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To evaluate the effectiveness of photobiomodulation (PBM) in conjunction with an aerobic exercise program (AEP) on the level of pain and quality of life of women with fibromyalgia (FM). METHODS: A double-blinded randomized controlled trial in which 51 participants with FM were allocated into 4 groups: control group (CG) (n = 12); active PBM group (APG) (n = 12); AEP and placebo PBM group (EPPG) (n = 13); AEP and active PBM group (EAPG) (n = 14). AEP was performed on an ergometric bicycle; and a PBM (with an increase dosage regime) [20 J, 32 J and 40 J] was applied using a cluster device. Both interventions were performed twice a week for 12 weeks. A mixed generalized model analysis was performed, evaluating the time (initial and final) and group (EAPG, EPPG, APG and CG) interaction. All analyses were based on intent-to-treat for a significance level of p ≤ 0.05. RESULTS: The intra-group analysis demonstrated that all treated groups presented a significant improvement in the level of pain and quality of life comparing the initial and final evaluation (p < 0.05). Values for SF-36 and 6-minute walk test increased significant in intragroup analysis for EPPG comparing the initial and final evaluation. No intergroup differences were observed. CONCLUSIONS: Both exercised and PBM irradiated volunteers present improvements in the variables analyzed. However, further studies should be performed, with other PBM parameters to determine the best regime of irradiation to optimize the positive effects of physical exercises in FM patients.
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Exercício Físico , Fibromialgia , Terapia com Luz de Baixa Intensidade , Qualidade de Vida , Humanos , Feminino , Fibromialgia/radioterapia , Fibromialgia/terapia , Fibromialgia/psicologia , Fibromialgia/fisiopatologia , Terapia com Luz de Baixa Intensidade/métodos , Método Duplo-Cego , Adulto , Pessoa de Meia-Idade , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Medição da Dor , Resultado do Tratamento , Dor/radioterapia , Dor/etiologiaRESUMO
The present systematic review (SR) aims to evaluate manuscripts in order to help further elucidate the following question: is the micronucleus assay (MA) also a useful marker in gingiva, tongue, and palate for evaluating cytogenetic damage in vivo? A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to December 2023. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CIs) were established. Full manuscripts from 34 studies were carefully selected and reviewed in this setting. Our results demonstrate that the MA may be a useful biomarker of gingival tissue damage in vivo, and this tissue could be a useful alternative to the buccal mucosa. The meta-analysis analyzing the different sites regardless of the deleterious factor studied, the buccal mucosa (SMD = 0.69, 95% CI, - 0.49 to 1.88, p = 0.25) and gingiva (SMD = 0.31, 95% CI, - 0.11 to 0.72, p = 0.15), showed similar results and different outcome for the tongue (SMD = 1.19, 95% CI, 0.47 to 1.91, p = 0.001). In summary, our conclusion suggests that the MA can be a useful marker for detecting DNA damage in gingiva in vivo and that this tissue could be effective site for smearing.
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Steroids stand for a class of hormones (natural and synthetic) known to be helpful for a number of disorders. Despite the aforementioned beneficial effects of using these hormones, anabolic-androgenic steroids (AAS) are also widely abused in a non-therapeutic manner for muscle-building and strength-increasing properties that may lead to genotoxicity in different tissues. The present study aims to understand whether genotoxicity may be a suitable biomarker for AAS exposure in vivo in both experimental animal and human studies. All studies published in PubMed/Medline, Scopus, and Web of Science electronic databases that presented data on DNA damage caused by AAS were analyzed. A total of 15 articles were included in this study, and after thoroughly reviewing the studies, a total of 8 articles were classified as Strong, 6 were classified as Moderate, and only 1 was classified as Weak, totaling 14 studies being considered either Strong or Moderate. This classification makes it possible to consider the present findings as reliable. The meta-analysis data revealed a statistically significant difference in Wistar rat testis cells with AAS compared to control for tail length and % tail DNA (p < 0.001), so that the selected articles were considered homogeneous and the I2 of 0% indicated low heterogeneity. In summary, genotoxicity can be considered a suitable biomarker for monitoring AAS exposure as a result of DNA breakage and oxidative DNA damage.
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Benzene is used worldwide as a major raw material in a number of industrial processes and also a potent airborne pollutant emitted from traffic exhaust fume. The present systematic review aimed to identify potential associations between genetic polymorphisms and occupational benzene-induced genotoxicity. For this purpose, a total of 22 selected studies were carefully analysed. Our results revealed a positive relation between gene polymorphism and genotoxicity in individuals exposed to benzene, since 17 studies (out of 22) observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes influencing, therefore, individuals' susceptibility to genomic damage induced by benzene. In other words, individuals with some genotypes may show increase or decrease DNA damage and/or higher or lower DNA-repair potential. As for the quality assessment, 17 studies (out of 22) were categorized as Strong or Moderate and, therefore, we consider our findings to be trustworthy. Taken together, such findings are consistent with the notion that benzene induces genotoxicity in mammalian cells being strongly dependent on the genetic polymorphism. Certainly, such findings are important for clarifying the role of biomarkers related to genotoxicity in human biomonitoring studies.
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Benzeno , Dano ao DNA , Exposição Ocupacional , Polimorfismo Genético , Humanos , Benzeno/toxicidade , Exposição Ocupacional/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Poluentes Ocupacionais do Ar/toxicidade , Mutagênicos/toxicidadeRESUMO
In a world with a rising use of pesticides, these chemicals, although designed to effectively control pests, pose potential threats to the environment and non-target organisms, including humans. Thus, this systematic review aims to investigate a possible association between genetic polymorphisms and susceptibility and genotoxicity in individuals occupationally exposed to pesticides. This review was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A total of 14 carefully selected studies were thoroughly analyzed by two reviewers, who assigned scores based on previously set evaluation criteria. This study classified over half of the chosen studies as having moderate or strong quality, observing a correlation between certain genetic polymorphisms involved in xenobiotic metabolism and genotoxicity in workers exposed to pesticides. Results suggest that the genes associated with xenobiotic metabolism play a substantial role in determining individuals' susceptibility to genomic damage due to pesticide exposure, affecting both their peripheral blood and oral mucosa. This implies that individuals with specific genotypes may experience increased or decreased levels of DNA damage when exposed to these chemicals.
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Exposição Ocupacional , Praguicidas , Humanos , Praguicidas/toxicidade , Exposição Ocupacional/efeitos adversos , Xenobióticos , Polimorfismo Genético , Dano ao DNARESUMO
This study aimed to evaluate the scientific literature on the micronucleus assay in nasal mucosa as an appropriate method for evaluating genotoxicity caused by chemical agents. According to the PRISMA guidelines, only in vivo human studies with micronucleus assays using nasal cells were considered. Reviews, case reports, editorials, letters to the editor, and articles not written in English were excluded. The following scientific databases/search engines were used: PubMed/MEDLINE, Scopus, and Web of Science. Results: This review included 13 studies. Four articles detected no statistical significance regarding the frequency of micronuclei while nine articles showed an increase in micronuclei in nasal cells. In the qualitative analysis, two articles were considered strong, eight were moderate and three were weak. The micronucleus assay using nasal mucosa cells is a sensitive and effective technique for assessing DNA damage and an appropriate method for monitoring humans continuously exposed to chemicals.
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Mutagênicos , Mucosa Nasal , Humanos , Testes para Micronúcleos/métodos , Mutagênicos/toxicidade , Dano ao DNARESUMO
The goal of this study was to perform systematic review (SR) to investigate the scientific literature regarding the genotoxicity effects of fluoride exposure (FE). The search of databases used for this study was PubMed/Medline, SCOPUS and Web of Science. The quality of included studies was assessed using the EPHPP (Effective Public Health Practice Project). A total of 20 potentially relevant studies were selected for evaluating the genotoxicity induced by fluoride. Few studies have revealed that FE induces genotoxicity. A total of 14 studies demonstrated negative results whereas 6 studies did not. After reviewing the twenty studies, 1 was classified as weak, 10 were considered moderate and 9 were considered strong, according to the EPHPP. Taken together, it has been established that genotoxicity of fluoride is limited.
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Dano ao DNA , Fluoretos , Fluoretos/toxicidade , Bases de Dados Factuais , Ensaio CometaRESUMO
BACKGROUND: Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the biotechnological potential to develop novel drugs. AIMS: Therefore, the aim of this study was to perform a systematic review to provide an overview of the anti-inflammatory substances isolated from marine sponges with therapeutic potential. METHODS: This systematic review was performed on the Embase, PubMed, Scopus and Web of Science electronic databases. In total, 613 were found, but 340 duplicate studies were excluded, only 100 manuscripts were eligible, and 83 were included. RESULTS: The results were based on in vivo and in vitro assays, and the anti-inflammatory effects of 251 bioactive compounds extracted from marine sponges were investigated. Their anti-inflammatory activities include inhibition of pro-inflammatory mediators, such as tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), nitrite or nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), prostaglandin E2 (PGE2), phospholipase A2 (PLA2), nuclear transcription factor-kappa B (NF-κB), leukotriene B4 (LTB4), cyclooxygenase- 1 (COX-1), and superoxide radicals. CONCLUSION: In conclusion, data suggest (approximately 98% of articles) that substances obtained from marine sponges may be promising for the development of novel anti-inflammatory drugs for the treatment of different pathological conditions.
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NF-kappa B , Poríferos , Animais , NF-kappa B/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Poríferos/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo , Óxido Nítrico/metabolismoRESUMO
The aim of this systematic review was to evaluate published papers regarding the micronucleus assay in oral mucosal cells of patients undergoing orthodontic therapy (OT). A search of the scientific literature was made in the PubMed, Scopus, and Web of Science databases for all data published until November, 2021 using the combination of the following keywords: "fixed orthodontic therapy," "genetic damage", "DNA damage," "genotoxicity", "mutagenicity", "buccal cells", "oral mucosa cells," and "micronucleus assay". The systematic review was designed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Nine studies were retrieved. Some authors demonstrated that OT induces cytogenetic damage in oral mucosal cells. Out of the nine studies included, two were classified as strong, five as moderate, and two as weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed no relationship between mutagenicity in oral cells and OT in different months of treatment. At one month, the SMD = 0.65 and p = 0.08; after three months of OT, the SMD = 1.21 and p = 0.07; and after six months of OT, the SMD = 0.56 and p = 0.11. In the analyzed months of OT, I2 values were >75%, indicating high heterogeneity. In summary, this review was not able to demonstrate that OT induces genetic damage in oral cells. The study is important for the protection of patients undergoing fixed OT, given that mutagenesis participates in the multi-step process of carcinogenesis.
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Dano ao DNA , Mucosa Bucal , Humanos , Testes para MicronúcleosRESUMO
Placental Glutathione S-Transferase (GST-P) can be considered a useful marker of not only of preneoplastic lesion in rat hepatocarcinogenesis and hamster pancreatic carcinogen but also as a potential marker for premalignant and malignant lesions in cases of buccal pouch mucosa. In this context, the aim of this review is to elucidate the following question whether the GST-P is a suitable biomarker for oral carcinogenesis. A total of 16 studies were carefully selected. Our results demonstrate that GST-P expression is a useful and coherent marker for oral carcinogenesis. Regarding the samples, most studies evaluated hamsters, two evaluated GST-P expression in rats and three evaluated GST-P expression in human cells. All studies demonstrated positive findings allowing us to consider such studies reliable. In summary, our conclusion is that GST-P can be a suitable biomarker for oral carcinogenesis.
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Biomarcadores Tumorais , Carcinogênese , Glutationa Transferase , Animais , Cricetinae , Humanos , Ratos , CarcinógenosRESUMO
Marine biodiversity has emerged as a very promising resource of bioactive compounds and secondary metabolites from different sea organisms. The sponge's secondary metabolites demonstrated various bioactivities and potential pharmacological properties. This systematic review of the literature focuses on the advances achieved in the antioxidant potential of marine sponges in vitro. The review was performed in accordance with PRISMA guidelines. The main inclusion criterion for analysis was articles with identification of compounds from terpene classes that demonstrate antioxidant activity in vitro. Searching in three different databases, two hundred articles were selected. After screening abstracts, titles and evaluating for eligibility of manuscripts 14 articles were included. The most performed analyzes to detect antioxidant activity were scavenging activity 2,2-diphenyl-1-picrylhydrazyl (DPPH) and measurement of intracellular reactive oxygen species (ROS). It was possible to identify 17 compounds of the terpene class with pronounced antioxidant activity in vitro. Scientific evidence of the studies included in this review was accessed by the GRADE analysis. Terpenes play an important ecological role, moreover these molecules have a pharmaceutical and industrial application.
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Photobiomodulation (PBM) has therapeutic effects on wound healing, diabetic microangiopathy, and retinopathy. However, little is known about the use of PBM for the treatment of diabetes mellitus (DM). In this context, we aimed to evaluate the effects of PBM on pancreas morphology and insulin and glucose tolerance in an experimental model of DM. Thus, DM was induced by streptozotocin (STZ) (60 mg/kg). Subsequently, the rats were treated with PBM (808 nm and 30 J/cm2 ). After euthanasia, morphometric parameters and immunoreactivity for insulin and 8-OHdG were evaluated in the pancreas. The results showed that treated animals had higher values of body mass and higher values in the number of beta cells in the pancreas. In conclusion, PBM resulted in decreased weight loss in STZ-induced diabetic rats and presented a stimulatory effect on the pancreas of the treated animals, highlighting the promising effects of this therapy in the clinical condition of DM.
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Diabetes Mellitus Experimental , Insulinas , Terapia com Luz de Baixa Intensidade , Ratos , Animais , Ratos Wistar , Terapia com Luz de Baixa Intensidade/métodos , Pâncreas , Homeostase , Insulinas/uso terapêutico , Glucose , Glicemia , Insulina/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: Nowadays, hair dye products are widely used for aesthetic purposes, in which it generates chemical exposure to customers and, mainly, hairdressers. The aim of this systematic review was designed to elucidate the following question: are hair dye products able to induce DNA damage in hairdressers? METHODS: Studies were included in our analyses if they met the following criteria: (1) studies measuring genetic damage in vivo; (2) studies published in English; (3) studies that provided data clearly presented in scientific standards. RESULTS: Full manuscripts from 13 studies were carefully selected in this setting. Our results demonstrate that hair dye products may contain chemical agents able to induce DNA strand breaks or chromosome damage since the majority of studies demonstrated positive findings for genotoxicity. A total of 7 studies (out of 13) had strong or moderate rates in the quality assessment. The type of genotoxicity assay and sample selection criteria time influenced the outcome. CONCLUSION: In summary, our results reveal that hairdressers are occupationally exposed to genotoxic agents. Such findings are very important for protecting these professionals who are continuously exposed to chemicals for long periods.
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Tinturas para Cabelo , Humanos , Tinturas para Cabelo/toxicidade , Dano ao DNARESUMO
Collagen dressings have been widely used as effective treatments for chronic wounds acting as barrier, protecting the area from infections and participating in the healing process. Collagen from fish skin is biocompatible, presents low immunogenicity and is able of stimulating wound healing. In this scenario, skin of flounder fish (Paralichthys sp.) may constitute a promising source for collagen. Then, our hypothesis is that fish collagen is able of increasing cell proliferation, with no cytotoxicity. In this context, the aim of the present study was to investigate the physicochemical and morphological properties of collagen using scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), mass loss and pH. Moreover, the cytotoxicity and genotoxicity of collagen were studied using in vitro studies (cell viability, comet assay and micronucleus assay). Fish collagen showed no variation of pH and mass weight, with characteristic peaks of collagen in FTIR. Furthermore, all the extracts presented cell viability at least over 50% and no cytotoxicity was observed. Regarding genotoxicity data, the results showed that only the extract of 100% showed higher values in comparison with negative control group for CHO-K1 cell line as depicted by comet and micronucleus assays. Based on the results, it is suggested that fish collagen is biocompatible and present non-cytotoxicity in the in vitro studies, being considered a suitable material for tissue engineering proposals.
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Linguado , Cricetinae , Animais , Colágeno/farmacologia , Cicatrização , Pele/química , Peixes , Células CHORESUMO
The inorganic part of marine sponges, called Biosilica (BS), presents an osteogenic potential and the ability of consolidating fractures. Moreover, 3D printing technique is highly effective for manufacturing scaffolds for tissue engineering proposals. Thus, the aims of this study were to characterize the 3D rinted scaffolds, to evaluate the biological effects in vitro and to investigate the in vivo response using an experimental model of cranial defects in rats. The physicochemical characteristics of 3D printed BS scaffolds were analyzed by FTIR, EDS, calcium assay, evaluation of mass loss and pH measurement. For in vitro analysis, the MC3T3-E1 and L929 cells viability was evaluated. For the in vivo evaluation, histopathology, morphometrical and immunohistochemistry analyses were performed in a cranial defect in rats. After the incubation, the 3D printed BS scaffolds presented lower values in pH and mass loss over time. Furthermore, the calcium assay showed an increased Ca uptake. The FTIR analysis indicated the characteristic peaks for materials with silica and the EDS analysis demonstrated the main presence of silica. Moreover, 3D printed BS demonstrated an increase in MC3T3-E1 and L929 cell viability in all periods analyzed. In addition, the histological analysis demonstrated no inflammation in days 15 and 45 post-surgery, and regions of newly formed bone were also observed. The immunohistochemistry analysis demonstrated increased Runx-2 and OPG immunostaining. Those findings support that 3D printed BS scaffolds may improve the process of bone repair in a critical bone defect as a result of stimulation of the newly formed bone.
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Poríferos , Alicerces Teciduais , Animais , Ratos , Alicerces Teciduais/química , Cálcio , Poríferos/química , Dióxido de Silício , Impressão TridimensionalRESUMO
PURPOSE: The aim of this study was to evaluate if the micronucleus test using oral epithelial cells is a suitable biomarker for biomonitoring children exposed to X-ray. MATERIAL AND METHODS: A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to February 2022 that examined the relationship between exposure of children to radiographic examinations and micronucleus. RESULTS: A total of 17 full-text manuscripts were screened for eligibility. Only two studies found a difference in micronucleus labeling. On the other hand, all studies showed that X-ray was able to induce cellular death in oral mucosa cells. Following the parameters of the Effective Practices in Public Health Project (EPHPP), five manuscripts reached moderate and strong scores, and four studies were categorized as weak at final rating. In the meta-analysis, statistically significant difference was detected in micronucleated cells in children before and after radiographic examinations (SMD = 0.96, 95% CI, 0.07-1.84, p = .04), with τ2=1.09; χ2=53.37, and p < .001. CONCLUSION: Radiographic examinations in children can cause genotoxic and cytotoxic damage in the oral epithelium with a large effect size.
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Monitoramento Biológico , Células Epiteliais , Humanos , Criança , Testes para Micronúcleos/métodos , Raios X , Radiografia , Dano ao DNA , Mucosa BucalRESUMO
Wound dressings are one of the most used treatments for chronic wounds. Moreover, 3D printing has been emerging as a promising strategy for printing 3D printed wound constructs, being able of manufacturing multi layers, with a solid 3D structure. Although all these promising effects of 3D printed wound constructs, there is still few studies and limited understanding of the interaction of these dressings with skin tissue and their effect on the process of skin wound healing. In this context, the aim of this work was to perform a systematic review of the literature to examine the effects of 3D printed wound constructs on the process of skin wound healing in animal models. The articles were selected from three databases following Medical Subject Headings (MeSH) descriptors "3D printing," "skin," "wound," and "in vivo." After the selection, exclusion and inclusion criteria, nine articles were analyzed. This review confirms the significant benefits of using 3D printed wound constructs for skin repair and regeneration. All the used inks demonstrated the ability of mimicking the structure of skin tissue and promoting cell adhesion, proliferation, migration, and mobility. Furthermore, in vivo findings showed full wound closure in most of the studies, with well-organized dermal and epidermal layers.
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Pele , Engenharia Tecidual , Animais , Modelos Animais , Adesão Celular , Impressão TridimensionalRESUMO
Epidermal growth factor (EGF) and light-emitting diode (LED) are currently deployed as promissory treatments for skin repair; however, the mechanisms of their association are not yet evidenced. Thus, the present study aimed to evaluate the effects of combined treatment with EGF and red LED on the wound healing processes in rats. Adult Wistar rats were randomized in control group (CG) wounds without treatment; wounds submitted to EGF treatment (EGF); wounds submitted to LED treatment (LED); wounds submitted to EGF associated with LED treatments (EGF/LED). Treatments were performed immediately after the surgical procedure and each 24 h, totaling 8 sessions. Moreover, LED was applied before EGF treatment at a single point in the center of the wound. Morphological characteristics and the immunoexpression of COX-2, VEGF, and TGF-ß were measured. The results demonstrated that EGF/LED group presented a higher wound healing index. Additionally, all experimental groups presented similar findings in the histological evaluation, the degree of inflammation, and the area of dermis-like tissue. However, for EGF-treated animals (with or without LED), neoepithelial length was higher. Furthermore, all the treated groups decreased COX-2 and increased VEGF immunoexpression, and only EGF/LED group enhanced the TGF-ß protein expression when compared to the untreated group. This research shows that EGF and LED modulate inflammatory process and increase the vascularity. In addition, treatment of EGF associated with LED promoted a more evident positive effect for increasing TGF-ß expression and may be promising resources in the clinical treatment of cutaneous wounds.
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Fator de Crescimento Epidérmico , Fator A de Crescimento do Endotélio Vascular , Ratos , Animais , Fator de Crescimento Epidérmico/metabolismo , Ciclo-Oxigenase 2 , Ratos Wistar , Cicatrização , FototerapiaRESUMO
Abstract The aim of this systematic review was to evaluate published papers regarding the micronucleus assay in oral mucosal cells of patients undergoing orthodontic therapy (OT). A search of the scientific literature was made in the PubMed, Scopus, and Web of Science databases for all data published until November, 2021 using the combination of the following keywords: "fixed orthodontic therapy," "genetic damage", "DNA damage," "genotoxicity", "mutagenicity", "buccal cells", "oral mucosa cells," and "micronucleus assay". The systematic review was designed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Nine studies were retrieved. Some authors demonstrated that OT induces cytogenetic damage in oral mucosal cells. Out of the nine studies included, two were classified as strong, five as moderate, and two as weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed no relationship between mutagenicity in oral cells and OT in different months of treatment. At one month, the SMD = 0.65 and p = 0.08; after three months of OT, the SMD = 1.21 and p = 0.07; and after six months of OT, the SMD = 0.56 and p = 0.11. In the analyzed months of OT, I2 values were >75%, indicating high heterogeneity. In summary, this review was not able to demonstrate that OT induces genetic damage in oral cells. The study is important for the protection of patients undergoing fixed OT, given that mutagenesis participates in the multi-step process of carcinogenesis.
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To evaluate, through a systematic review, the assessment of genotoxicity of glass ionomer cements in vitro and in vivo. A systematic review was performed with the problem, intervention, control, and outcomes (PICOS) strategy, aiming to answer the following question: "Can glass ionomer cements induce genetic damage in vitro and in vivo?" A systematic search was performed in the following electronic databases: PubMed (including MedLine), Web of Science, and Scopus. The quality of included studies was assessed using the Effective Public Health Practice Project (EPHPP). After the authors performed the review of all articles, a total of 13 manuscripts met all the inclusion criteria in the systematic review. Following the parameters of the EPHPP, eight articles were classified as strong or moderate quality. The other ones (five studies) were weak. Taken together our results demonstrated that, six studies reported genotoxicity of the modified glass ionomer cements tested and two studies concluded that the effect of genotoxicity was time dependent.