Interaction with chemicals, present in drugs, food, environments, and consumer goods, is an integral part of our everyday life. However, depending on the amount and duration, such interactions can also result in adverse effects. With the increase in computational methods, the in silico methods can offer significant benefits to both regulatory needs and requirements for risk assessments and the pharmaceutical industry to assess the safety profile of a chemical. Here, we present ProTox 3.0, which incorporates molecular similarity and machine-learning models for the prediction of 61 toxicity endpoints such as acute toxicity, organ toxicity, clinical toxicity, molecular-initiating events (MOE), adverse outcomes (Tox21) pathways, several other toxicological endpoints and toxicity off-targets...

The ICH S1B carcinogenicity global testing guideline has been recently revised with a novel addendum that describes a comprehensive integrated Weight of Evidence (WoE) approach to determine the need for a 2-year rat carcinogenicity study. In the present work, experts from different organizations have joined efforts to standardize as much as possible a procedural framework for the integration of evidence associated with the different ICH S1B(R1) WoE criteria. The framework uses a pragmatic consensus procedure for carcinogenicity hazard assessment to facilitate transparent, consistent, and documented decision-making and it discusses best-practices both for the organization of studies and presentation of data in a format suitable for regulatory review...

Long-term and high-dose prescription opioid use places individuals at risk for opioid misuse, opioid use disorder (OUD), and overdose. Existing methods for monitoring opioid use and detecting misuse rely on self-reports, which are prone to reporting bias, and toxicology testing, which may be infeasible in outpatient settings. Although wearable technologies for monitoring day-to-day health metrics have gained significant traction in recent years due to their ease of use, flexibility, and advancements in sensor technology, their application within the opioid use space remains underexplored...

Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 μg/L) for 21 days significantly enhanced the toxicity of DBP (100 μg/L) and BBP (100 μg/L) to Daphnia magna by 18...

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first-line drugs for regulating blood lipids and treating hyperlipidemia-related cardiovascular diseases. However, ATV-associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV-induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 μM) and demonstrated the effects of BBR (10, 50, and 100 μM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish...

BACKGROUND: Dialysis patients are at high risk for drug-related problems (DRPs), which have significant consequences for their morbidity, mortality, and quality of life. Improved clinical outcomes can be achieved by preventing, identifying, and resolving these problems. METHODS: This is a retrospective observational study. In this study, the PAIR instrument (Pharmacotherapy Assessment in Chronic Renal Disease) was validated for use in Turkish. Validation consisted of three stages: translation back-translation with expert panel evaluation, reliability analysis using the test-retest method, and conceptual validity with both Pharmaceutical Care Network Europe (PCNE) and PAIR used to determine DRPs prevalence...

Arsenic (As) is a heavy metal known for its detrimental effects on the kidneys, but the precise mechanisms underlying its toxicity remain unclear. In this study, we employed an integrated approach combining traditional toxicology methods with functional metabolomics to explore the nephrotoxicity induced by As in mice. Our findings demonstrated that after 28 days of exposure to sodium arsenite, blood urea nitrogen, serum creatinine levels were significantly increased, and pathological examination of the kidneys revealed dilation of renal tubules and glomerular injury...

OBJECTIVE: The aim of this study was to investigate the potential risk of drug-induced liver injury (DILI) caused by the CDK4/6 inhibitors (CDK4/6is abemaciclib, ribociclib, and palbociclib by comprehensively analyzing the FDA Adverse Event Reporting System (FAERS) database. Moreover, potential toxicological mechanisms of CDK4/6is-related liver injury were explored via drug-gene network analysis. METHODS: In this retrospective observational study, we collected reports of DILI associated with CDK4/6i use from the FAERS dated January 2014 to March 2023...

"White pollution" has a significant impact on male reproduction. Di-n-butyl phthalate (DBP) is one of the most important factors in this type of pollution. Currently, research from international sources has demonstrated the significant reproductive toxicity of DBP. However, most of these studies have focused mainly on hormones expression at the protein and mRNA levels and the specific molecular targets of DBP and its mechanisms of action remain unclear. In this study, we established a Sprague Dawley pregnant mouse model exposed to DBP, and all male offspring were immediately euthanized at birth and bilateral testes were collected...

Due to continuous plantation of poplar, its growth and biomass accumulation may be negatively affected by the accumulation of allelochemicals such as para-hydroxybenzoic acid (pHBA) in soil. As photosynthesis is the most fundamental process in plants, it can be negatively impacted by pHBA stress. Therefore, it is crucial to improve photosynthetic capacity under pHBA stress to facilitate poplar plant growth. The mitogen-activated protein kinase (MAPK) cascade pathway is widely involved in environmental stress responses in plants...

Deoxynivalenol is a widespread feed contaminant that leads to vomit, which results in serious symptom such as increased intestinal permeability and even intestinal mucosal necrosis. Recent studies have reported the role of quercetin in alleviating deoxynivalenol-induced intestinal injury; however, the mechanisms and targets remain unclear. Thus, we aimed to identify the mechanisms of action by using a combination of network pharmacology and molecular docking. We identified 151 quercetin targets, 235 deoxynivalenol targets and 47 porcine intestinal injury targets by searching compound database and PubMed database, among which there were two common targets...

PURPOSE OF THIS REVIEW: Manipulating or re-engineering the damaged human spinal cord to achieve neuro-recovery is one of the foremost challenges of modern science. Addressing the restricted permission of neural cells and topographically organised neural tissue for self-renewal and spontaneous regeneration, respectively, is not straightforward, as exemplified by rare instances of translational success. This review assembles an understanding of advances in nanomedicine for spinal cord injury (SCI) and related clinical indications of relevance to attempts to design, engineer, and target nanotechnologies to multiple molecular networks...

BACKGROUND: The metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI. METHODS: Genes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI...

Introduction: Adverse Outcome Pathways (AOPs) can support both testing and assessment of endocrine disruptors (EDs). There is, however, a need for further development of the AOP framework to improve its applicability in a regulatory context. Here we have inventoried the AOP-wiki to identify all existing AOPs related to mammalian reproductive toxicity arising from disruption to the estrogen, androgen, and steroidogenesis modalities. Core key events (KEs) shared between relevant AOPs were also identified to aid in further AOP network (AOPN) development...

BACKGROUND: Seniors with recurrent hospitalizations who are taking multiple medications including high-risk medications are at particular risk for serious adverse medication events. We will assess whether an expert Clinical Pharmacology and Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care is feasible and can decrease drug therapy problems amongst this group. METHODS: The design is a pragmatic pilot randomized trial with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis...

Exposure to pesticides, such as carbamates, organophosphates, organochlorines and pyrethroids, has been linked to various health problems, including neurotoxicity. Although most in vivo studies use only male rodents, some studies have shown in vivo sex-specific effects after acute exposure. Since in vivo studies are costly and require a large number of animals, in vitro assays that take sex-specific effects into account are urgently needed. We therefore assessed the acute effects of exposure to different carbamates (methomyl, aldicarb and carbaryl), organophosphates (chlorpyrifos (CPF), chlorpyrifos-oxon (CPO) and 3,5,6-trichloropyridinol), organochlorines (endosulfan, dieldrin and lindane) and pyrethroids (permethrin, alpha-cypermethrin and 3-phenoxy-benzoic acid (3-PBA)) on neuronal network function in sex-separated rat primary cortical cultures using micro-electrode array (MEA) recordings...

BackgroundDevelopmental toxicity tests are extremely expensive, require a large number of animals, and are time-consuming. It is necessary to develop a new approach to simplify the analysis of developmental endpoints. One of these endpoints is malformation, and one group of ongoing methods for simplifying is in silico models. In this study, we aim to develop a Quantitive Structure- Activity Relationship (QSAR) model and identify the best algorithm for predicting malformations, as well as the most important and effective physicochemical properties associated with malformation...

As a protein kinase inhibitor, cantharidin (CTD) exhibits antitumor activities. However, CTD is highly toxic, thereby limiting clinical applications. Moreover, relatively few studies have investigated CTD-induced reproductive toxicity, thus the underlying mechanism remains unclear. In this study, the toxic effects of CTD on mouse testis were confirmed in vivo and the potential mechanism was predicted by network toxicology (NT) and molecular docking technology. Proteins involved in the signaling pathways and core targets were verified...

New human life begins in the uterus in a period of both extreme plasticity and sensitivity to environmental disturbances. The fetal stage is also a vital period for central nervous system development, with experiences at this point profoundly and permanently shaping brain structure and function. As such, some brain disorders may originate in utero. Glucocorticoids, a class of essential stress hormones, play indispensable roles in fetal development, but overexposure may have lasting impacts on the brain. In this review, we summarize data from recent clinical and non-clinical studies regarding alterations in fetal brains due to prenatal glucocorticoid overexposure that are associated with nervous system disorders...