Potential Mutagenic Effects Research Articles

Preparation and structural investigations of the composite containing lead oxide and graphite as reinforcements and its adsorptive and photocatalytic dye-degradation activity

Water contamination by lead (Pb+2) has attracted enormous research owing to its potential carcinogenic, mutagenic, and toxic effects. Composite membranes are highly efficient, and cost-effective adsorbents for the elimination of heavy metals from water. The present study involves the preparation, characterization, and adsorption properties of a novel (Polyvinyl chloride) PVC/PbO-graphite adsorptive composite membrane (ACM) for the effective removal of Pb+2 ions from water. Four composite membranes were fabricated using PbO-graphite as a filler (5, 10, 15, and 20 %) and PVC as a binder. The physiochemical properties such as water uptake, swelling degree, density, and porosity of the composite membrane were studied. All the mentioned properties were decreased and the adsorptive capacity of the membranes (5.54–9.01 mg/g) declined with increasing filler percentage. It was observed that an increase in the initial concentration, adsorption, time, and pH improved the removal efficiency of the membranes. Maximum adsorption was observed for 5 % filler composite at 80 ppm initial concentration of Pb+2 in 300 min time at a pH of 6. Furthermore, both Langmuir and Freundlich adsorption isotherms were applied to investigate and understand the adsorption ability of the prepared ACMs. These isotherms well explained the adsorption process with an average R2 of 0.9860 and 0.9813 respectively. But the results were best aligned with the Langmuir adsorption mechanism (average R2 = 0.9860). The ACMs were also utilized for the photodegradation of Congo red dye and the ACMs (20 %) degraded about 71 % dye within 50 min.

Chemical rules for optimization of chemical mutagenicity via matched molecular pairs analysis and machine learning methods

Chemical mutagenicity is a serious issue that needs to be addressed in early drug discovery. Over a long period of time, medicinal chemists have manually summarized a series of empirical rules for the optimization of chemical mutagenicity. However, given the rising amount of data, it is getting more difficult for medicinal chemists to identify more comprehensive chemical rules behind the biochemical data. Herein, we integrated a large Ames mutagenicity data set with 8576 compounds to derive mutagenicity transformation rules for reversing Ames mutagenicity via matched molecular pairs analysis. A well-trained consensus model with a reasonable applicability domain was constructed, which showed favorable performance in the external validation set with an accuracy of 0.815. The model was used to assess the generalizability and validity of these mutagenicity transformation rules. The results demonstrated that these rules were of great value and could provide inspiration for the structural modifications of compounds with potential mutagenic effects. We also found that the local chemical environment of the attachment points of rules was critical for successful transformation. To facilitate the use of these mutagenicity transformation rules, we integrated them into ADMETopt2 (http://lmmd.ecust.edu.cn/admetsar2/admetopt2/), a free web server for optimization of chemical ADMET properties. The above-mentioned approach would be extended to the optimization of other toxicity endpoints.Graphical

Ratio-dependent effects of photoactivated hypericin and manumycin A on their genotoxic and mutagenic potential

Natural compounds originated from plants and microorganisms and their combinations are currently being investigated as a possible treatment for several diseases including cancer. Hypericin (photodynamically-active pigment from Hypericum perforatum L.) and manumycin A (inhibitor of farnesyltransferase from Streptomyces parvulus) belong to the chemicals potentially applicable in clinical practice. In this study we evaluated potential cytotoxic (via trypan blue exclusion test), genotoxic (via DNA-topology and comet assays), and mutagenic effects (via bacterial reverse mutation test) of these compounds and their combinations considering the molecular mechanism of their action in cell-free and cellular systems. Our results did not reveal neither cytotoxic nor mutagenic activities of tested compounds and their combinations. Regarding the genotoxic potential, no damage of plasmid DNA in cell-free system was detected. On the other hand, photoactivated hypericin and manumycin A were able to induce primary DNA damage in human lymphocytes analyzed by comet assay. The possible antagonistic interactions between these two metabolites were estimated using SynergyFinder software analysis and experimental data obtained from comet assay. Our findings indicate that not only the presence of substances, but also their ratio plays an important role in resulting effects of the combined treatment in cellular system.

Perception, knowledge, practices and training regarding the risk of exposure to antineoplastic drugs in three French compounding units.

Healthcare workers are exposed to hazardous drugs such as antineoplastic drugs, which have potential carcinogenic, mutagenic and teratogenic effects. Protective measures must be taken after appropriate staff training to handle antineoplastic drugs in a safe way. The objective was to assess perception, knowledge, practices and training regarding the risk of exposure of healthcare workers in three French compounding units. This descriptive study was based on a questionnaire made of 33 questions divided into five sections related to the handling of antineoplastic drugs: perception of the risks, knowledge of the risks, protection practices, specific training and general questions. Among the 39 participants, over half considered their overall risk of exposure to antineoplastic drugs not being very low. Inhalation was known to 69.2% of them as possible route of contamination. The breakroom was identified by 28.9% of them as a place of contamination. The procedure in case of accidental exposure to antineoplastic drugs was known by 69.2%, but only half could explain it. Only 38.5% said they changed their gloves every 30 min as recommended. Barely half said that they had been trained specifically for the handling of antineoplastic drugs during an initial training. Over half wished to be informed, trained and aware of the proper handling of antineoplastic drugs. Although some of these results are encouraging, specifically when compared to the other settings where antineoplastic drugs are handled, there is still room for improvement. Efforts to build an adapted and impactful training program must pursue. Study CONTACT, ref. 19-504.

Study of the effect of the complex drug interamin on the cytogenetic stability of mice bone marrow cells

The article presents the results of a study of the potential mutagenic effects of the drug Interamin on the bone marrow of mice. Its effect on the cytogenetic stability of bone marrow cells after injection of an experimental mutagen (mitomycin C) was also studied. The antimutagenic potential of Interamin was studied relative to the reference drugs Aminoseleton and Bifeton-B. The study of the mutagenic effect of the compounds was carried out using a micronucleus test in polychromatophilic erythrocytes of the bone marrow of mice that is an assessment of the change in the frequency of micronuclei in polychromatophilic erythrocytes. The toxic effect of drugs on bone marrow cells was assessed by the change in the proportion of polychromatophilic erythrocytes relative to the number of normochromic erythrocytes. As a result of the study, no changes were found in the frequency of micronuclei in polychromatophilic erythrocytes and the percentage of cells of this type in the bone marrow of mice treated with Interamin at a conditional therapeutic and tenfold increased doses, as well as with its fivefold administration at intervals of 24 hours at a conditionally therapeutic dose. The course use of the study drugs at a therapeutic dose before the administration of mitomycin C led to a decrease in the frequency of micronuclei in polychromatophilic erythrocytes by 39.1% (p=0.002) and 47.6% (p=0.009) when using Interamin and Aminoseleton, respectively, relative to the indicators of animals, who were administered only mitomycin C. In the group treated with Biferon-B, such trend was not observed. At the same time, in animals of these groups, the proportion of polychromatophilic erythrocytes was higher by 33.3% (p=0.002) after the administration of Interamin and by 57.2% (p=0.009) after the use of Biferon-B, relative to the animals of the positive control group. The presented data indicate that the drug Interamin has no mutagenic properties, as well as the presence of antimutagenic and antitoxic effects that opens up prospects for its use as a gene protector and antitoxicant.

Assessment of mutagenicity of Boswellia serrata extract (Boswegex®) using Bacterial Reverse Mutation test method

Background: Extracted from the Indian branching tree Boswellia serrata, boswellic acids derived from the plant's resin hold promise in addressing inflammation, arthritis, and hyperlipidemia. Objective: In this study, the mutagenicity of B. serrata (Boswegex®) is evaluated. Materials and Methods: The potential genotoxic and mutagenic effects of Boswellia serrata's aqueous ethanolic extract, known as Boswegex®, were explored using a bacterial reverse mutation assay against Salmonella strains TA98, TA100, TA102, TA1535, and TA1537. Different concentrations ranging from 500 to 6000 μg/plate were tested using both Method 1 (Standard plate incorporation assay) and Method 2 (pre-incubation assay), with DMSO (Dimethyl sulfoxide) as the solvent control. The positive control, 2-aminoanthracene, was used alongside a metabolic activator (S-9 fraction). Given the prolonged use of supplements, an assessment for mutagenicity is vital. In this context, the mutagenicity of B. serrata (Boswegex®) was evaluated through the in vitro Bacterial Reverse Mutation Test, employing both the Standard Plate Incorporation Assay and the pre-incubation assay. Results: Notably, none of the mutagenic assays revealed a mutagenicity increase over background levels. Conclusion: These findings collectively indicate that Boswellia serrata (Boswegex®) does not exhibit mutagenic properties.

Cytotoxicity of Extracts from Petiveria alliacea Leaves on Yeast

Petiveria alliacea L. is a plant used in traditional medicine harboring pharmacological properties with anti-inflammatory, antinociceptive, hypoglycemiant and anesthetic activities. This study assessed the potential cytotoxic, genotoxic and mutagenic effects of ethanolic extract of P. alliacea on Saccharomyces cerevisiae strains. S. cerevisiae FF18733 (wild type) and CD138 (ogg1) strains were exposed to fractioned ethanolic extracts of P. alliacea in different concentrations. Three experimental assays were performed: cellular inactivation, mutagenesis (canavanine resistance system) and loss of mitochondrial function (petites colonies). The chemical analyses revealed a rich extract with phenolic compounds such as protocatechuic acid, cinnamic and catechin epicatechin. A decreased cell viability in wild-type and ogg1 strains was demonstrated. All fractions of the extract exerted a mutagenic effect on the ogg1 strain. Only ethyl acetate and n-butanol fractions increased the rate of petites colonies in the ogg1 strain, but not in the wild-type strain. The results indicate that fractions of mid-polarity of the ethanolic extract, at the studied concentrations, can induce mutagenicity mediated by oxidative lesions in the mitochondrial and genomic genomes of the ogg1-deficient S. cerevisiae strain. These findings indicate that the lesions caused by the fractions of P. alliacea ethanolic extract can be mediated by reactive oxygen species and can reach multiple molecular targets to exert their toxicity.

Anthraquinones: Genotoxic until Proven Otherwise? A Study on a Substance-Based Medical Device to Implement Available Data for a Correct Risk Assessment.

A genotoxicological study was carried out on a substance-based medical device (SMD) containing anthraquinones in order to evaluate its potential mutagenic effect. The “In Vitro Mammalian Cell Micronucleus Test” was performed on human TK6 cells by flow cytometry. Cultures were treated with concentrations of SMD tested in the range of 0–2 mg/mL for short treatment time (3 h) both in the absence and presence of an exogenous metabolic activation system, followed by a recovery period in fresh medium (23 h) and for extended treatment time (26 h) without an exogenous metabolic activation system. At the end of both treatment times, cytotoxicity, cytostasis, apoptosis and micronuclei (MNi) frequency were analysed in treated cultures and then compared with those measured in concurrent negative control cultures. The SMD did not induce a statistically significant increase MNi frequency under any of experimental conditions tested. The negative outcome shows that the SMD is non-mutagenic in terms of its ability to induce chromosomal aberrations both in the absence and presence of an exogenous metabolic activation system. The study ended by analyzing intracellular ROS levels to exclude the pro-oxidant ability, typically linked to DNA damage. On the contrary, our results demonstrated the ability the SMD to counteract oxidative stress.

VenomPred: A Machine Learning Based Platform for Molecular Toxicity Predictions.

The use of in silico toxicity prediction methods plays an important role in the selection of lead compounds and in ADMET studies since in vitro and in vivo methods are often limited by ethics, time, budget and other resources. In this context, we present our new web tool VenomPred, a user-friendly platform for evaluating the potential mutagenic, hepatotoxic, carcinogenic and estrogenic effects of small molecules. VenomPred platform employs several in-house Machine Learning (ML) models developed with datasets derived from VEGA QSAR, a software that includes a comprehensive collection of different toxicity models and has been used as a reference for building and evaluating our ML models. The results showed that our models achieved equal or better performance than those obtained with the reference models included in VEGA QSAR. In order to improve the predictive performance of our platform, we adopted a consensus approach combining the results of different ML models, which was able to predict chemical toxicity better than the single models. This improved method was thus implemented in the VenomPred platform, a freely accessible webserver that takes the SMILES (Simplified Molecular-Input Line-Entry System) strings of the compounds as input and sends the prediction results providing a probability score about their potential toxicity.

Hepatotoxicity and Mutagenicity assessment during chronic in vivo exposure to aqueous extracts from Peperomia pellucida.

Studies on herbal medicine have exposed some toxic effects on humans. Peperomia pellucida (L.) HBK (P. pellucida) is one of the herbal medicines recommended as an alternative to synthetic medicine for diseases. Studies exist on the pharmacological activities of P. pellucida extracts, but studies on the potential hepatotoxic and mutagenic effects of subchronic administration of P. pellucida aqueous extracts, which is very important knowledge when we venture into alternative medicine, are lacking. In this study, two concentrations (60 mg/kg and 30 mg/kg) of P. pellucida aqueous extracts - decoction and freeze-dried extracts -were administered in vivo to BALB/c mice for nine (9) weeks. Significant differences were observed between the 60 mg/kg freeze-dried extract and the control in terms of mice weight and micronucleus frequency at 7-8 weeks of treatment. Also, no significant differences were found between groups in serum transaminases levels. Generally, there is no sufficient evidence to show that subchronic exposure to P. pellucida aqueous extracts is hepatotoxic though 60 mg/kg concentration may be mutagenic. This study suggests that although the herbal medicine is safe for prolonged consumption, users are advised to take precautions and moderations of its use due to the possibility of potential mutagenic effects.

EVALUATION OF THE MUTAGENIC EFFECT OF THE DRUG SUBMASTIN-KRS

In this research, we studied the potential mutagenic and toxic effects of the drug Submastin-KRS, which contains a mixture of species-specific bovine recombinant cytokines and vitamin A as active ingredients, on the body of white laboratory outbred mice (n=48). The animals were divided into 8 groups, 6 individuals in each one. A single injection of Submastin-KRS at a therapeutic and high dose (1/10 of LD50) did not lead to a statistically significant increase in the frequency of polymorphonuclear erythrocytes (PCE) with micronuclei and a decrease in the proportion of PCE in the bone marrow of the mice. The combined administration of Submastin-KRS and experimental mutagens (dioxidin, mitomycin C) it also caused neither potentiation of mutagenic activity nor a decrease in the frequency of PCE with micronuclei. Fourfold administration of Submastin-KRS at a high dose with an interval of 24 hours before the injection of mitomycin C had an antitoxic effect that was expressed in a statistically significant increase in the proportion of PCE in the bone marrow, relative to mice that received only mitomycin C. A similar administration of dioxidine together with Submastin-KRS did not lead to differences in the proportion of PCE relative to this indicator with the introduction of dioxidine alone. Thus, Submastin-KRS showed no mutagenic and toxic properties in relation to mouse bone marrow cells and also had an antitoxic effect in mitomycin-induced suppression of hematopoiesis that may serve as the evidence of its safety.

Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection

BackgroundSARS-CoV-2 infection or COVID-19 is a major global public health issue that requires urgent attention in terms of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19. PurposeThe study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID-19. MethodsHomology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool. ResultsThree compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin. ConclusionThis study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19.

Environmental Risk Characterization of an Antiretroviral (ARV) Lamivudine in Ecosystems.

Antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) and other viral infections are among the emerging contaminants considered for ecological risk assessment. These compounds have been reported to be widely distributed in water bodies and other aquatic environments, while data concerning the risk they may pose to unintended non-target species in a different ecosystem (environment) is scanty. In South Africa and other developing countries, lamivudine is one of the common antiretrovirals applied. Despite this, little is known about its environmental impacts as an emerging contaminant. The present study employed a battery of ecotoxicity bioassays to assess the environmental threat lamivudine poses to aquatic fauna and flora. Daphnia magna (filter feeders), the Ames bacterial mutagenicity test, Lactuca sativa (lettuce) germination test, and the Allium cepa root tip assay were conducted, testing lamivudine at two concentrations (10 and 100 µg/L), with environmental relevance. The Daphnia magna toxicity test revealed a statistically significant response (p << 0.05) with a mortality rate of 85% on exposure to 100 µg/L lamivudine in freshwater, which increased to 100% at 48-h exposure. At lower concentrations of 10 µg/L lamivudine, 90% and 55% survival rates were observed at 24 h and 48 h, respectively. No potential mutagenic effects were observed from the Ames test at both concentrations of lamivudine. Allium cepa bioassays revealed a noticeable adverse impact on the root lengths on exposure to 100 µg/L lamivudine. This impact was further investigated through microscopic examination, revealing some chromosomal aberration in the exposed Allium cepa root tips. The Lactuca sativa bioassay showed a slight adverse impact on both the germination rate of the seeds and their respective hypocotyl lengths compared to the control. Overall, this indicates that lamivudine poses an ecological health risk at different trophic levels, to both flora and fauna, at concentrations previously found in the environment.

Evaluation of the genotoxic, mutagenic, and histopathological hepatic effects of polyoxyethylene amine (POEA) and glyphosate on Dendropsophus minutus tadpoles

Herbicides improve the productivity of a monoculture by eliminating weeds, although they may also be toxic and have negative effects on non-target organisms, such as amphibians. The present study evaluated the genotoxic, mutagenic, and histopathological hepatic responses of Dendropsophus minutus tadpoles to acute exposure (96 h) to the herbicide glyphosate (GLY, 65, 130, 260 and 520 μg/L) and the surfactant polyoxyethylene amine (POEA, 1.25, 2.5, 5 and 10 μg/L). On average, 174 % more genomic damage was observed in the tadpoles exposed to all concentrations of POEA in comparison with the control, while up to seven times more micronuclei were recorded, on average, at a concentration of 5 μg/L of POEA. All the individuals exposed to 10 μg/L of POEA died. The tadpoles exposed to GLY presented 165 % more DNA damage than the control, on average, at the highest concentrations (260 and 520 μg/L), and up to six times more micronuclei at 520 μg/L. The Erythrocyte Nuclear Abnormality test (ENA) detected a relatively high frequency of cells with lobed nuclei in the tadpoles expose to POEA at 5 μg/L and binucleated cells in those exposed to GLY at 520 μg/L. The hepatic histopathological observations revealed several types of lesions in the tadpoles exposed to both GLY and POEA. Overall, then, the results of the study indicate that both GLY and POEA have potential genotoxic, mutagenic, and hepatotoxic effects in D. minutus tadpoles. We emphasize the need for further studies to monitor the amphibian populations, such as those of D. minutus, which breed in aquatic environments associated with agricultural areas. The release of pollutants into natural habitats may have significant long-term impacts on the survival of anuran tadpoles.

Sub-chronic exposure to PhIP induces oxidative damage and DNA damage, and disrupts the amino acid metabolism in the colons of Wistar rats

Heterocyclic amines (HCAs) are a group of mutagenic compounds produced during thermal processing of protein-rich foods. One of the most abundant HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has potential carcinogenic and mutagenic effects on human organs, especially the colon. This study aimed to explore the toxic effects of PhIP on amino acid metabolism in the colon of Wistar rats using RNA-seq and LC-MS/MS. Exposure to PhIP for 4 weeks induced oxidative damage and DNA damage in the colons, and disrupted the expression of related genes involved in tryptophan metabolism, beta(β)-alanine metabolism, valine, leucine, and isoleucine degradation, and glutathione metabolic pathways. Moreover, the levels of fecal metabolites related to amino acid metabolism were affected by PhIP. Cumulatively, these results indicate that PhIP can induce colonic oxidative injury and disorders related to amino acid metabolism, thereby providing a new theoretical basis for the study of PhIP toxicity.

In-utero exposure to zidovudine-containing antiretroviral therapy and clonal hematopoiesis in HIV-exposed uninfected newborns.

Zidovudine (ZDV) has been extensively used in pregnant women to prevent vertical transmission of HIV but few studies have evaluated potential mutagenic effects of ZDV during fetal development. Our study investigated clonal hematopoiesis in HIV-exposed uninfected (HEU) newborns, 94 of whom were ZDV-exposed and 91 antiretroviral therapy (ART)-unexposed and matched for potential confounding factors. Utilizing high depth sequencing and genotyping arrays, we comprehensively examined blood samples collected during the first week after birth for potential clonal hematopoiesis associated with fetal ZDV exposure, including clonal single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural copy number or copy neutral alterations. We observed no statistically significant difference in the number of SNVs and indels per person in ZDV-exposed children (adjusted ratio [95% confidence interval, CI] for expected number of mutations = 0.79 [0.50--1.22], P = 0.3), and no difference in the number of large structural alterations. Mutations in common clonal hematopoiesis driver genes were not found in the study population. Mutational signature analyses on SNVs detected no novel signatures unique to the ZDV-exposed children and the mutational profiles were similar between the two groups. Our results suggest that clonal hematopoiesis at levels detectable in our study is not strongly influenced by in-utero ZDV exposure; however, additional follow-up studies are needed to further evaluate the safety and potential long-term impacts of in-utero ZDV exposure in HEU children as well as better investigate genomic aberrations occurring late in pregnancy.

Deuterium-depletion has no significant impact on the mutation rate of Escherichia coli, deuterium abundance therefore has a probabilistic, not deterministic effect on spontaneous mutagenesis.

Deuterium (D), the second most abundant isotope of hydrogen is present in natural waters at an approximate concentration of 145-155 ppm (ca. 1.5E-4 atom/atom). D is known to influence various biological processes due to its physical and chemical properties, which significantly differ from those of hydrogen. For example, increasing D-concentration to >1000-fold above its natural abundance has been shown to increase the frequency of genetic mutations in several species. An interesting deterministic hypothesis, formulated with the intent of explaining the mechanism of D-mutagenicity is based on the calculation that the theoretical probability of base pairs to comprise two adjacent D-bridges instead of H-bridges is 2.3E-8, which is equal to the mutation rate of certain species. To experimentally challenge this hypothesis, and to infer the mutagenicity of D present at natural concentrations, we investigated the effect of a nearly 100-fold reduction of D concentration on the bacterial mutation rate. Using fluctuation tests, we measured the mutation rate of three Escherichia coli genes (cycA, ackA and galK) in media containing D at either <2 ppm or 150 ppm concentrations. Out of 15 pair-wise fluctuation analyses, nine indicated a significant decrease, while three marked the significant increase of the mutation/culture value upon D-depletion. Overall, growth in D-depleted minimal medium led to a geometric mean of 0.663-fold (95% confidence interval: 0.483-0.911) change in the mutation rate. This falls nowhere near the expected 10,000-fold reduction, indicating that in our bacterial systems, the effect of D abundance on the formation of point mutations is not deterministic. In addition, the combined results did not display a statistically significant change in the mutation/culture value, the mutation rate or the mutant frequency upon D-depletion. The potential mutagenic effect of D present at natural concentrations on E. coli is therefore below the limit of detection using the indicated methods.

Comparative Evaluation of Mineral Trioxide Aggregate Pulpotomy and Laser-Assisted Mineral Trioxide Aggregate Pulpotomy: An Original Research Article.

Context and Aim:Formocresol has been used as the material of choice (gold standard) for pulpotomy procedures because of the ease of use but was discouraged due to its potential immune sensitization and mutagenic effects. Laser irradiation was first applied for pulpotomy procedure in the year 1985. Recently, diode lasers have been used for pulpotomy in primary teeth and have shown clinical success rates comparable to formocresol. The present in vivo study was carried out to compare the clinical and radiographic success rates of mineral trioxide aggregate (MTA) pulpotomy and diode laser-assisted pulpotomy in human primary molars.Materials and Methods:The present study was a randomized clinical trial in design wherein 40 primary teeth requiring pulpotomy treatment which met the selection criteria (clinical and radiographic) were divided into two groups, Group 1 (n = 20) wherein the pulpotomy was performed with MTA alone and Group 2 (n = 20) wherein laser-assisted pulpotomy was performed with MTA (L-MTA). The patients were recalled after 3, 6, and 9 months, respectively and evaluated clinically and radiographically.Statistical Analysis Used:The data were analyzed using the Statistical Package for the Social Sciences (SPSS) Version 22 (IBM corporation, Washington DC, United States). Descriptive statistics were used to analyze the data while the Pearson's correlation coefficient test was used to analyze the statistical correlation between the overall success rates observed in the clinical and radiographic findings of both the groups. P < 0.05 was considered statistically significant.Results:The clinical success rate in the MTA group was 90%, 84.21%, and 88.23% at 3, 6, and 9 months, respectively, with no clinical signs or, symptoms reported at the said follow-up visits while the radiographic success rate was found to be 85%, 84.21%, and 82.3%, respectively. On the contrary, the clinical success rate in the L-MTA group was found to be 95%, 94.74%, and 94.44% at 3, 6, and 9, months, respectively with the radiographic success rate reported being 90%, 89.47%, and 88.89%, respectively.Conclusion:The combination of diode laser and MTA yielded better clinical and radiographic success rates over the pulpotomy procedures done with the help of MTA alone, thereby, concluding that lasers may be considered as adjuvant alternatives for vital pulp therapy on human primary teeth.

Comparative UHPLC-Q-Orbitrap HRMS-Based Metabolomics Unveils Biochemical Changes of Black Garlic during Aging Process.

Aged black garlic (BG) is a functional food in global markets; however, very few studies have ventured into comprehensive profiling of BG metabolomes during the aging process. Herein, we exploited UHPLC-Orbitrap HRMS for a comparative metabolomics analysis. During the heat treatment, organosulfur compounds such as allicin, diallyl disulfide, ajoene, S-allyl-l-cysteine (SAC), and γ-glutamyl-SAC were downregulated. Plenty of glycerophospholipids together with shikimate, aromatic amino acids, and vitamin B6 vitamers were significantly augmented; tryptophan was however consumed to generate downstream products manifested in nicotinate metabolism and aminobenzoate degradation. These secondary metabolites serve as signaling mediators or protectants against extreme thermal exposure. Besides, Heyns compounds and Amadori-rearrangement byproducts with potential mutagenic effects were concentrated. Together, our findings expand the known metabolome space of BG processing and better elucidate the reactivities of the key metabolites. We provide in-depth insights into the biochemical changes of BG that enable further functional or toxicological investigations of this popular food.

Co-exposure of iron oxide nanoparticles and glyphosate-based herbicide induces DNA damage and mutagenic effects in the guppy (Poecilia reticulata)

Iron oxide nanoparticles (IONPs) have been tested to remediate aquatic environments polluted by chemicals, such as pesticides. However, their interactive effects on aquatic organisms remain unknown. This study aimed to investigate the genotoxicity and mutagenicity of co-exposure of IONPs (γ-Fe2O3 NPs) and glyphosate-based herbicide (GBH) in the fish Poecilia reticulata. Thus, fish were exposed to citrate-functionalized γ-Fe2O3 NPs (0.3 mg L−1; 5.44 nm) alone or co-exposed to γ-Fe2O3 NPs (0.3 mg L−1) and GBH (65 and 130 μg of glyphosate L−1) during 14 and 21 days. The genotoxicity (DNA damage) was analyzed by comet assay, while the mutagenicity evaluated by micronucleus test (MN test) and erythrocyte nuclear abnormalities (ENA) frequency. The co-exposure induced clastogenic (DNA damage) and aneugenic (nuclear alterations) effects on guppies in a time-dependent pattern. Fish co-exposed to NPs and GBH (130 μg glyphosate L−1) showed high DNA damage when compared to NPs alone and control group, indicating synergic effects after 21 days of exposure. However, mutagenic effects (ENA) were observed in the exposure groups after 14 and 21 days. Results showed the potential genotoxic and mutagenic effects of maghemite NPs and GBH co-exposure to freshwater fish. The transformation and interaction of iron oxide nanoparticles with other pollutants, as herbicides, in the aquatic systems are critical factors in the environmental risk assessment of metal-based NPs.