Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy.

Abstract:

:A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity.

journal_name

Int J Mol Sci

authors

Chavan S,Friedman R,Nicholls IA

doi

10.3390/ijms160511659

subject

Has Abstract

pub_date

2015-05-21 00:00:00

pages

11659-77

issue

5

issn

1422-0067

pii

ijms160511659

journal_volume

16

pub_type

杂志文章
  • CSPG4 as Target for CAR-T-Cell Therapy of Various Tumor Entities-Merits and Challenges.

    abstract::Targeting cancer cells using chimeric-antigen-receptor (CAR-)T cells has propelled adoptive T-cell therapy (ATT) to the next level. A plentitude of durable complete responses using CD19-specific CAR-T cells in patients suffering from various lymphoid malignancies resulted in the approval by the food and drug administr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20235942

    authors: Harrer DC,Dörrie J,Schaft N

    更新日期:2019-11-26 00:00:00

  • Identification, Characterization and Synthesis of Walterospermin, a Sperm Motility Activator from the Egyptian Black Snake Walterinnesia aegyptia Venom.

    abstract::Animal venoms are small natural mixtures highly enriched in bioactive components. They are known to target at least two important pharmacological classes of cell surface receptors: ion channels and G protein coupled receptors. Since sperm cells express a wide variety of ion channels and membrane receptors, required fo...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21207786

    authors: Abd El-Aziz TM,Jaquillard L,Bourgoin-Voillard S,Martinez G,Triquigneaux M,Zoukimian C,Combemale S,Hograindleur JP,Al Khoury S,Escoffier J,Michelland S,Bulet P,Beroud R,Seve M,Arnoult C,De Waard M

    更新日期:2020-10-21 00:00:00

  • Injectable Gel Form of a Decellularized Bladder Induces Adipose-Derived Stem Cell Differentiation into Smooth Muscle Cells In Vitro.

    abstract::Biologic scaffolds composed of extracellular matrix components have been proposed to repair and reconstruct a variety of tissues in clinical and pre-clinical studies. Injectable gels can fill and conform any three-dimensional shape and can be delivered to sites of interest by minimally invasive techniques. In this stu...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21228608

    authors: Moreno-Manzano V,Zaytseva-Zotova D,López-Mocholí E,Briz-Redón Á,Løkensgard Strand B,Serrano-Aroca Á

    更新日期:2020-11-15 00:00:00

  • The role of microRNAs in breast cancer migration, invasion and metastasis.

    abstract::MicroRNAs (miRNAs) are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. Many miRNAs have been impli...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms131013414

    authors: Tang J,Ahmad A,Sarkar FH

    更新日期:2012-10-18 00:00:00

  • Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure-Activity Relationship Study.

    abstract::The evaluation of antioxidant compounds that counteract the mutagenic effects caused by the direct action of reactive oxygen species on DNA molecule is of considerable interest. Therefore, a series of 2,3-substituted quinazolinone derivatives (Q1-Q8) were investigated by different assays, and the relationship between ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms22020610

    authors: Hricovíniová J,Hricovíniová Z,Kozics K

    更新日期:2021-01-09 00:00:00

  • Exosomal Expression of CXCR4 Targets Cardioprotective Vesicles to Myocardial Infarction and Improves Outcome after Systemic Administration.

    abstract::Cell therapy has been evaluated to enhance heart function after injury. Delivered cells mostly act via paracrine mechanisms, including secreted growth factors, cytokines, and vesicles, such as exosomes (Exo). Intramyocardial injection of cardiac-resident progenitor cells (CPC)-derived Exo reduced scarring and improved...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20030468

    authors: Ciullo A,Biemmi V,Milano G,Bolis S,Cervio E,Fertig ET,Gherghiceanu M,Moccetti T,Camici GG,Vassalli G,Barile L

    更新日期:2019-01-22 00:00:00

  • The Role of BRAF in Metastatic Colorectal Carcinoma-Past, Present, and Future.

    abstract::With a global incidence of 1.8 million cases, colorectal cancer represents one of the most common cancers worldwide. Despite impressive improvements in treatment efficacy through cytotoxic and biological agents, the cancer-related death burden of metastatic colorectal cancer (mCRC) is still high. mCRC is not a genetic...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21239001

    authors: Djanani A,Eller S,Öfner D,Troppmair J,Maglione M

    更新日期:2020-11-26 00:00:00

  • Mapping Quantitative Trait Loci (QTL) for Resistance to Late Blight in Tomato.

    abstract::Late blight caused by Phytophthora infestans (Montagne, Bary) is a devastating disease of tomato worldwide. There are three known major genes, Ph-1, Ph-2, and Ph-3, conferring resistance to late blight. In addition to these three genes, it is also believed that there are additional factors or quantitative trait loci (...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms18071589

    authors: Panthee DR,Piotrowski A,Ibrahem R

    更新日期:2017-07-22 00:00:00

  • Revisiting the Role of LXRs in PUFA Metabolism and Phospholipid Homeostasis.

    abstract::Liver X receptors (LXRs) play a pivotal role in fatty acid (FA) metabolism. So far, the lipogenic consequences of in vivo LXR activation, as characterized by a major hepatic steatosis, has constituted a limitation to the clinical development of pharmacological LXR agonists. However, recent studies provided a different...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20153787

    authors: Jalil A,Bourgeois T,Ménégaut L,Lagrost L,Thomas C,Masson D

    更新日期:2019-08-02 00:00:00

  • Expression and Functional Properties of an Anti-Triazophos High-Affinity Single-Chain Variable Fragment Antibody with Specific Lambda Light Chain.

    abstract::Triazophos is a widely used organophosphorous insecticide that has potentially adverse effects to organisms. In the present study, a high-affinity single-chain variable fragment (scFv) antibody with specific lambda light chain was developed for residue monitoring. First, the specific variable regions were correctly am...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms17060823

    authors: Liu R,Liang X,Xiang D,Guo Y,Liu Y,Zhu G

    更新日期:2016-06-07 00:00:00

  • The Role of Cell Adhesion Molecule 1 (CADM1) in Cutaneous Malignancies.

    abstract::Cell adhesion ability is one of the components to establish cell organization and shows a great contribution to human body construction consisting of various types of cells mixture to orchestrate tissue specific function. The cell adhesion molecule 1 (CADM1) is a molecule of cell adhesion with multiple functions and h...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21249732

    authors: Sawada Y,Mashima E,Saito-Sasaki N,Nakamura M

    更新日期:2020-12-20 00:00:00

  • Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection.

    abstract::Although the application of cardioprotective ischaemia/reperfusion (I/R) stimuli after myocardial infarction (MI) is a promising concept for salvaging the myocardium, translation to a clinical scenario has not fulfilled expectations. We have previously shown that in pigs, ischaemic postconditioning (IPostC) reduces my...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20020344

    authors: Lukovic D,Gugerell A,Zlabinger K,Winkler J,Pavo N,Baranyai T,Giricz Z,Varga ZV,Riesenhuber M,Spannbauer A,Traxler D,Jakab A,Garamvölgyi R,Petnehazy Ö,Pils D,Tóth L,Schulz R,Ferdinandy P,Gyöngyösi M

    更新日期:2019-01-15 00:00:00

  • Implications of a Soy-Based Diet for Animal Models.

    abstract::The use of animal models in fundamental or pre-clinical research remains an absolute requirement for understanding human pathologies and developing new drugs. In order to transpose these results into clinical practice, many parameters must be taken into account to limit bias. Attention has recently been focused on the...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms22020774

    authors: Dhot J,Prat V,Ferron M,Aillerie V,Erraud A,Rozec B,Waard M,Gauthier C,Lauzier B

    更新日期:2021-01-14 00:00:00

  • Phytochemicals Targeting Estrogen Receptors: Beneficial Rather Than Adverse Effects?

    abstract::In mammals, the effects of estrogen are mainly mediated by two different estrogen receptors, ERα and ERβ. These proteins are members of the nuclear receptor family, characterized by distinct structural and functional domains, and participate in the regulation of different biological processes, including cell growth, s...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms18071381

    authors: Lecomte S,Demay F,Ferrière F,Pakdel F

    更新日期:2017-06-28 00:00:00

  • Involvement of Aquaporins in the Pathogenesis, Diagnosis and Treatment of Sjögren's Syndrome.

    abstract::Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands resulting in diminished production of saliva and tears. The pathophysiology of SS has not yet been fully deciphered. Classically it has been postulated that sicca symptoms in SS patients ar...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms19113392

    authors: Soyfoo MS,Chivasso C,Perret J,Delporte C

    更新日期:2018-10-30 00:00:00

  • Biological Properties, Bioactive Constituents, and Pharmacokinetics of Some Capsicum spp. and Capsaicinoids.

    abstract::Pepper originated from the Capsicum genus, which is recognized as one of the most predominant and globally distributed genera of the Solanaceae family. It is a diverse genus, consisting of more than 31 different species including five domesticated species, Capsicum baccatum, C. annuum, C. pubescen, C. frutescens, and ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21155179

    authors: Batiha GE,Alqahtani A,Ojo OA,Shaheen HM,Wasef L,Elzeiny M,Ismail M,Shalaby M,Murata T,Zaragoza-Bastida A,Rivero-Perez N,Magdy Beshbishy A,Kasozi KI,Jeandet P,Hetta HF

    更新日期:2020-07-22 00:00:00

  • Polyvinyl Butyral (PVB) Nanofiber/Nanoparticle-Covered Yarns for Antibacterial Textile Surfaces.

    abstract::In this study, nanoparticle-incorporated nanofiber-covered yarns were prepared using a custom-made needle-free electrospinning system. The ultimate goal of this work was to prepare functional nanofibrous surfaces with antibacterial properties and realize high-speed production. As antibacterial agents, we used various ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20174317

    authors: Yalcinkaya F,Komarek M

    更新日期:2019-09-03 00:00:00

  • Structural Aspects and Prediction of Calmodulin-Binding Proteins.

    abstract::Calmodulin (CaM) is an important intracellular protein that binds Ca2+ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM's ability to adapt to binding targets with different structures is related to the flexible centra...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms22010308

    authors: Andrews C,Xu Y,Kirberger M,Yang JJ

    更新日期:2020-12-30 00:00:00

  • Characterization and Immobilization of a Novel SGNH Family Esterase (LaSGNH1) from Lactobacillus acidophilus NCFM.

    abstract::The SGNH family esterases are highly effective biocatalysts due to their strong catalytic efficiencies, great stabilities, relatively small sizes, and ease of immobilization. Here, a novel SGNH family esterase (LaSGNH1) from Lactobacillus acidophilus NCFM, which has homologues in many Lactobacillus species, was identi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21010091

    authors: Le LTHL,Yoo W,Jeon S,Kim KK,Kim TD

    更新日期:2019-12-21 00:00:00

  • Functional Role of the C-Terminal Amphipathic Helix 8 of Olfactory Receptors and Other G Protein-Coupled Receptors.

    abstract::G protein-coupled receptors (GPCRs) transduce various extracellular signals, such as neurotransmitters, hormones, light, and odorous chemicals, into intracellular signals via G protein activation during neurological, cardiovascular, sensory and reproductive signaling. Common and unique features of interactions between...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms17111930

    authors: Sato T,Kawasaki T,Mine S,Matsumura H

    更新日期:2016-11-18 00:00:00

  • A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease.

    abstract::Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible indiv...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms18071534

    authors: Dongiovanni P,Valenti L

    更新日期:2017-07-16 00:00:00

  • Deregulation of Frizzled Receptors in Hepatocellular Carcinoma.

    abstract::G protein-coupled receptors (GPCRs) have a substantial role in tumorigenesis and are described as a "cancer driver". Aberrant expression or activation of GPCRs leads to the deregulation of downstream signaling pathways, thereby promoting cancer progression. In hepatocellular carcinoma (HCC), the Wnt signaling pathway ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms19010313

    authors: Chan KK,Lo RC

    更新日期:2018-01-21 00:00:00

  • Impact of PPAR-Alpha Polymorphisms-The Case of Metabolic Disorders and Atherosclerosis.

    abstract::Peroxisome proliferator activated receptor α (PPARα) has the most relevant biological functions among PPARs. Activation by drugs and dietary components lead to major metabolic changes, from reduced triglyceridemia to improvement in the metabolic syndrome. Polymorphisms of PPARα are of interest in order to improve our ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20184378

    authors: Ruscica M,Busnelli M,Runfola E,Corsini A,Sirtori CR

    更新日期:2019-09-06 00:00:00

  • Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism, Oxidative and Immune Status in Preweaning Calves.

    abstract::The objective of this study was to determine the effects of feeding protein-iron complex (PIC) on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf's life. Preparation of the complex involved enzymatic hydrolysis of milk casein...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms18071501

    authors: Kupczyński R,Bednarski M,Śpitalniak K,Pogoda-Sewerniak K

    更新日期:2017-07-12 00:00:00

  • Ectopic Expression of a R2R3-MYB Transcription Factor Gene LjaMYB12 from Lonicera japonica Increases Flavonoid Accumulation in Arabidopsis thaliana.

    abstract::Lonicera japonica Thunb. is a widely used medicinal plant and is rich in a variety of active ingredients. Flavonoids are one of the important components in L. japonica and their content is an important indicator for evaluating the quality of this herb. To study the regulation of flavonoid biosynthesis in L. japonica, ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20184494

    authors: Qi X,Fang H,Chen Z,Liu Z,Yu X,Liang C

    更新日期:2019-09-11 00:00:00

  • Involvement of Satellite Cell Activation via Nitric Oxide Signaling in Ectopic Orofacial Hypersensitivity.

    abstract::: The mechanical head-withdrawal threshold (MHWT) was significantly reduced following inferior alveolar nerve transection (IANX) in rats. Nitrate and nitrite synthesis was dramatically increased in the trigeminal ganglion (TG) at 6 h after the IANX. The relative number of neuronal nitric oxide synthase (nNOS)-immunore...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21041252

    authors: Lee J,Ohara K,Shinoda M,Hayashi Y,Kubo A,Sugawara S,Asano S,Soma K,Kanno K,Ando M,Koyama R,Kimura Y,Sakanashi K,Iinuma T,Iwata K

    更新日期:2020-02-13 00:00:00

  • cGMP Signaling in the Cardiovascular System-The Role of Compartmentation and Its Live Cell Imaging.

    abstract::The ubiquitous second messenger 3',5'-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms19030801

    authors: Bork NI,Nikolaev VO

    更新日期:2018-03-10 00:00:00

  • Theranostics Aspects of Various Nanoparticles in Veterinary Medicine.

    abstract::Nanoscience and nanotechnology shows immense interest in various areas of research and applications, including biotechnology, biomedical sciences, nanomedicine, and veterinary medicine. Studies and application of nanotechnology was explored very extensively in the human medical field and also studies undertaken in rod...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms19113299

    authors: Bai DP,Lin XY,Huang YF,Zhang XF

    更新日期:2018-10-24 00:00:00

  • Chemopreventive Agent 3,3'-Diindolylmethane Inhibits MDM2 in Colorectal Cancer Cells.

    abstract::3,3'-Diindolylmethane (DIM) is a naturally derived chemopreventive compound. It comes from glucobrassicin, an indole glucosinolate enriched in cruciferous vegetables, and is formed in the acidic environment of the stomach after ingestion. Mouse double minute 2 homolog (MDM2) is an important, multi-functional oncogenic...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21134642

    authors: Gao X,Liu J,Cho KB,Kedika S,Guo B

    更新日期:2020-06-30 00:00:00

  • Thermal Stability and Rheological Properties of Epoxidized Natural Rubber-Based Magnetorheological Elastomer.

    abstract::Determination of the thermal characteristics and temperature-dependent rheological properties of the magnetorheological elastomers (MREs) is of paramount importance particularly with regards to MRE applications. Hitherto, a paucity of temperature dependent analysis has been conducted by MRE researchers. In this study,...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20030746

    authors: Yunus NA,Mazlan SA,Ubaidillah.,Abdul Aziz SA,Tan Shilan S,Abdul Wahab NA

    更新日期:2019-02-10 00:00:00