1,2:3,4-Diepoxybutane Induces Multipolar Mitosis in Cultured Human Lymphocytes

Torres, René; Cruz, Martín Daniel Domínguez; Gutiérrez, César; Ramírez-Dueñas, María de Lourdes; Torres, Miquel; Garcı́a, Jesús

doi:10.1159/000445858

Cited by 5 publications

(5 citation statements)

References 47 publications

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“… 58 These cells play a critical role in the immune system, which can help us fight against various diseases in the human body. 59 Hodgkin lymphoma and non-Hodgkin lymphoma are two main kinds of lymphoma that can happen in both children and adults. 60 Recently, many miRNAs have been verified to be associated with lymphoma in different mechanisms.…”

Section: Resultsmentioning

confidence: 99%

Novel Human miRNA-Disease Association Inference Based on Random Forest

Chen

Wang

Yin

et al. 2018

Molecular Therapy - Nucleic Acids

106

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Since the first microRNA (miRNA) was discovered, a lot of studies have confirmed the associations between miRNAs and human complex diseases. Besides, obtaining and taking advantage of association information between miRNAs and diseases play an increasingly important role in improving the treatment level for complex diseases. However, due to the high cost of traditional experimental methods, many researchers have proposed different computational methods to predict potential associations between miRNAs and diseases. In this work, we developed a computational model of Random Forest for miRNA-disease association (RFMDA) prediction based on machine learning. The training sample set for RFMDA was constructed according to the human microRNA disease database (HMDD) version (v.)2.0, and the feature vectors to represent miRNA-disease samples were defined by integrating miRNA functional similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity. The Random Forest algorithm was first employed to infer miRNA-disease associations. In addition, a filter-based method was implemented to select robust features from the miRNA-disease feature set, which could efficiently distinguish related miRNA-disease pairs from unrelated miRNA-disease pairs. RFMDA achieved areas under the curve (AUCs) of 0.8891, 0.8323, and 0.8818 ± 0.0014 under global leave-one-out cross-validation, local leave-one-out cross-validation, and 5-fold cross-validation, respectively, which were higher than many previous computational models. To further evaluate the accuracy of RFMDA, we carried out three types of case studies for four human complex diseases. As a result, 43 (esophageal neoplasms), 46 (lymphoma), 47 (lung neoplasms), and 48 (breast neoplasms) of the top 50 predicted disease-related miRNAs were verified by experiments in different kinds of case studies. The results of cross-validation and case studies indicated that RFMDA is a reliable model for predicting miRNA-disease associations.

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Section: Resultsmentioning

confidence: 99%

Novel Human miRNA-Disease Association Inference Based on Random Forest

Chen

Wang

Yin

et al. 2018

Molecular Therapy - Nucleic Acids

106

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“…3 E-H) or exhibited a multipolar mitosis-like chromosome organization (Fig. 3 I-L) (for comparison, see Barajas-Torres et al, 2016 [ 10 ]).…”

Section: Case Presentationmentioning

confidence: 88%

Chromosomal instability in a patient with ring chromosome 14 syndrome: a case report

Meza-Espinoza,

González-García,

Nieto-Marín

et al. 2024

Mol Cytogenet

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Background Ring chromosome 14 syndrome is a rare disorder primarily marked by early-onset epilepsy, microcephaly, distinctive craniofacial features, hypotonia, intellectual disability, and delay in both development and language acquisition. Case presentation A 21-year-old woman with a history of epileptic seizures since the age of 1.5 years presented with distinctive craniofacial features, including a prominent and narrow forehead, sparse and short eyebrows, palpebral ptosis, horizontal palpebral fissures, a broad nasal bridge, a prominent nasal tip, a flat philtrum, hypertelorism, midfacial hypoplasia, horizontal labial fissures, a thin upper lip, crowded teeth, an ogival palate, retrognathia, and a wide neck. Additional physical abnormalities included kyphosis, lumbar scoliosis, pectus carinatum, cubitus valgus, thenar and hypothenar hypoplasia, bilateral hallux valgus, shortening of the Achilles tendon on the left foot, and hypoplasia of the labia minora. Chromosomal analysis identified a ring 14 chromosome with breakpoints in p11 and q32.33. An aCGH study revealed a ~ 1.7 Mb deletion on chromosome 14qter, encompassing 23 genes. Genomic instability was evidenced by the presence of micronuclei and aneuploidies involving the ring and other chromosomes. Conclusion The clinical features of our patient closely resembled those observed in other individuals with ring chromosome 14 syndrome. The most important point was that we were able to verify an instability of the r(14) chromosome, mainly involving anaphasic lags and its exclusion from the nucleus in the form of a micronucleus.

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“…[ 1,3 ] BD is a known mutagen, carcinogen, genotoxin, and teratogen, and its toxic effects are mediated primarily through its three epoxide metabolites, with DEB being the most potent. [ 1,4–7 ] DEB induces oxidative stress, DNA lesions, protein crosslinks, intra‐strand and interstrand DNA–DNA crosslinks, and apoptosis. [ 8–15 ] The molecular mechanisms of BD and DEB‐induced toxicity are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Diepoxybutane induces the p53‐dependent transactivation of the CCL4 gene that mediates apoptosis in exposed human lymphoblasts

Ewunkem

Deve

Harrison

et al. 2023

J Biochem & Molecular Tox

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Diepoxybutane (DEB) is the most toxic metabolite of the environmental chemical 1,3-butadiene. We previously demonstrated the occurrence of DEB-induced p53mediated apoptosis in human lymphoblasts. The p53 protein functions as a master transcriptional regulator in orchestrating the genomic response to a variety of stress signals. Transcriptomic analysis indicated that C-C chemokine ligand 4 (CCL4) gene expression was elevated in a p53-dependent manner in DEB-exposed p53-proficient TK6 cells, but not in DEB-exposed p53-deficient NH32 cells. Thus, the objective of this study was to determine whether the CCL4 gene is a transcriptional target of p53 and deduce its role in DEB-induced apoptosis in human lymphoblasts. Endogenous and exogenous wild-type p53 transactivated the activity of the CCL4 promoter in DEB-exposed lymphoblasts, but mutant p53 activity on this promoter was reduced by ∼80% under the same experimental conditions. Knockdown of the upregulated CCL4 mRNA levels in p53-proficient TK6 cells inhibited DEB-induced apoptosis by ∼45%-50%. Collectively, these observations demonstrate for the first time that the CCL4 gene is upregulated by wild-type p53 at the transcriptional level, and this upregulation mediates apoptosis in DEB-exposed human lymphoblasts.

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1,2:3,4-Diepoxybutane Induces Multipolar Mitosis in Cultured Human Lymphocytes

Cited by 5 publications

References 47 publications

Novel Human miRNA-Disease Association Inference Based on Random Forest

Novel Human miRNA-Disease Association Inference Based on Random Forest

Chromosomal instability in a patient with ring chromosome 14 syndrome: a case report

Diepoxybutane induces the p53‐dependent transactivation of the CCL4 gene that mediates apoptosis in exposed human lymphoblasts

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