Articles de revues : « Molecules - Toxicological Interest »

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Manini, P., R. Andreoli, A. Mutti, E. Bergamaschi, I. Franchini et W. M. A. Niessen. « Determination of glucuronides of molecules of toxicological interest by liquid chromatography negative-ion mass spectrometry with atmospheric pressure chemical ionization ». Chromatographia 47, n^o 11-12 (juin 1998) : 659–66. http://dx.doi.org/10.1007/bf02467450.

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Amine, Boumelik Mohamed, Ahmed Youcef, Radja Feriel, Moulai Isra Amel, Belhadj Lahcène et Boublenza Abdellatif. « The value of toxicology in determining cause of death. A study of 400 autopsy cases ». STUDIES IN HEALTH SCIENCES 4, n^o 1 (28 avril 2023) : 266–83. http://dx.doi.org/10.54022/shsv4n1-028.

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The interest of a forensic autopsy is the search for the cause of death. However, sometimes doubt suspicion persists about association with toxic substances. In this perspective, it’s important to ask whether such toxicological analyses following a forensic autopsy are important in determining the cause of death. On the other hand, ask yourself, which toxins are most frequently encountered. The question then being is to compare the results of toxicological analyses with the conclusions established during the forensic autopsy. We have tried to show that, during the search for the cause of death, toxicological analyses are essential to assess the participation of xenobiotics in the fatal process. Materials and methods: This is a retrospective study, descriptive study on the analysis of toxicological results compared with conclusions from forensic autopsies (N=400), performed on requisition from the judicial authority of the competent territory, in the forensic medicine department (thanatology unit) of the university hospital of Sidi Bel Abbés (Algeria) during the period from January 01,2017 to December 31,2019. The sampling is carried out on different body fluids to determine how the person died. We had at our disposal blood (cardiac and peripheral), urine, gastric contents. Results: we obtained on our sample of 400, 274 males for 126 females with a sex ratio of 2.17. The minimum age was 0 days. The maximum age was 93 years, with a mean of 38 years and a standard deviation of 23 years. The natural form of death represented 41%, the unatural form (suicidal, criminal, accidental) represented 37% and the undetermined form represented 23%. According to the direct causes of death, acute cardiorespiratory distress represents the majority, i.e. 78.5%. Cardiopulmonary diseases represent the majority (28%), followed by death of traumatic origin (23.3%), death of asphyxic origin (12%) and having remained undetermined (19%). Requests for toxicological analysis of autopsies, including the establishment of the cause of death requiring the results of toxicological analysis represent (45%). Of all the results received (N=42), we found that the results that came back positive represent 43%, of which the molecules with neuro-psychotropic effects represent the majority of 50%, then alcohol (20%) and cannabis (10%). Conclusion: In current forensic practice, the performance and analysis of samples for toxicological purposes appears to be an essential step, in order to better understand the circumstances of unatural deaths, and to clarify some situations for which the cause of death does not appear obvious. The evaluation of the nature of the substances most frequently encountered in search for causes of death can be evaluated over time according to the modes of prescription.

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Gangwar, Mayank, R. K. Goel et Gopal Nath. « Mallotus philippinensisMuell. Arg (Euphorbiaceae) : Ethnopharmacology and Phytochemistry Review ». BioMed Research International 2014 (2014) : 1–13. http://dx.doi.org/10.1155/2014/213973.

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Mallotus philippinensisMuell. Arg (Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions with an altitude below 1,000 m and are reported to have wide range of pharmacological activities.Mallotus philippinensisspecies are known to contain different natural compounds, mainly phenols, diterpenoids, steroids, flavonoids, cardenolides, triterpenoids, coumarins, isocoumarins, and many more especially phenols; that is, bergenin, mallotophilippinens, rottlerin, and isorottlerin have been isolated, identified, and reported interesting biological activities such as antimicrobial, antioxidant, antiviral, cytotoxicity, antioxidant, anti-inflammatory, immunoregulatory activity protein inhibition against cancer cell. We have selected all the pharmacological aspects and toxicological and all its biological related studies. The present review reveals thatMallotus philippinensisis a valuable source of medicinally important natural molecules and provides convincing support for its future use in modern medicine. However, the existing knowledge is very limited aboutMallotus philippinensisand its different parts like steam, leaf, and fruit. Further, more detailed safety data pertaining to the acute and subacute toxicity and cardio- and immunotoxicity also needs to be generated for crude extracts or its pure isolated compounds. This review underlines the interest to continue the study of this genus of the Euphorbiaceae.

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Zhang, Yao, Jie Li, Guoyu Ren, Baofu Qin et Haixia Ma. « Synthesis, crystal structure and antifungal activity of a divalent cobalt(II) complex with uniconazole ». Acta Crystallographica Section C Structural Chemistry 72, n^o 6 (18 mai 2016) : 485–90. http://dx.doi.org/10.1107/s2053229616007750.

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Azole compounds have attracted commercial interest due to their high bactericidal and plant-growth-regulating activities. Uniconazole [or 1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pent-1-en-3-ol] is a highly active 1,2,4-triazole fungicide and plant-growth regulator with low toxicity. The pharmacological and toxicological properties of many drugs are modified by the formation of their metal complexes. Therefore, there is much interest in exploiting the coordination chemistry of triazole pesticides and their potential application in agriculture. However, reports of complexes of uniconazole are rare. A new cobalt(II) complex of uniconazole, namely dichloridotetrakis[1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl-κN4)pent-1-en-3-ol]cobalt(II), [CoCl2(C15H18ClN3O)4], was synthesized and structurally characterized by element analysis, IR spectrometry and X-ray single-crystal diffraction. The crystal structural analysis shows that the CoIIatom is located on the inversion centre and is coordinated by four uniconazole and two chloride ligands, forming a distorted octahedral geometry. The hydroxy groups of an uniconazole ligands of adjacent molecules form hydrogen bonds with the axial chloride ligands, resulting in one-dimensional chains parallel to theaaxis. The complex was analysed for its antifungal activity by the mycelial growth rate method. It was revealed that the antifungal effect of the title complex is more pronounced than the effect of fungicide uniconazole forBotryosphaeria ribis,Wheat gibberellicandGrape anthracnose.

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El Khawaja, Rebecca, Savita Kaliya Perumal Veerapandian, Rim Bitar, Nathalie De Geyter, Rino Morent, Nicolas Heymans, Guy De Weireld et al. « Boosting VOCs elimination by coupling different techniques ». Chemical Synthesis 2, n^o 2 (2022) : 13. http://dx.doi.org/10.20517/cs.2022.10.

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Volatile Organic Compounds (VOCs) are known to be hazardous and harmful to human health and the environment. In mixtures or during repeated exposures, significant toxicity of these compounds in trace amounts has been revealed. In vitro air-liquid interface approaches underlined the interest in evaluating the impact of repeated VOC exposure and the importance of carrying out a toxicological validation of the techniques in addition to the standard chemical analyses. The difficulties in sampling and measuring VOCs in stationary source emissions are due to both the complexity of the mixture present and the wide range of concentrations. The coupling of VOC treatment techniques results in efficient systems with lower operating energy consumption. Three main couplings are outlined in this review, highlighting their advantages and relevance. First, adsorption-catalysis coupling is particularly valuable by using adsorption and catalytic oxidation regeneration initiated, for example, by selective dielectric heating. Then, several key aspects of the plasma catalysis process, such as the choice of catalysts suitable for the non-thermal plasma (NTP) environment, the simultaneous removal of different VOCs, and the in situ regeneration of the catalyst by NTP exposure, are discussed. The adsorption-photocatalysis coupling technology is also one of the effective and promising methods for VOC removal. The VOC molecules strongly adsorbed on the surface of the photocatalyst can be directly oxidized by the photogenerated hole on the photocatalyst (e.g., TiO2).

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Marques, Dayan de Araújo, Fernando Berton Zanchi et Geisa Paulino Caprini Evaristo. « Ethnopharmacological review, phytochemistry and bioactivity of the genus Geissospermum (Apocynaceae) ». Research, Society and Development 12, n^o 2 (3 février 2023) : e18912240047. http://dx.doi.org/10.33448/rsd-v12i2.40047.

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This narrative review aims to update the ethnopharmacology, phytochemistry and biological activities of Geissospermum species described in the literature, in order to contribute to the knowledge of bioactive compounds of therapeutic interest and establish directions for future research with this genus. The term “Geissospermum” was used to perform searches in different databases such as NDLTD (Digital Library Network of Theses and Dissertations), Google Scholar, PubChem, Scifinder, Web of Science, SciELO, PubMed and Science Direct. Google's National Institute of Industrial Property and Patents (INPI) was also consulted. The keywords indole alkaloids, quina-quina, Geissospermum, Geissospermum reticulatum and malaria were used in the search. Publications in Portuguese, French, Spanish and English published between 1950 and 2022 were included. Indole alkaloids are the main secondary metabolites found in this genus, and several molecules have already been isolated, which may be related to the described pharmacological activities. Extracts and isolated compounds showed antitumor, antimalarial, antinociceptive, anti-inflammatory, anticholinesterase, anti-HIV, antimicrobial and antioxidant activity. Plants of the genus Geissospermum are used in Brazil mainly by the Amazonian peoples to treat various pathologies. Biological activities reported for extracts and isolated compounds are consistent with etonopharmacological use against malaria, cancer and other diseases. Future work with Geissospermum species is needed to elucidate the mechanism of action of the isolated alkaloids, as well as their toxicological profile.

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Poulsen-Silva, Erick, Felipe Gordillo-Fuenzalida, Cristian Atala, Adrián A. Moreno et María Carolina Otero. « Bioactive Lichen Secondary Metabolites and Their Presence in Species from Chile ». Metabolites 13, n^o 7 (28 juin 2023) : 805. http://dx.doi.org/10.3390/metabo13070805.

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Lichens are symbiotic organisms composed of at least one fungal and one algal species. They are found in different environments around the world, even in the poles and deserts. Some species can withstand extreme abiotic conditions, including radiation and the vacuum of space. Their chemistry is mainly due to the fungal metabolism and the production of several secondary metabolites with biological activity, which have been isolated due to an increasing interest from the pharmaceutical community. However, beyond the experimental data, little is known about their mechanisms of action and the potential pharmaceutical use of these kinds of molecules, especially the ones isolated from lesser-known species and/or lesser-studied countries. The main objective of this review is to analyze the bibliographical data of the biological activity of secondary metabolites from lichens, identifying the possible mechanisms of action and lichen species from Chile. We carried out a bibliographic revision of different scientific articles in order to collect all necessary information on the biological activity of the metabolites of these lichen species. For this, validated databases were used. We found the most recent reports where in vitro and in vivo studies have demonstrated the biological properties of these metabolites. The biological activity, namely anticancer, antioxidant, and anti-inflammatory activity, of 26 secondary metabolites are described, as well as their reported molecular mechanisms. The most notable metabolites found in this review were usnic acid, atranorin, protolichesterinic acid, and lobaric acid. Usnic acid was the most investigated metabolite, in addition to undergoing toxicological and pharmacological studies, where a hepatotoxicity effect was reported due to uncoupling oxidative phosphorylation. Additionally, no major studies have been made to validate the pharmacological application of these metabolites, and few advancements have been made in their artificial growth in bioreactors. Despite the described biological activities, there is little support to consider these metabolites in pharmaceutical formulations or to evaluate them in clinical trials. Nevertheless, it is important to carry out further studies regarding their possible human health effects. These lichen secondary metabolites present a promising research opportunity to find new pharmaceutical molecules due to their bioactive properties.

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Turkez, Hasan, Ozlem Ozdemir Tozlu, Arzu Tatar, Mehmet Enes Arslan, Kenan Cadirci, Lisa Marinelli, Omer Erkan Yapca, Ivana Cacciatore, Antonio Di Stefano et Adil Mardinoglu. « Toxicity of Glycyl-l-Prolyl-l-Glutamate Pseudotripeptides : Cytotoxic, Oxidative, Genotoxic, and Embryotoxic Perspectives ». Journal of Toxicology 2022 (19 novembre 2022) : 1–8. http://dx.doi.org/10.1155/2022/3775194.

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The tripeptide H-Gly-Pro-Glu-OH (GPE) and its analogs began to take much interest from scientists for developing effective novel molecules in the treatment of several disorders including Alzheimer’s disease, Parkinson’s disease, and stroke. The peptidomimetics of GPEs exerted significant biological properties involving anti-inflammatory, antiapoptotic, and anticancer properties. The assessments of their hematological toxicity potentials are critically required for their possible usage in further preclinical and clinical trials against a wide range of pathological conditions. However, there is so limited information on the safety profiling of GPE and its analogs on human blood tissue from cytotoxic, oxidative, and genotoxic perspectives. And, their embryotoxicity potentials were not investigated yet. Therefore, in this study, measurements of mitochondrial viability (using MTT assay) and lactate dehydrogenase (LDH) release as well as total antioxidant capacity (TAC) assays were performed on cultured human whole blood cells after treatment with GPE and its three novel peptidomimetics for 72 h. Sister chromatid exchange (SCE), micronucleus (MN), and 8-oxo-2-deoxyguanosine (8-OH-dG) assays were performed for determining the genotoxic damage potentials. In addition, the nuclear division index (NDI) was figured out for revealing their cytostatic potentials. Embryotoxicity assessments were performed on cultured human pluripotent NT2 embryonal carcinoma cells by MTT and LDH assays. The present results from cytotoxicity, oxidative, genotoxicity, and embryotoxicity testing clearly propounded that GPEs had good biosafety profiles and were trouble-free from the toxicological point of view. Noncytotoxic, antioxidative, nongenotoxic, noncytostatic, and nonembryotoxic features of GPE analogs are worthwhile exploring further and may exert high potentials for improving the development of novel disease-modifying agents.

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Semmrich, Monika, Jean-Baptiste Marchand, Laetitia Fend, Matilda Rehn, Nathalie Silvestre, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Eric Quéméneur et Björn Frendeus. « 594 BT-001, an oncolytic vaccinia virus armed with a Treg-depleting human recombinant anti-CTLA4 antibody and GM-CSF to target the tumor microenvironment ». Journal for ImmunoTherapy of Cancer 8, Suppl 3 (novembre 2020) : A629. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0594.

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BackgroundCheckpoint inhibitor antibodies have improved survival in a variety of cancers, however, a great unmet need remains since only a small fraction of patients responds. Reasons for lack of efficacy are believed to include lack of tumor infiltrating immune cells, a notion supported by improved efficacy observed following combined checkpoint blockade with tumor oncolytic virotherapy which promotes intratumoral T cell infiltration. Oncolytic vaccinia viruses (oVV) also allow genetic encoding of transgenes. This is of special interest for therapeutic proteins exhibiting toxicological limitation or pharmacokinetic issues. Here, BioInvent and Transgene present a potentially safe and more efficacious strategy to combine checkpoint inhibition in the context of oncolytic virotherapy.MethodsUsing the F.I.R.S.T™ discovery platform we have isolated a human recombinant Treg-depleting antibody that has been vectorized alongside GM-CSF into the Invir.IO® oVV. This product named BT-001 consists of a Copenhagen double deleted vaccinia virus encoding the human CTLA4-specific antibody 4-E03 IgG1, which shows improved Treg-depletion compared with ipilimumab in a human PBMC-based NOG/SCID-transfer model. BT-001 also encodes GM-CSF, the cytokine expressed in clinically approved products. A surrogate murine mAb was vectorized into the same oVV (mBT-1) allowing for functional and mechanistic in vivo studies.ResultsOur studies demonstrate that 4-E03 and GM-CSF were expressed as functional molecules after infection by BT-001 of human tumor cell lines in vitro. Moreover, following intratumoral administration in immune competent and immune deficient mice transplanted with mouse or human tumors, transgene expression was sustained at levels associated with receptor saturation for days to weeks. In contrast, and supporting the tumor-selective nature of oVV, blood concentrations of anti-CTLA4 mAb were lower compared to those observed following i.v. administration of therapeutic doses of mAb. The in vivo anti-tumor activity of mBT-1 was assessed in multiple syngeneic mouse tumor models including CT26, EMT6, A20 and C38. Murine surrogate mBT-1 conferred cures in the majority of challenged mice irrespective of tumor origin. The excellent anti-tumoral profile depends on anti-CTLA4 expression and could be boosted by co-administration of anti-PD-1 mAb. Intratumoral treatment with mBT-1 also induces abscopal anti-tumor responses and protects against tumor rechallenge demonstrating a long-lasting systemic anti-tumor activity.ConclusionsA clinical batch of BT-001 has been produced and toxicological evaluation is ongoing. Transgene and BioInvent have applied for a clinical trial targeting injectable superficial tumors. Here, the tumor-localized delivery of anti-CTLA4 may allow a better tolerated and more effective combination therapy with antibodies targeting the PD-1/PDL1 axis.

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Bertelà, Federica, Martina Marsotto, Cecilia Meneghini, Luca Burratti, Valentin-Adrian Maraloiu, Giovanna Iucci, Iole Venditti et al. « Biocompatible Silver Nanoparticles : Study of the Chemical and Molecular Structure, and the Ability to Interact with Cadmium and Arsenic in Water and Biological Properties ». Nanomaterials 11, n^o 10 (28 septembre 2021) : 2540. http://dx.doi.org/10.3390/nano11102540.

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In the field of research for designing and preparing innovative nanostructured systems, these systems are able to reveal the presence of heavy metals in water samples, and can efficiently and selectively interact with them, allowing for future applications in the field of water remediation. We investigated the electronic and molecular structure, as well as the morphology, of silver nanoparticles stabilized by mixed biocompatible ligands (the amino acid L-cysteine and the organic molecule citrate) in the presence of cadmium and arsenic ions. The molecular, electronic, and local structure at the ligands/silver nanoparticles interface was probed by the complementary synchrotron radiation-induced techniques (SR-XPS, NEXAFS and XAS). The optical absorption (in the UV-Vis range) of the nanosystem was investigated in the presence of Cd(II) and As(III) and the observed behavior suggested a selective interaction with cadmium. In addition, the toxicological profile of the innovative nanosystem was assessed in vitro using a human epithelial cell line HEK293T. We analyzed the viability of the cells treated with silver nanoparticles, as well as the activation of antioxidant response.

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Wille, Sarah M. R., Karolien Van Dijck, Antje Van Assche, Vincent Di Fazio, Maria del Mar Ramiréz-Fernandéz, Vanessa Vanvooren et Nele Samyn. « The Interest of a Systematic Toxicological Analysis Combined with Forensic Advice to Improve the Judicial Investigation and Final Judgment in Drug Facilitated Sexual Assault Cases ». Pharmaceuticals 14, n^o 5 (4 mai 2021) : 432. http://dx.doi.org/10.3390/ph14050432.

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The conviction rate in drug facilitated sexual assault (DFSA) cases is known to be very low. In addition, the potential impact of toxicological results on the case is often not well understood by the judicial authorities. The aims of this study were (1) to obtain more knowledge concerning the prevalence of incapacitating substances in DFSA cases, (2) to create a more efficient DFSA analysis strategy taking background information into account, and (3) to evaluate the potential impact of systematic toxicological analysis (STA) on the final judicial outcome. This small-scale epidemiological study (n = 79) demonstrates that ‘commonly-used’ illicit drugs, psychoactive medicines and ethanol are more prevalent in DFSA cases in contrast to the highly mediatized date rape drugs. Additionally, via case examples, the interest of performing STA—to prove incapacitation of the victim—in judicial procedures with mutual-consent discussions has been demonstrated as it led to increased convictions. However, more attention has to be paid to ensure a short sampling delay and to get more accurate information from the medical treatment of the alleged victim. This will improve the interpretation of the toxicological analysis and thus its applicability in a DFSA case. The future is multi-disciplinary and will certainly lead to an efficient and more cost-effective DFSA approach in which STA can impact the final judgment.

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Garg, Rajni, Gene M. Ko et Carr J. Smith. « QSAR molecular parameters calculated for US EPA ToxCast Phase 1 and 2 chemical compounds tested against embryonic zebrafish ». Toxicology Research and Application 1 (1 janvier 2017) : 239784731770737. http://dx.doi.org/10.1177/2397847317707371.

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Freshwater and marine environments are exposed to small concentrations of many different chemicals produced by industrial, agricultural, pharmaceutical, cosmetic, food, and household applications. Due to concerns regarding potential adverse events from these exposures, regulatory agencies around the world have established aquatic toxicology testing protocols that measure untoward responses in a wide variety of freshwater and marine organisms. Following a literature review of databases on the toxicity of chemicals to fish, the embryonic zebrafish ( Danio rerio) database compiled by the Tanguay Laboratory at Oregon State University was determined to be well suited for quantitative structure–activity relationship (QSAR) analysis. This database possesses a number of favorable characteristics including large size (1060 unique US Environmental Protection Agency ToxCast phase 1 and 2 chemical compounds), relatively recent data collected using state-of-the-art methods, 18 simultaneously measured toxicological end points, transparent embryos that develop externally thereby facilitating toxicological evaluation, and the vast majority of the genetic code is expressed and active during early life stages. The molecular parameters calculated for each of the chemicals in the database include the logarithm of the octanol–water partition coefficient, molar volume, and molar refractivity. For each chemical, the availability of these molecular parameter values can facilitate future QSAR studies using any of the 18 different toxicological end points measured as the biological activity of interest.

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Kannamkumarath, Sasi S., Rodolfo G. Wuilloud et Joseph A. Caruso. « Studies of Various Elements of Nutritional and Toxicological Interest Associated with Different Molecular Weight Fractions in Brazil Nuts ». Journal of Agricultural and Food Chemistry 52, n^o 19 (septembre 2004) : 5773–80. http://dx.doi.org/10.1021/jf0496649.

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Subhan, Md, Kristi Choudhury et Newton Neogi. « Advances with Molecular Nanomaterials in Industrial Manufacturing Applications ». Nanomanufacturing 1, n^o 2 (27 août 2021) : 75–97. http://dx.doi.org/10.3390/nanomanufacturing1020008.

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Molecular nanomaterials are of prodigious reputation for their uses in the numerous industries. This article highlights established industrial potential application areas for nanoparticles. The success of nanomanufacturing depends on the strong cooperation between academia and industry in order to be informed about current needs and future challenges, to design products directly translated to the industrial sector. The selection of the appropriate method, combining synthesis of nanomaterials with required properties and limited impurities as well as scalability of the technique, is of paramount importance. Varieties of molecular nanomaterials and their synthesis, characterization, and important applications are of current interest in several industries. Improved synthetic routes and advanced characterization methods will be important to advance molecular nanomaterials for their rapid translation to industries, manufacturing many useful products, and their implication in global economic development. Nanomaterials have emerging applications in almost all modern industries including construction, textile, water, aeronautics, food, medicine, environment cosmetics, machinery, oil and gas and computer. In the current review, we have chosen some leading industries world-wide that use nanomaterials. Besides the important applications of nanomaterials in almost all spheres of human life and environment, their toxicological effects must be addressed properly to utilize these applications. There are also some obstacles to a greater impact of nanotechnology in industry including its toxicological effects in human and surrounding environments and regulations of nanomaterials use. This review addresses molecular nanomaterials synthesis strategies, characterization methods developments, and their novel industrial and other relevant application fields.

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Moody, R. L., T. Vo-Dinh et W. H. Fletcher. « Investigation of Experimental Parameters for Surface-Enhanced Raman Scattering (SERS) Using Silver-Coated Microsphere Substrates ». Applied Spectroscopy 41, n^o 6 (août 1987) : 966–70. http://dx.doi.org/10.1366/0003702874447761.

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The effects of experimental parameters on surface-enhanced Raman scattering (SERS) for silver-coated microsphere substrates were investigated. The parameters included sphere size, silver thickness, and excitation wavelength. The SERS signal intensity varied as each of these parameters was changed. The potential for increasing SERS sensitivity was illustrated by the detection of benzo(a)pyrene, a molecule of environmental and toxicological interest, at a concentration well below that possible for normal Raman scattering. This work describes some optimization procedures and demonstrates the possibility for further improving SERS enhancement of these silver-coated microsphere substrates by optimizing experimental parameters.

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Hobson, David W., Stephen M. Roberts, Anna A. Shvedova, David B. Warheit, Georgia K. Hinkley et Robin C. Guy. « Applied Nanotoxicology ». International Journal of Toxicology 35, n^o 1 (janvier 2016) : 5–16. http://dx.doi.org/10.1177/1091581816628484.

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Nanomaterials, including nanoparticles and nanoobjects, are being incorporated into everyday products at an increasing rate. These products include consumer products of interest to toxicologists such as pharmaceuticals, cosmetics, food, food packaging, household products, and so on. The manufacturing of products containing or utilizing nanomaterials in their composition may also present potential toxicologic concerns in the workplace. The molecular complexity and composition of these nanomaterials are ever increasing, and the means and methods being applied to characterize and perform useful toxicologic assessments are rapidly advancing. This article includes presentations by experienced toxicologists in the nanotoxicology community who are focused on the applied aspect of the discipline toward supporting state of the art toxicologic assessments for food products and packaging, pharmaceuticals and medical devices, inhaled nanoparticle and gastrointestinal exposures, and addressing occupational safety and health issues and concerns. This symposium overview article summarizes 5 talks that were presented at the 35th Annual meeting of the American College of Toxicology on the subject of “Applied Nanotechnology.”

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Odhar, Hasanain Abdulhameed. « Molecular docking and dynamics simulation analysis of the human FXIIa with compounds from the Mcule database ». Bioinformation 19, n^o 2 (28 février 2023) : 160–66. http://dx.doi.org/10.6026/97320630019160.

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The human factor XIIa is a serine protease enzyme that is implicated in the pathological thrombosis. This coagulation factor represents an interesting molecular target to design safer antithrombotic agents without adversely influencing physiological hemostasis. Therefore, it is of interest to virtually screen the human factor XIIa crystal with millions of compounds in Mcule database in order to identify potential inhibitors. For this purpose, both molecular docking and dynamics simulation were employed to identify potential hits. Also, various predictive approaches were utilized to estimate chemical, pharmacokinetics and toxicological features for the top hits. As such, we report here that compound 4 (1‐(4‐benzylpiperazin‐1‐yl)‐2‐[5‐(3,5‐dimethylpyrazol‐1‐yl)‐1,2,3,4‐tetrazol‐2‐yl]ethanone) may be a potential ligand against the human factor XIIa for further consideration in the design and development of novel antithrombotic agents.

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Turner, Oliver C., Brian Knight, Aleksandra Zuraw, Geert Litjens et Daniel G. Rudmann. « Mini Review : The Last Mile—Opportunities and Challenges for Machine Learning in Digital Toxicologic Pathology ». Toxicologic Pathology 49, n^o 4 (16 février 2021) : 714–19. http://dx.doi.org/10.1177/0192623321990375.

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The 2019 manuscript by the Special Interest Group on Digital Pathology and Image Analysis of the Society of Toxicologic pathology suggested that a synergism between artificial intelligence (AI) and machine learning (ML) technologies and digital toxicologic pathology would improve the daily workflow and future impact of toxicologic pathologists globally. Now 2 years later, the authors of this review consider whether, in their opinion, there is any evidence that supports that thesis. Specifically, we consider the opportunities and challenges for applying ML (the study of computer algorithms that are able to learn from example data and extrapolate the learned information to unseen data) algorithms in toxicologic pathology and how regulatory bodies are navigating this rapidly evolving field. Although we see similarities with the “Last Mile” metaphor, the weight of evidence suggests that toxicologic pathologists should approach ML with an equal dose of skepticism and enthusiasm. There are increasing opportunities for impact in our field that leave the authors cautiously excited and optimistic. Toxicologic pathologists have the opportunity to critically evaluate ML applications with a “call-to-arms” mentality. Why should we be late adopters? There is ample evidence to encourage engagement, growth, and leadership in this field.

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Al Sharif, Merilin, Petko Alov, Vessela Vitcheva, Ilza Pajeva et Ivanka Tsakovska. « Modes-of-Action Related to Repeated Dose Toxicity : Tissue-Specific Biological Roles of PPARγLigand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease ». PPAR Research 2014 (2014) : 1–13. http://dx.doi.org/10.1155/2014/432647.

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Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP) of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD) are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPARγligand-dependent dysregulation as a key molecular initiating event (MIE) for this adverse effect. The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPARγ. Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPARγ-dependent prosteatotic MoA. A detailed analysis was performed regarding proteins which PPARγ-mediated expression changes had been confirmed to be prosteatotic by most experimental evidence. Two probable toxicological MoAs from PPARγligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD) concepts: (i) PPARγactivation in hepatocytes and (ii) PPARγinhibition in adipocytes. The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details.

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Pestka, J. « Toxicological mechanisms and potential health effects of deoxynivalenol and nivalenol ». World Mycotoxin Journal 3, n^o 4 (1 novembre 2010) : 323–47. http://dx.doi.org/10.3920/wmj2010.1247.

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Produced by the mould genus Fusarium, the type B trichothecenes include deoxynivalenol (DON), nivalenol (NIV) and their acetylated precursors. These mycotoxins often contaminate cereal staples, posing a potential threat to public health that is still incompletely understood. Understanding the mechanistic basis by which these toxins cause toxicity in experimental animal models will improve our ability to predict the specific thresholds for adverse human effects as well as the persistence and reversibility of these effects. Acute exposure to DON and NIV causes emesis in susceptible species such as pigs in a manner similar to that observed for certain bacterial enterotoxins. Chronic exposure to these mycotoxins at low doses causes growth retardation and immunotoxicity whereas much higher doses can interfere with reproduction and development. Pathophysiological events that precede these toxicities include altered neuroendocrine responses, upregulation of proinflammatory gene expression, interference with growth hormone signalling and disruption of gastrointestinal tract permeability. The underlying molecular mechanisms involve deregulation of protein synthesis, aberrant intracellular cell signalling, gene transactivation, mRNA stabilisation and programmed cell death. A fusion of basic and translational research is now needed to validate or refine existing risk assessments and regulatory standards for DON and NIV. From the perspective of human health translation, biomarkers have been identified that potentially make it possible to conduct epidemiological studies relating DON consumption to potential adverse human health effects. Of particular interest will be linkages to growth retardation, gastrointestinal illness and chronic autoimmune diseases. Ultimately, such knowledge can facilitate more precise science-based risk assessment and management strategies that protect consumers without reducing availability of critical food sources.

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Skaperda, Zoi, Fotios Tekos, Periklis Vardakas, Charitini Nepka et Demetrios Kouretas. « Reconceptualization of Hormetic Responses in the Frame of Redox Toxicology ». International Journal of Molecular Sciences 23, n^o 1 (21 décembre 2021) : 49. http://dx.doi.org/10.3390/ijms23010049.

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Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date.

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Manca, D., L. Ferron et J. P. Weber. « A system for toxicological screening by capillary gas chromatography with use of a drug retention index based on nitrogen-containing reference compounds. » Clinical Chemistry 35, n^o 4 (1 avril 1989) : 601–7. http://dx.doi.org/10.1093/clinchem/35.4.601.

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Abstract Capillary gas chromatography with nitrogen-specific detection allows rapid screening of numerous drugs of toxicological interest. However, for accurate identification of individual peaks, the system must be well calibrated, e.g., through the use of retention indices (RI). To overcome problems associated with the use of RI's based on homologous series determined with nitrogen-specific detectors, we have developed an RI reference system based on molecular masses and retention times of nitrogen-containing compounds. The standards chosen are easily available in highly purified form and can be detected by the unmodified nitrogen-specific detector. By using temperature programming, we can obtain a linear relationship between the molecular masses of standards and their retention times. Used in conjunction with microcomputer data handling, this screening system is rugged and reliable, operating 22 h per day. In the past two years, we have screened greater than 3000 samples (blood, serum, urine, gastric lavage) without major problems.

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Garg, Anahita, et Jetty Chung-Yung Lee. « Vitamin E : Where Are We Now in Vascular Diseases ? » Life 12, n^o 2 (18 février 2022) : 310. http://dx.doi.org/10.3390/life12020310.

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Vitamin E is one of the most popular fat-soluble vitamins in pathological research and has been under scrutiny since the 1980s as a vital dietary component of food. The antioxidant effect of vitamin E has been widely studied due to its benefits in the prevention of various cardiovascular diseases. In recent years, alternative effects of vitamin E, in terms of anti-inflammatory pathways and gene regulation, have also been of interest to researchers. This review examines the role of dietary vitamin E (α-tocopherol) as an antioxidant and bioactive molecule in promoting vascular health. While the antioxidant effect of vitamin E is well established, knowledge about its capacity as a promising regulatory molecule in the control of the vascular system is limited. The aim of this review is to discuss some of these mechanisms and summarize their role in the prevention of cardiovascular diseases (CVD). Here, we also briefly discuss foods rich in vitamin E, and deliberate some potential toxicological effects of excessive supplemental vitamin E in the body.

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Soufan, Othman, Jessica Ewald, Charles Viau, Doug Crump, Markus Hecker, Niladri Basu et Jianguo Xia. « T1000 : a reduced gene set prioritized for toxicogenomic studies ». PeerJ 7 (29 octobre 2019) : e7975. http://dx.doi.org/10.7717/peerj.7975.

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There is growing interest within regulatory agencies and toxicological research communities to develop, test, and apply new approaches, such as toxicogenomics, to more efficiently evaluate chemical hazards. Given the complexity of analyzing thousands of genes simultaneously, there is a need to identify reduced gene sets. Though several gene sets have been defined for toxicological applications, few of these were purposefully derived using toxicogenomics data. Here, we developed and applied a systematic approach to identify 1,000 genes (called Toxicogenomics-1000 or T1000) highly responsive to chemical exposures. First, a co-expression network of 11,210 genes was built by leveraging microarray data from the Open TG-GATEs program. This network was then re-weighted based on prior knowledge of their biological (KEGG, MSigDB) and toxicological (CTD) relevance. Finally, weighted correlation network analysis was applied to identify 258 gene clusters. T1000 was defined by selecting genes from each cluster that were most associated with outcome measures. For model evaluation, we compared the performance of T1000 to that of other gene sets (L1000, S1500, Genes selected by Limma, and random set) using two external datasets based on the rat model. Additionally, a smaller (T384) and a larger version (T1500) of T1000 were used for dose-response modeling to test the effect of gene set size. Our findings demonstrated that the T1000 gene set is predictive of apical outcomes across a range of conditions (e.g., in vitro and in vivo, dose-response, multiple species, tissues, and chemicals), and generally performs as well, or better than other gene sets available.

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Cheng, Tsai-Mu, Hsiu-Yi Chu, Haw-Ming Huang, Zi-Lin Li, Chiang-Ying Chen, Ya-Jung Shih, Jacqueline Whang-Peng et al. « Toxicologic Concerns with Current Medical Nanoparticles ». International Journal of Molecular Sciences 23, n^o 14 (8 juillet 2022) : 7597. http://dx.doi.org/10.3390/ijms23147597.

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Nanotechnology is one of the scientific advances in technology. Nanoparticles (NPs) are small materials ranging from 1 to 100 nm. When the shape of the supplied nanoparticles changes, the physiological response of the cells can be very different. Several characteristics of NPs such as the composition, surface chemistry, surface charge, and shape are also important parameters affecting the toxicity of nanomaterials. This review covered specific topics that address the effects of NPs on nanomedicine. Furthermore, mechanisms of different types of nanomaterial-induced cytotoxicities were described. The distributions of different NPs in organs and their adverse effects were also emphasized. This review provides insight into the scientific community interested in nano(bio)technology, nanomedicine, and nanotoxicology. The content may also be of interest to a broad range of scientists.

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Turner, Oliver C., Famke Aeffner, Dinesh S. Bangari, Wanda High, Brian Knight, Tom Forest, Brieuc Cossic et al. « Society of Toxicologic Pathology Digital Pathology and Image Analysis Special Interest Group Article* : Opinion on the Application of Artificial Intelligence and Machine Learning to Digital Toxicologic Pathology ». Toxicologic Pathology 48, n^o 2 (23 octobre 2019) : 277–94. http://dx.doi.org/10.1177/0192623319881401.

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Toxicologic pathology is transitioning from analog to digital methods. This transition seems inevitable due to a host of ongoing social and medical technological forces. Of these, artificial intelligence (AI) and in particular machine learning (ML) are globally disruptive, rapidly growing sectors of technology whose impact on the long-established field of histopathology is quickly being realized. The development of increasing numbers of algorithms, peering ever deeper into the histopathological space, has demonstrated to the scientific community that AI pathology platforms are now poised to truly impact the future of precision and personalized medicine. However, as with all great technological advances, there are implementation and adoption challenges. This review aims to define common and relevant AI and ML terminology, describe data generation and interpretation, outline current and potential future business cases, discuss validation and regulatory hurdles, and most importantly, propose how overcoming the challenges of this burgeoning technology may shape toxicologic pathology for years to come, enabling pathologists to contribute even more effectively to answering scientific questions and solving global health issues. [Box: see text]

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Soriano-Ursúa, Marvin A., Eunice D. Farfán-García et Simonetta Geninatti-Crich. « Turning Fear of Boron Toxicity into Boron-containing Drug Design ». Current Medicinal Chemistry 26, n^o 26 (22 octobre 2019) : 5005–18. http://dx.doi.org/10.2174/0929867326666190327154954.

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Background: Despite the historical employment of boron-containing compounds (BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the twentieth-century drived us towards a “boron-withdrawal” period. Fortunately, the use of boric acid for specific purposes remains, and the discovery of natural BCCs with biological action attractive for therapeutic purposes as well as the introduction of some new BCCs for clinical use has reactivated the interest in studying the properties of these BCCs. Methods: We carried out a structured search of bibliographic databases for scientific peerreviewed research literature regarding boron toxicity and linked that information to that of BCCs in drug design and development. A deductive qualitative content analysis methodology was applied to analyse the interventions and findings of the included studies using a theoretical outline. Results: This review recapitulates the following on a timeline: the boron uses in medicine, the data known about the toxicological profiles of some BCCs, the pharmacological properties of some BCCs that are employed in cancer and infectious disease therapies, and the known properties of BCCs recently introduced into clinical assays as well as the identification of their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use of new approaches taking advantage of some toxicological data to identify potent and efficient BCCs for prevention and therapy while limiting their toxic effects. Conclusion: Data for boron toxicity can be strategically used for boron-containing drug design.

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Le Trequesser, Quentin, Hervé Seznec et Marie-Hélène Delville. « Functionalized nanomaterials : their use as contrast agents in bioimaging : mono- and multimodal approaches ». Nanotechnology Reviews 2, n^o 2 (1 avril 2013) : 125–69. http://dx.doi.org/10.1515/ntrev-2012-0080.

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AbstractThe successful development of nanomaterials illustrates the considerable interest in the development of new molecular probes for medical diagnosis and imaging. Substantial progress was made in the synthesis protocol and characterization of these materials, whereas toxicological issues are sometimes incomplete. Nanoparticle-based contrast agents (CAs) tend to become efficient tools for enhancing medical diagnostics and surgery for a wide range of imaging modalities. The multimodal nanoparticles (NPs) are much more efficient than the conventional molecular-scale CAs. They provide new abilities for in vivo detection and enhanced targeting efficiencies through longer circulation times, designed clearance pathways, and multiple binding capacities. Properly protected, they can safely be used for the fabrication of various functional systems with targeting properties, reduced toxicity, and proper removal from the body. This review mainly describes the advances in the development of mono- to multimodal NPs and their in vitro and in vivo relevant biomedical applications ranging from imaging and tracking to cancer treatment. Besides the specific applications for classical imaging (magnetic resonance imaging, positron emission tomography, computed tomography, ultrasound, and photoacoustic imaging), the less common imaging techniques such as terahertz molecular imaging (THMI) or ion beam analysis (IBA) are mentioned. The perspectives on the multimodal theranostic NPs and their potential for clinical advances are also mentioned.

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Rednic, Robert, Ioana Macasoi, Iulia Pinzaru, Cristina Adriana Dehelean, Mirela-Cleopatra Tomescu, Monica Susan et Horea Feier. « Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells ». Life 12, n^o 11 (11 novembre 2022) : 1855. http://dx.doi.org/10.3390/life12111855.

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Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata, has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen’s eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved.

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Ramaiah, Lila, Lindsay Tomlinson, Niraj K. Tripathi, Laura C. Cregar, Allison Vitsky, Barbara von Beust, Valerie G. Barlow, William J. Reagan et Daniela Ennulat. « Principles for Assessing Adversity in Toxicologic Clinical Pathology ». Toxicologic Pathology 45, n^o 2 (5 janvier 2017) : 260–66. http://dx.doi.org/10.1177/0192623316681646.

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There is limited direction in the literature or regulatory guidance on determination of adversity for clinical pathology (CP) biomarkers in preclinical safety studies. Toxicologic clinical pathologists representing the American Society for Veterinary Clinical Pathology—Regulatory Affairs Committee and Society of Toxicologic Pathology—Clinical Pathology Interest Group identified principles, overall approach, and unique considerations for assessing adversity in CP data interpretation to provide a consensus opinion. Emphasized is the need for pathophysiologic context and a weight-of-evidence approach. Most CP biomarkers do not have the potential to be adverse in isolation, regardless of magnitude of change. Rather, they quantify or describe the impact of effects, provide adjunct or supportive information regarding a process or pathogenesis, and provide translational biomarkers of effect. Most often, CP changes are part of a constellation of findings that collectively are adverse. Thus, most CP changes must be interpreted in conjunction with other study findings and require contextual and integrative interpretation. Exceptions include critical CP changes without correlates that indicate a health risk in the tested species. Overall, CP changes should not be interpreted in isolation and their adversity is best addressed with an integrated approach.

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Sies, Helmut. « Findings in redox biology : From H2O2 to oxidative stress ». Journal of Biological Chemistry 295, n^o 39 (25 septembre 2020) : 13458–73. http://dx.doi.org/10.1074/jbc.x120.015651.

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My interest in biological chemistry proceeded from enzymology in vitro to the study of physiological chemistry in vivo. Investigating biological redox reactions, I identified hydrogen peroxide (H2O2) as a normal constituent of aerobic life in eukaryotic cells. This finding led to developments that recognized the essential role of H2O2 in metabolic redox control. Further research included studies on GSH, toxicological aspects (the concept of “redox cycling”), biochemical pharmacology (ebselen), nutritional biochemistry and micronutrients (selenium, carotenoids, flavonoids), and the concept of “oxidative stress.” Today, we recognize that oxidative stress is two-sided. It has its positive side in physiology and health in redox signaling, “oxidative eustress,” whereas at higher intensity, there is damage to biomolecules with potentially deleterious outcome in pathophysiology and disease, “oxidative distress.” Reflecting on these developments, it is gratifying to witness the enormous progress in redox biology brought about by the science community in recent years.

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Ibrahim, Amina M., Mahassen Ghazy, Heba El-Sayed, Rehab M. Abd El-Hameed, Rehab G. Khalil, Shereen M. Korany, Abeer S. Aloufi, Olfat A. Hammam et Mostafa Y. Morad. « Histopathological, Immunohistochemical, Biochemical, and In Silico Molecular Docking Study of Fungal-Mediated Selenium Oxide Nanoparticles on Biomphalaria alexandrina (Ehrenberg, 1831) Snails ». Microorganisms 11, n^o 3 (22 mars 2023) : 811. http://dx.doi.org/10.3390/microorganisms11030811.

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Daphnia magna and freshwater snails are used as delicate bioindicators of contaminated aquatic habitats. Due to their distinctive characteristics, selenium oxide nanoparticles (SeONPs) have received interest regarding their possible implications on aquatic environments. The current study attempted to investigate the probable mechanisms of fungal-mediated selenium nanoparticles’ ecotoxicological effects on freshwater Biomphalaria alexandrina snails and Daphnia magna. SeONPs revealed a toxicological impact on D. magna, with a half-lethal concentration (LC50) of 1.62 mg/L after 24 h and 1.08 mg/L after 48 h. Survival, fecundity, and reproductive rate were decreased in B. alexandrina snails exposed to SeONPs. Furthermore, the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were markedly elevated, while albumin and total protein levels decreased. Histopathological damage in the hermaphrodite and digestive glands was detected by light, electron microscopy, and immunohistochemistry studies. The molecular docking study revealed interactions of selenium oxide with the ALT and AST. In conclusion, B. alexandrina snails and D. magna could be employed as bioindicators of selenium nanomaterial pollution in aquatic ecosystems. This study emphasizes the possible ecological effects of releasing SeONPs into aquatic habitats, which could serve as motivation for regulatory organizations to monitor and control the use and disposal of SeONPs in industry.

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Merlot, Angelica M., Danuta S. Kalinowski, Zaklina Kovacevic, Patric J. Jansson, Sumit Sahni, Michael L. H. Huang, Darius J. R. Lane, Hiu Lok et Des R. Richardson. « Exploiting Cancer Metal Metabolism using Anti-Cancer Metal- Binding Agents ». Current Medicinal Chemistry 26, n^o 2 (14 mars 2019) : 302–22. http://dx.doi.org/10.2174/0929867324666170705120809.

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Metals are vital cellular elements necessary for multiple indispensable biological processes of living organisms, including energy transduction and cell proliferation. Interestingly, alterations in metal levels and also changes in the expression of proteins involved in metal metabolism have been demonstrated in a variety of cancers. Considering this and the important role of metals for cell growth, the development of drugs that sequester metals has become an attractive target for the development of novel anti-cancer agents. Interest in this field has surged with the design and development of new generations of chelators of the thiosemicarbazone class. These ligands have shown potent anticancer and anti-metastatic activity in vitro and in vivo. Due to their efficacy and safe toxicological assessment, some of these agents have recently entered multi-center clinical trials as therapeutics for advanced and resistant tumors. This review highlights the role and changes in homeostasis of metals in cancer and emphasizes the pre-clinical development and clinical assessment of metal ion-binding agents, namely, thiosemicarbazones, as antitumor agents.

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Paolino, Giovanni, Matteo Riccardo Di Nicola, Ignazio Avella et Santo Raffaele Mercuri. « Venomous Bites, Stings and Poisoning by European Vertebrates as an Overlooked and Emerging Medical Problem : Recognition, Clinical Aspects and Therapeutic Management ». Life 13, n^o 6 (23 mai 2023) : 1228. http://dx.doi.org/10.3390/life13061228.

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Europe presents a high number of venomous and poisonous animals able to elicit medically relevant symptoms in humans. However, since most of the accidents involving venomous or poisonous animals in Europe are unreported, their incidence and morbidity are severely overlooked. Here we provide an overview of the European vertebrate species of greatest toxicological interest, the clinical manifestations their toxins can cause, and their treatment. We report the clinical symptoms induced by envenomations and poisoning caused by reptiles, fishes, amphibians and mammals in Europe, ranging from mild, local symptoms (e.g., erythema, edema) to systemic and potentially deadly. The present work constitutes a tool for physicians to recognize envenomation/poisoning symptoms caused by the most medically relevant European vertebrates and to decide which approach is the most appropriate to treat them.

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Noga, Maciej, Justyna Milan, Adrian Frydrych et Kamil Jurowski. « Toxicological Aspects, Safety Assessment, and Green Toxicology of Silver Nanoparticles (AgNPs)—Critical Review : State of the Art ». International Journal of Molecular Sciences 24, n^o 6 (7 mars 2023) : 5133. http://dx.doi.org/10.3390/ijms24065133.

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In recent years, research on silver nanoparticles (AgNPs) has attracted considerable interest among scientists because of, among other things, their alternative application to well-known medical agents with antibacterial properties. The size of the silver nanoparticles ranges from 1 to 100 nm. In this paper, we review the progress of research on AgNPs with respect to the synthesis, applications, and toxicological safety of AgNPs, and the issue of in vivo and in vitro research on silver nanoparticles. AgNPs’ synthesis methods include physical, chemical, and biological routes, as well as “green synthesis”. The content of this article covers issues related to the disadvantages of physical and chemical methods, which are expensive and can also have toxicity. This review pays special attention to AgNP biosafety concerns, such as potential toxicity to cells, tissues, and organs.

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Medrano-Padial, Concepción, María Puerto, F. Javier Moreno, Tristan Richard, Emma Cantos-Villar et Silvia Pichardo. « In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry ». Antioxidants 8, n^o 10 (9 octobre 2019) : 467. http://dx.doi.org/10.3390/antiox8100467.

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The reduction of sulfur dioxide in wine is a consumer’s demand, considering the allergic effects that may occur in people who are sensitive to it. Stilbenes are candidates of great interest for this purpose because of their antioxidant/antimicrobial activities and health properties, and also because they are naturally found in the grapevine. In the present study, the in vitro toxicity of an extract from grapevine shoots (with a stilbene richness of 45.4%) was assessed in two human cell lines. Significant damage was observed from 30 μg/mL after 24 h, and 40 µg/mL after 48 h of exposure. Similarly, the ultrastructural study revealed a significant impairment of cell growing. The extract was able to protect cells against an induced oxidative stress at all concentrations studied. In view of the promising results, a more exhaustive toxicological assessment of the extract is needed to confirm the safety of its further use as additive in wine.

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Madden, Judith C., Vera Rogiers et Mathieu Vinken. « Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife ». Philosophical Transactions of the Royal Society B : Biological Sciences 369, n^o 1656 (19 novembre 2014) : 20130584. http://dx.doi.org/10.1098/rstb.2013.0584.

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There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called ‘adverse outcome pathway’ (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife.

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Gust, Kurt A., Qing Ji et Xiao Luo. « Example of Adverse Outcome Pathway Concept Enabling Genome-to-Phenome Discovery in Toxicology ». Integrative and Comparative Biology 60, n^o 2 (9 juin 2020) : 375–84. http://dx.doi.org/10.1093/icb/icaa064.

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Synopsis The following article represents a mini-review of an intensive 10-year progression of genome-to-phenome (G2P) discovery guided by the adverse outcome pathway (AOP) concept. This example is presented as a means to stimulate crossover of this toxicological concept to enhance G2P discovery within the broader biological sciences community. The case study demonstrates the benefits of the AOP approach for establishing causal linkages across multiple levels of biological organization ultimately linking molecular initiation (often at the genomic scale) to organism-level phenotypes of interest. The case study summarizes a US military effort to identify the mechanism(s) underlying toxicological phenotypes of lethargy and weight loss in response to nitroaromatic munitions exposures, such as 2,4,6-trinitrotoluene. Initial key discoveries are described including the toxicogenomic results that nitrotoluene exposures inhibited expression within the peroxisome proliferator activated receptor α (PPARα) pathway. We channeled the AOP concept to test the hypothesis that inhibition of PPARα signaling in nitrotoluene exposures impacted lipid metabolic processes, thus affecting systemic energy budgets, ultimately resulting in body weight loss. Results from a series of transcriptomic, proteomic, lipidomic, in vitro PPARα nuclear signaling, and PPARα knock-out investigations ultimately supported various facets of this hypothesis. Given these results, we next proceeded to develop a formalized AOP description of PPARα antagonism leading to body weight loss. This AOP was refined through intensive literature review and polished through multiple rounds of peer-review leading to final international acceptance as an Organisation for Economic Cooperation and Development-approved AOP. Briefly, that AOP identifies PPARα antagonist binding as the molecular initiating event (MIE) leading to a series of key events including inhibition of nuclear transactivation for genes controlling lipid metabolism and ketogenesis, inhibition of fatty acid beta-oxidation and ketogenesis dynamics, negative energy budget, and ultimately the adverse outcome (AO) of body-weight loss. Given that the PPARα antagonism MIE represented a reliable indicator of AO progression within the pathway, a phylogenetic analysis was conducted which indicated that PPARα amino acid relatedness generally tracked species relatedness. Additionally, PPARα amino acid relatedness analysis using the Sequence Alignment to Predict Across Species Susceptibility predicted susceptibility to the MIE across vertebrates providing context for AOP extrapolation across species. Overall, we hope this illustrative example of how the AOP concept has benefited toxicology sows a seed within the broader biological sciences community to repurpose the concept to facilitate enhanced G2P discovery in biology.

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Akermi, Sarra, Slim Smaoui, Khaoula Elhadef, Mariam Fourati, Nacim Louhichi, Moufida Chaari, Ahlem Chakchouk Mtibaa, Aissette Baanannou, Saber Masmoudi et Lotfi Mellouli. « Cupressus sempervirens Essential Oil : Exploring the Antibacterial Multitarget Mechanisms, Chemcomputational Toxicity Prediction, and Safety Assessment in Zebrafish Embryos ». Molecules 27, n^o 9 (19 avril 2022) : 2630. http://dx.doi.org/10.3390/molecules27092630.

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Nowadays, increasing interest has recently been given to the exploration of new food preservatives to avoid foodborne outbreaks or food spoilage. Likewise, new compounds that substitute the commonly used synthetic food preservatives are required to restrain the rising problem of microbial resistance. Accordingly, the present study was conducted to examine the chemical composition and the mechanism(s) of action of the Cupressus sempervirens essential oil (CSEO) against Salmonella enterica Typhimuriumand Staphyloccocus aureus. The gas chromatography analysis revealed α-pinene (38.47%) and δ-3-carene (25.14%) are the major components of the CSEO. By using computational methods, such as quantitative structure–activity relationship (QSAR), we revealed that many CSEO components had no toxic effects. Moreover, findings indicated that α-pinene, δ-3-carene and borneol, a minor compound of CSEO, could inhibit the AcrB-TolC and MepR efflux pump activity of S. enterica Typhimurium and S. aureus, respectively. In addition, our molecular docking predictions indicated the high affinity of these three compounds with active sites of bacterial DNA and RNA polymerases, pointing to plausible impairments of the pathogenic bacteria cell replication processes. As well, the safety profile was developed through the zebrafish model. The in vivo toxicological evaluation of (CSEO) exhibited a concentration-dependent manner, with a lethal concentration (LC50) equal to 6.6 µg/mL.

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Kaya, Halil İbrahim, et Ömer Şimşek. « Characterization of Pediococcus acidilactici PFC69 and Lactococcus lactis PFC77 Bacteriocins and Their Antimicrobial Activities in Tarhana Fermentation ». Microorganisms 8, n^o 7 (21 juillet 2020) : 1083. http://dx.doi.org/10.3390/microorganisms8071083.

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Tarhana is a traditional cereal product fermented by lactic acid bacteria (LAB) and yeast strains that has gained special interest recently as an infant nutrition. Tarhana contains wheat flour, yogurt, and various vegetables that might create a microbiological toxicological risk, especially for Bacillus cereus and Staphylococcus aureus. In this study, characterization of the metabolites responsible for antibacterial activity of Pediococcus acidilactici PFC69 and Lactococcus lactis PFC77 strains obtained from tarhana was performed, and antibacterial effects were detected against B. cereus ATCC 11778 and S. aureus ATCC 29213 during the fermentation. A total of 12,800 AU/mL antibacterial activity was observed for the supernatants of the PFC69 and PFC77 strains that were found to be stable at high temperature and in low pH conditions and sensitive to proteases, suggesting the antimicrobial metabolite is a bacteriocin. These bacteriocins were further purified and their molecular sizes were determined as 4.5 and 3.5 kDa, respectively. Importantly, inoculation of PFC69 and PFC77 to tarhana dough significantly decreased B. cereus ATCC 11778 and S. aureus ATCC 29213 amounts from the fifth day of fermentation compared to the control dough samples. P. acidilactici PFC69 and L. lactis PFC77 strains were concluded as bioprotective cultures for tarhana and these strains were offered for other cereal-based fermentations.

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Sharifi-Rad, Javad, Cristina Quispe, Abdelhakim Bouyahya, Naoual El Menyiy, Nasreddine El Omari, Md Shahinozzaman, Mim Ara Haque Ovey et al. « Ethnobotany, Phytochemistry, Biological Activities, and Health-Promoting Effects of the Genus Bulbophyllum ». Evidence-Based Complementary and Alternative Medicine 2022 (7 mars 2022) : 1–15. http://dx.doi.org/10.1155/2022/6727609.

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The genus Bulbophyllum is of scientific interest due to the phytochemical components and diverse biological activities found across species of the genus. Most Bulbophyllum species are epiphytic and located in habitats that range from subtropical dry forests to wet montane cloud forests. In many cultures, the genus Bulbophyllum has a religious, protective, ornamenting, cosmetic, and medicinal role. Detailed investigations into the molecular pharmacological mechanisms and numerous biological effects of Bulbophyllum spp. remain ambiguous. The review focuses on an in-depth discussion of studies containing data on phytochemistry and preclinical pharmacology. Thus, the purpose of this review was to summarize the therapeutic potential of Bulbophyllum spp. biocompounds. Data were collected from several scientific databases such as PubMed and ScienceDirect, other professional websites, and traditional medicine books to obtain the necessary information. Evidence from pharmacological studies has shown that various phytoconstituents in some Bulbophyllum species have different biological health-promoting activities such as antimicrobial, antifungal, antioxidant, anti-inflammatory, anticancer, and neuroprotective. No toxicological effects have been reported to date. Future clinical trials are needed for the clinical confirmation of biological activities proven in preclinical studies. Although orchid species are cultivated for ornamental purposes and have a wide traditional use, the novelty of this review is a summary of biological actions from preclinical studies, thus supporting ethnopharmacological data.

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Guillemette, Josée, Michel Marion, Francine Denizeau, Michel Fournier et Pauline Brousseau. « Characterization of the in vitro hepatocyte model for toxicological evaluation : repeated growth stimulation and glutathione response ». Biochemistry and Cell Biology 71, n^o 1-2 (1 janvier 1993) : 7–13. http://dx.doi.org/10.1139/o93-002.

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Hepatocytes in culture represent a useful model for investigating the effects of toxic agents on liver cells. However, further development of this model is hampered by the difficulty in promoting cell proliferation over prolonged periods and the lack of knowledge about the biochemical status of the cells relevant to the toxic response under proliferation conditions. In an effort to overcome these limitations, this work focused on the establishment of conditions to ameliorate the promotion of hepatocyte proliferation in vitro. It also examined the effects of growth stimuli on the levels of glutathione (GSH), a highly significant parameter influencing the resistance against toxic agents. In addition, albumin secretion was monitored as an indicator of liver-specific functions. Two modified L-15 media were developed: medium A for supporting cell differentiation, and medium B for promotion of proliferation. Collagen and Matrigel were used as substrata. In medium A, the time course of GSH levels was comparable for both substrata, with an initial increase followed by a plateau and then by a progressive decrease from the second to the fourth week. Hepatocytes cultured on collagen and sequentially exposed to medium B (containing epidermal growth factor ± norepinephrine) and medium A, showed repeated responsiveness to stimulation of DNA synthesis. Moreover, for cultures on collagen, a higher GSH content was observed in parallel with DNA synthesis stimulation, while albumin secretion was diminished. Although cells on Matrigel were refractory to DNA synthesis stimulation, GSH levels were still increased upon exposure to the growth factors, while under these conditions, albumin synthesis remained unaltered. These results show the possibility of expanding growth stimulus applications in hepatocyte cultures when it is of interest in cell pathology studies, such as those involving the effects of long-term exposure to xenobiotics, especially carcinogens. The results also suggest that hepatocytes subjected to a growth stimulus may have better protection against toxic injury.Key words: hepatocyte, glutathione, growth factors, long-term culture, collagen.

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Kułak-Bejda, Agnieszka, Napoleon Waszkiewicz, Grzegorz Bejda, Anna Zalewska et Mateusz Maciejczyk. « Diagnostic Value of Salivary Markers in Neuropsychiatric Disorders ». Disease Markers 2019 (2 mai 2019) : 1–6. http://dx.doi.org/10.1155/2019/4360612.

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A growing interest in the usability of saliva has been observed recently. Using saliva as a diagnostic material is possible because it contains a varied range of composites, organic and inorganic like proteins, carbohydrates, and lipids, which are secreted into saliva. Moreover, this applies to drugs and their metabolites. Saliva collection is noninvasive, and self-collection is possible. There is a lack of risk of injuries related to injection with needle, and it is generally safe. Human saliva has been successfully used, for example, in the diagnosis of many systemic diseases like cancers, autoimmunological diseases, infectious diseases (HIV, hepatitis, and malaria), and endocrinological diseases, as well as diseases of the gastrointestinal tract. Also, it is used in toxicological diagnostics, drug monitoring, and forensic medicine. The usefulness of saliva as a biological marker has also been extended to psychiatry. The specificity of mental illness and patients limits or prevents cooperation and diagnosis. In many cases, the use of saliva as a marker seems to be the most sensible choice.

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Aguirre, Shirley A., Jonathan R. Heyen, Walter Collette, Walter Bobrowski et Eileen R. Blasi. « Cardiovascular Effects in Rats following Exposure to a Receptor Tyrosine Kinase Inhibitor ». Toxicologic Pathology 38, n^o 3 (15 mars 2010) : 416–28. http://dx.doi.org/10.1177/0192623310364027.

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The receptor tyrosine kinase receptor (RTK) signaling pathway, mesenchymal-epithelial transition factor (c-Met)/hepatocyte growth factor receptor (HGFR), has been implicated in oncogenesis and is a target of interest in cancer therapy. PF-04254644 is a potent and selective inhibitor of c-Met/HGFR. Wide ligand binding profiling of PF-04254644 revealed a potentially significant interaction with phosphodiesterase (PDE) 3, and follow-up PDE enzyme activity assays confirmed PF-04254644 as a potent inhibitor of PDE3 as well as other PDEs (1, 2, 5, 10, and 11). Clinical observations, laboratory, and echocardiography parameters were recorded in Sprague-Dawley (SD) rats that received PF-04254644 oral dosing for up to seven consecutive days. Toxicological evaluations revealed myocardial degeneration as an adverse event at all tested doses. Echocardiographic evaluations revealed an increase in heart rate (HR) and contractility after the first dose with PF-04254644 and myocardial fibrosis correlated with decreased cardiac function after repeat dosing. A study in telemetry-instrumented rats substantiated that PF-04254644 induced a sustained increased HR and decreased contractility after six days of treatment. Data suggest that the decreased cardiac function and cardiotoxicity are likely due to inhibition of multiple PDEs by PF-04254644.

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Ritschar, Sven, Elisabeth Schirmer, Benedikt Hufnagl, Martin G. J. Löder, Andreas Römpp et Christian Laforsch. « Classification of target tissues of Eisenia fetida using sequential multimodal chemical analysis and machine learning ». Histochemistry and Cell Biology 157, n^o 2 (8 novembre 2021) : 127–37. http://dx.doi.org/10.1007/s00418-021-02037-1.

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AbstractAcquiring comprehensive knowledge about the uptake of pollutants, impact on tissue integrity and the effects at the molecular level in organisms is of increasing interest due to the environmental exposure to numerous contaminants. The analysis of tissues can be performed by histological examination, which is still time-consuming and restricted to target-specific staining methods. The histological approaches can be complemented with chemical imaging analysis. Chemical imaging of tissue sections is typically performed using a single imaging approach. However, for toxicological testing of environmental pollutants, a multimodal approach combined with improved data acquisition and evaluation is desirable, since it may allow for more rapid tissue characterization and give further information on ecotoxicological effects at the tissue level. Therefore, using the soil model organism Eisenia fetida as a model, we developed a sequential workflow combining Fourier transform infrared spectroscopy (FTIR) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for chemical analysis of the same tissue sections. Data analysis of the FTIR spectra via random decision forest (RDF) classification enabled the rapid identification of target tissues (e.g., digestive tissue), which are relevant from an ecotoxicological point of view. MALDI imaging analysis provided specific lipid species which are sensitive to metabolic changes and environmental stressors. Taken together, our approach provides a fast and reproducible workflow for label-free histochemical tissue analyses in E. fetida, which can be applied to other model organisms as well.

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Radice, Matteo, Andrea Durofil, Raissa Buzzi, Erika Baldini, Amaury Pérez Martínez, Laura Scalvenzi et Stefano Manfredini. « Alpha-Phellandrene and Alpha-Phellandrene-Rich Essential Oils : A Systematic Review of Biological Activities, Pharmaceutical and Food Applications ». Life 12, n^o 10 (14 octobre 2022) : 1602. http://dx.doi.org/10.3390/life12101602.

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Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July, 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword “alpha-phellandrene” in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species Anethum graveolens and Foeniculum vulgare are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene.

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Duval, Romain, Linh-Chi Bui, Cécile Mathieu, Emile Petit, Jean-Marie Dupret, Jan Cools, Fabien Guidez, Christine Chomienne et Fernando Rodrigues-Lima. « Benzene-Induced Leukemogenesis : Irreversible Inhibition of PTPN2 and Subsequent STAT1 Signaling Alteration By the Hematotoxic Metabolite Benzoquinone ». Blood 126, n^o 23 (3 décembre 2015) : 3671. http://dx.doi.org/10.1182/blood.v126.23.3671.3671.

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Abstract Benzene (BZ) is a chemical compound of industrial and toxicological interest classified as a class I human carcinogen. Environmental and occupational exposure to BZ lead to bone marrow malignancies such as leukemia. The leukemogenic effects of BZ relies on its metabolization in bone marrow cells into reactive metabolites, in particular benzoquinone (BQ) that can react with macromolecules (arylation) and/or induce oxidative stress. Although BZ is well recognized as a leukemogenic chemical, most of the key molecular and cellular mechanisms underlying its hematotoxicity are not fully understood. PTPN2 is a protein tyrosine phosphatase (PTP) mainly expressed in hematopoietic cells and playing a key role in the homeostasis of the hematopoietic system. In particular, this PTP is an important modulator of growth factors and JAK/STAT signaling pathways. Loss of function analyses in patients with mutation/deletion of the PTPN2 gene and knock-out mouse models indicate that PTPN2 acts as a tumor suppressor in haematologic disorders such as leukemia. We found that BQ, the prime hematotoxic metabolite of BZ, is an irreversible inhibitor of human PTPN2. Kinetic and biochemical analyses using purified PTPN2 indicated that the irreversible inhibition of the enzyme by BQ is mainly due to arylation of its active site cysteine. Exposure of immortalized human hematopoietic cells (Jurkat T and THP-1 lines) to BQ leads to the irreversible inhibition of endogenous PTPN2 activity with a concomitant over activation of JAK/STAT signaling pathway. Irreversible BQ-dependent inhibition of PTPN2 in cells was found to be mainly due to overoxydation of its catalytic cysteine into sulfinic and/or sulfonic forms. In Vivo experiments conducted in mice confirmed that exposure to BZ leads to irreversible inhibition of PTPN2 in bone marrow and spleen cells. Our data provide the first mecanistic evidence that irreversible inhibition of PTPN2, a tumor suppressor tyrosine phosphatase, may contribute to benzene-dependent leukemogenesis. Disclosures No relevant conflicts of interest to declare.

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Schreier, Verena N., Alex Odermatt et Frank Welle. « Migration Modeling as a Valuable Tool for Exposure Assessment and Risk Characterization of Polyethylene Terephthalate Oligomers ». Molecules 28, n^o 1 (25 décembre 2022) : 173. http://dx.doi.org/10.3390/molecules28010173.

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Polyethylene terephthalate (PET) is one of the most widely used food contact materials due to its excellent mechanical properties and recyclability. Migration of substances from PET and assessment of compliance are usually determined by experimental testing, which can be challenging depending on the migrants of interest. Low concentrations and missing reference standards, among other factors, have led to inadequate investigation of the migration potential of PET oligomers. Migration modeling can overcome such limitations and is therefore a suitable starting point for exposure and risk assessment. In this study, the activation energy-based (EA) model and the AP model were used to systematically evaluate the migration potential of 52 PET oligomers for 12 different application scenarios. Modeling parameters and conditions were evaluated to investigate their impact and relevance on the assessment of realistic exposures. Obtained results were compared with safety thresholds known from the concept of toxicological thresholds of concern. This allowed the evaluation and identification of oligomers and/or applications where migration or exposure levels may be associated with a potential risk because they exceed these safety thresholds. Overall, this study demonstrated that migration modeling can be a high-throughput, fast, flexible, and suitable approach for comprehensive exposure assessment.

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Rivas-García, Lorenzo, Alfonso López-Varela, José L. Quiles, María Montes-Bayón, Pilar Aranda, Juan Llopis et Cristina Sánchez-González. « Elucidating the Therapeutic Potential of Bis(Maltolato)OxoVanadium(IV) : The Protective Role of Copper in Cellular Metabolism ». International Journal of Molecular Sciences 24, n^o 11 (27 mai 2023) : 9367. http://dx.doi.org/10.3390/ijms24119367.

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Vanadium (V) is a trace mineral whose biological activity, role as a micronutrient, and pharmacotherapeutic applications remain unknown. Over the last years, interest in V has increased due to its potential use as an antidiabetic agent mediated by its ability to improve glycemic metabolism. However, some toxicological aspects limit its potential therapeutic application. The present study aims to evaluate the effect of the co-treatment with copper (Cu) and bis(maltolato)oxovanadium(IV) (BMOV) as a possible strategy to reduce the toxicity of BMOV. Treating hepatic cells with BMOV reduced cell viability under the present conditions, but cell viability was corrected when cells were co-incubated with BMOV and Cu. Additionally, the effect of these two minerals on nuclear and mitochondrial DNA was evaluated. Co-treatment with both metals reduced the nuclear damage caused by BMOV. Moreover, treatment with these two metals simultaneously tended to reduce the ND1/ND4 deletion of the mitochondrial DNA produced with the treatment using BMOV alone. In conclusion, these results showed that combining Cu and V could effectively reduce the toxicity associated with V and enhance its potential therapeutic applications.

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Blaškovičová, Jana, et Ján Labuda. « Effect of Triclosan and Silver Nanoparticles on DNA Damage Investigated with DNA-Based Biosensor ». Sensors 22, n^o 12 (8 juin 2022) : 4332. http://dx.doi.org/10.3390/s22124332.

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Triclosan (TCS) is a broad-spectrum antimicrobial agent widely used in personal care, healthcare, and clinical practice. One of the most important aspects of toxicological profiling of compounds is their interaction with DNA. In human cells, TCS causes a significant reduction in DNA methylation. The involvement of TCS in chromosomal aberrations, DNA damage, and strand breaks, as well as DNA damage from TCS degradation products, was reported. AgNPs share similarities with TCS in terms of antimicrobial properties, enter the body after exposure, and are used even together with TCS in oral care products. Therefore, their mutual effect on the DNA is of interest. In this study, the electrochemical behavior of TCS on a glassy carbon electrode (GCE) and the biosensor with salmon sperm dsDNA (DNA/GCE), DNA damage by TCS present in phosphate buffer solution pH 7.4 and an additional effect of the immobilized AgNP layer on such DNA damage have been investigated. Two different sizes of AgNPs (about 15 and 37 nm) were tested. Using square-wave voltammetric signals of nucleobases, the portion of survived DNA was 64% in the presence of 15 nm AgNPs compared to 55% in its absence. The protective effect of AgNPs on DNA against TCS-induced DNA damage was found.

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