Maternal dietary fatty acid composition and content prior to and during pregnancy and lactation influences serum profile, liver phenotype and hepatic miRNA expression in young male and female offspring.

This study aimed to investigate whether modifying the pre-gestational lipid content could mitigate metabolic damage in offspring from dams exposed to a high-fat (HF) diet before conception and during pregnancy and lactation, with a focus on sex-specific outcomes. Specific effects of maternal normolipidic diets on offspring were also assessed. Female Wistar rats received control (C) or HF diets before conception. During pregnancy and lactation, females were distributed in five groups: C-C, HF-HF, HF-C, HF-saturated (HF-S) or HF-polyunsaturated n-3 group (HF-P). Saturated and PUFA n-3 diets were normolipidic. In 21-day-old offspring, corporal parameters, adiposity, serum metabolites, OGTT, liver phenotype, and miR-34a-5p hepatic expression were determined. Pre-gestational HF diet impaired glycemic response in females, independent of any change in body weight. Female and male offspring from dams continuously exposed to HF diet exhibited hyperglycemia, increased adiposity, and disrupted serum lipid profiles. Male offspring showed increased hepatic fat accumulation and miR-34a-5p expression. Shifting maternal dietary lipid content to normolipidic diets restored offspring's phenotype; however, decreased SIRT1, IRß and IRS1 expression in offspring from dams exposed to HF diet before conception suggested early indicators of glucose metabolism damage. Our findings indicated a pronounced metabolic impact on males. In conclusion, glucose tolerance impairment in females before conception disturbed intrauterine environment, influencing in offspring's phenotype. Modifying maternal dietary lipid content mitigated effects of pre-gestational HF diet exposure on young offspring. Nevertheless, decreased hepatic levels of critical insulin signaling proteins indicated that independently of the maternal diet, pre-existing HF diet-induced glucose intolerance before conception may adversely program the offspring's phenotype.

Cytogenotoxicity and inflammatory response in liver of rats exposed to different doses of cannabis nano emulsions.

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.

Comet assay as a suitable biomarker for in vivo oral carcinogenesis: a systematic review.

BACKGROUND AND OBJECTIVES: In order to detect genetic damage, different methods have been developed, such as micronuclei and comet assay. The comet assay presents some advantages when compared to the other aforementioned methods, including wide versatility, as any eukaryotic cell can be evaluated at an individual cellular level. In this context, the aim of this systematic review was designed to help further elucidate the following question: is the comet assay a suitable biomarker of in vivo oral carcinogenesis? MATERIAL AND METHODS: The present systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Full manuscripts from 18 studies were carefully selected in this setting. RESULTS: A total of 15 studies demonstrated positive findings for genotoxicity in peripheral blood or oral cells in patients with pre-malignant lesions or oral cancer. In the quality assessment of studies, 1 was classified as Strong, 5 were considered as Moderate, and 12 were classified as Weak. CONCLUSION: In summary, the comet assay can be a useful biomarker for oral carcinogenesis. However, further studies with more strict parameters are suggested (with less uncontrolled confounders) in order to increase findings reliability for diagnosis of oral potentially malignant lesions.

Degenerative changes induced by paradoxical sleep deprivation in rat sublingual glands.

PURPOSE: The aim of this study was to evaluate whether sleep deprivation can induce degenerative changes in rat sublingual glands. METHODS: For this purpose, a total of 24 males were distributed into three groups: control (n = 8), in which the animals were not subjected to any procedure; sleep deprivation (n = 8) in which the animals were submitted to sleep deprivation for 96 h; recovery (n = 8), in which the animals were subjected to paradoxical sleep deprivation for 96 consecutive hours followed by 96 h without intervention. Morphological changes in sublingual glands as well as the immunoexpressions of some proteins, such as Ki-67, p16, cleaved caspase-3 and BCL-2 were investigated in this setting. RESULTS: The results showed that paradoxical sleep deprivation induced tissue degeneration as a result of the presence of pyknosis, vacuoles and areas of salivary retention, in the experimental groups. Expression of cleaved caspase 3 and BCL-2 were increased in both sleep deprivation and recovery groups. The analysis of Ki-67 showed an increase in expression only in the recovery group, associated with a decrease in p16 levels. CONCLUSION: Sleep deprivation can induce a degenerative process in the parenchyma of sublingual gland by means of dysregulation of apoptosis associated with proliferative activity.

Modulation of non-coding RNAs by natural compounds as a potential therapeutical approach in oral cancer: A comprehensive review.

Oral cancer is a disease with high incidence and mortality worldwide, and its treatment still needs to be improved. The search for new therapies using natural products is strongly supported, given the wide chemical range of these compounds. In addition, phytochemicals can exert antitumor activities by several mechanisms of action, including the modulation of non-coding RNAs. Thus, in this review, we discussed the role of non-coding RNAs, including circular RNAs, microRNAs, and long non-coding RNAs, in oral cancer and presented their potential as treatment targets using natural products. Some natural products capable of being used to treat oral cancer have been suggested.

The influence of sex and reproductive cycle on cocaine-induced behavioral and neurobiological alterations: a review.

This systematic review (SR) was aimed at answering two questions: (1) how sex and ovarian hormones alter behavior associated with cocaine use; (2) which possible neurobiological mechanisms explain behavioral differences. Three different researchers conducted a search in PUBMED for all kinds of articles published between the years of 1991 to 2021 on the theme "reproductive cycle and cocaine", "estrous cycle and cocaine", "menstrual cycle and cocaine", "fluctuation of ovarian hormones and cocaine", "estrogen and cocaine" and "progesterone and cocaine". Sixty original studies were identified and subdivided into experimental rodent studies and clinical trials. Experimental studies were characterized by author/year, species/strain, sex/number, age/weight, dose/route/time of administration, hormonal assessment, or administration. Clinical trials were characterized by author/year, sex/number, age, exclusion criterion, dose/route of administration/time of cocaine, and hormonal assessment. Results gathered showed that rodent females develop increased consumption, seeking behavior, craving, relapse, locomotion, increases in stress and anxiety, among other behavioral alterations during peaks of estrogen. These observations are related to the direct effects played by ovarian hormones (in particularly estradiol), in dopamine, but also in serotonin neurons, and in brain regions such as the tegmental area, the nucleus accumbens, the hypothalamus, the amygdala and the prefrontal cortex. Increased sensitization to cocaine presented by high estradiol females was linked to the activation of a CBR1-mediated mechanism and GABA-A-dependent suppression of inhibitory synaptic activity of the prelimbic prefrontal cortex. Estradiol facilitation of cocaine-increased locomotion and self-administration was shown to require the release of glutamate and the activation of metabotropic glutamate receptors subtype 5. Clinical studies also tend to point to a stimulatory effect of estradiol on cocaine sensitization and a neuroprotective effect of progesterone. In conclusion, the results of the present review indicate a need for further preclinical and clinical trials and neurobiological studies to better understand the relationship between sex and ovarian hormones on cocaine sensitization.

Proinflammatory State in the Odontogenesis of Fetuses Exposed to Different Types of Fatty Acids during Pregnancy.

OBJECTIVES: The aim of the present study was to analyze the possible changes caused by the maternal ingestion of different types of fatty acids during pregnancy in the proinflammatory state in the odontogenesis of the fetuses. SUBJECT AND METHODS: Twenty-four jaws (n = 6 per group) of Wistar rats were collected on the 20th day of intrauterine life. Mothers were separated on the first day of pregnancy into 4 groups according to diet, as described below: control group (C) - diet with soy oil as a source of fat; saturated fatty acid group (S) - diet with lard in saturated fatty acids; trans-fatty acid group (T) - diet with vegetable fat, rich in trans-saturated fatty acids; and polyunsaturated fatty acid (PUFA) group - diet with fish oil, rich in PUFAs. RESULTS: Microscopic analysis showed no alterations in tissue development of the teeth between the groups with different lipid diets (T, S, and PUFA) when compared to the control group (C); immunohistochemical analysis for the expression of JAK2, STAT3, P-STAT3, SOCS3, and IL-6 showed no statistically significant difference (p > 0.05) compared to the control group. However, there were changes (p < 0.05) between the T group and the PUFA group in the expression of JAK2. CONCLUSION: Thus, lipid consumption in the maternal diet remains a topic to be explored in embryonic development, despite not causing morphological changes to the tooth germ of rats.

Is micronucleus assay in oral exfoliated cells a useful biomarker for biomonitoring populations exposed to pesticides? A systematic review with meta-analysis.

The systematic review (SR) with meta-analysis aimed to infer if micronucleus assay using oral mucosal cells a useful biomarker for biomonitoring populations continuously exposed to pesticides (EP). The SR has been made in accordance with the PRISMA-P guidelines. The PICOS strategy has focused to answer the following question: "Does exposure to pesticides cause genetic damage in oral cells?" The literature search was made in the following scientific databases: Web of Science, PubMed/Medline, and Scopus. The approach was defined as follows: standardized mean difference (SMD) and 95% confidence intervals (CI). The quality assessment of manuscripts was obtained by the EPHPP (Effective Public Health Practice Project). The GRADE tool was chosen for assessing the quality of evidence. A total of 108 articles were selected in this setting. After screening abstracts and titles, 23 manuscripts were evaluated for eligibility. After reviewing the studies, two were considered weak and 22 were classified as moderate or strong. The meta-analysis data pointed out statistically significant differences in volunteers exposed to EP (SMD = 1.23, 95% CI, 0.69 to 1.77, p < 0.001), with a Tau2 = 1.44; Chi2 = 566.38, and p < 0.001, so that the selected manuscripts were considered heterogeneous and the I2 of 97% indicated high heterogeneity. Taken together, this review was able to validate the micronucleus assay in oral exfoliated cells as a useful biomarker in individuals continuously exposed to EP because the studies categorized as moderate and strong have demonstrated positive response related to mutagenesis.

Cytotoxicity, Inflammatory Activity, and Angiogenesis Are Induced by Different Silicone Implants.

BACKGROUND/AIM: The aim of this study was to investigate cytotoxicity, inflammatory response, and angiogenesis induced by silicone gel breast implants with different textured surfaces in vitro and in vivo. MATERIALS AND METHODS: In the in vitro study, murine fibroblast cells (L929) were cultured for 1, 3, and 5 days with silicone membranes of three different textures: nanotextured, microtextured, and silicone foam. In the in vivo study, a total of 30 male rats (Rattus, norvegicus, albinos, Wistar) were distributed into three groups (10 animals per group), with 2 implants in each rat: nanotextured silicone gel breast implants group, microtextured silicone gel breast implants group, and silicone gel breast foam implants group. RESULTS: The Alamar Blue assay detected higher viability of cells cultured in the presence of nanotextured silicone surface for 1 and 3 days. The MTT assay showed higher cytotoxicity of silicone foam after 1 and 3 days of exposure. Nanotextured silicone breast implants induced a more prolonged inflammatory response, denoting a delay in the healing process and subsequent organization of the fibrous capsule as depicted by the collagen fiber types found. VEGF expression did not differ between experimental groups. CONCLUSION: Gel foam breast implants are more biocompatible when compared to micro- or nano-textured silicone breast implants.

Is micronucleus assay in oral exfoliated cells a suitable biomarker for predicting cancer risk in individuals with oral potentially malignant disorders? A systematic review with meta-analysis.

This systematic review (SR) with meta-analysis aimed to evaluate the scientific data related to cytogenetic damage in oral exfoliated cells of patients diagnosed with oral potentially malignant disorders (OPMDs). The SR was conducted according to the PRISMA-P guidelines. The PICOS (Participants, Intervention, Comparison, Outcome, and Study Design) strategy was used to answer the question: "Is micronucleus assay in oral exfoliated cells a suitable biomarker for predicting cancer risk in individuals with OPMDs?" The search strategy was performed in the following electronic databases: PubMed, Medline, Scopus and Web of Science. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CI). The quality of included studies was assessed using the EPHPP (Effective Public Health Practice Project). The GRADE tool was also utilized to assess the quality of evidence of the SR. A total of 110 potentially relevant studies were selected through the search strategy. After screening titles and abstracts, 20 full-text manuscripts were assessed for eligibility and three observational studies were included in the meta-analysis. After reviewing the 20 studies, 13 were considered weak. The meta-analysis data revealed a statistically significant difference in oral micronucleated cells by patients with OPMDs when compared to control (SMD=1.77, 95% CI, 0.36-3.18, p = 0.01), with a Tau2 = 1.97; Chi2 = 66.64, and p < 0.001. Patients with OPMDs had a positive response related to mutagenicity in oral cells compared to control patients. However, SR was not able to validate the micronucleus assay as a putative biomarker in individuals with oral potentially malignant disorders since the majority of studies were considered weak based on high risk of bias.

Is micronucleus assay in oral exfoliated cells a suitable tool for biomonitoring children exposed to environmental pollutants? A systematic review.

The aim of this review was to evaluate if micronucleus assay in oral exfoliated cells is a suitable tool for biomonitoring children exposed to environmental pollutants. Through the electronic databases PubMed/Medline, Scopus, and Web of Science, all published studies until April 2021 that examined the relationship between exposure to environmental pollutants and micronucleus frequency in oral cells were searched. All relevant articles using a combination of the following keywords-"children," "micronucleus," "oral cells," and "environmental pollution"-were considered. A total of 20 papers met the criteria for inclusion in the systematic review. The results regarding the cytogenetic damage induced by environmental pollutants are conflicting. Some authors have demonstrated that environmental pollution induces mutagenesis in oral cells while others did not. Following the parameters of the Project for Effective Public Health Practices (EPHPP) and after extensive reading of all the articles included, a total of 12 articles had moderate and strong scores and 8 had a classification considered weak. Taken together, this review was able to demonstrate the association between micronucleus frequency and exposure to environmental pollutants in oral exfoliated cells of children.

Does Panoramic X-ray Induce Cytogenetic Damage to Oral Cells? A Systematic Review With Meta-analysis.

AIM: The aim of this review was to evaluate the scientific literature regarding the cytogenetic damage in oral exfoliated cells of adult patients submitted to panoramic X-ray. MATERIALS AND METHODS: An extensive search of the literature was conducted on PubMed, Scopus and Web of Science databases for all studies published until April 2021 using combinations of the following keywords: "panoramic X-ray," "DNA damage," "genetic damage", "genotoxicity", "mutagenicity", cytotoxicity", "buccal cells", "oral mucosa", "tongue", "gingiva", "micronucleus assay", according to the PRISMA guidelines. All clinical studies in English language were included in the study. A total of 10 studies were identified. RESULTS: As expected, the results regarding the cytogenetic damage induced by panoramic X-ray are conflicting. Some authors have demonstrated that panoramic X-ray induces mutagenesis in oral cells, whereas others did not. After reviewing the 10 studies, two were classified as strong, four were considered moderate, and four were considered weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed a negative response related to mutagenicity in oral cells by panoramic X-ray. CONCLUSION: Taken together, this review failed to demonstrate the association between micronucleus frequency and panoramic X-ray.

Inhibition of Toll Like Signaling Pathway Is Associated With Genomic Instability in Rat Liver Exposed to Crack Cocaine.

BACKGROUND/AIM: The aim of the present study was to investigate the biological effects of subacute crack cocaine exposure in rat liver. MATERIAL AND METHODS: A total of 32 rats were distributed into four groups (n=8): Experimental group 1 (G1) and Experimental group 2 (G2): rats received 18 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day, group G2 remained 72 h without exposure after the experimental period (5 days)(abstinence); Experimental group 3 (G3): rats received 36 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day; Control Group (CTRL): rats received only the vehicle (DMSO) administered by the intraperitoneal (i.p) route for 5 days, once a day. RESULTS: All groups exposed to crack cocaine had an increase in the number of micronucleated hepatocytes and binucleated cells only in the highest tested dose (36 mg/kg). Karyolysis had an increase in the 18 mg/kg dose, in the abstinence group (G2), and 36 mg/kg group (G3); whereas pyknotic nuclei had an increase in the G2 group. The group exposed to 18 mg/kg of crack cocaine also showed high 8 OHdG expression. The p-NF-κB p65 protein decreased in the groups exposed to crack cocaine at doses of 18 and 36 mg/kg, as well as in the abstinence group. MyD88 was also found decreased in the group exposed to crack cocaine at 18 mg/kg. CONCLUSION: Crack cocaine inhibited toll like signaling pathway whilst being associated with genomic instability in rat liver cells.

Resveratrol effects in oral cancer cells: a comprehensive review.

Oral cancer is a very common tumor worldwide with high incidence and mortality. The treatment of oral cancer involves surgery, radio- and chemotherapy; however, high failure rates and toxicity are noticed. Thus, the search of new drugs aiming a more effective treatment is welcomed. Natural products present chemopreventive and anti-cancer effects. Resveratrol is a naturally occurring antioxidant that contains several health benefits, including anti-inflammatory and antiproliferative activities. This review discusses the different action mechanisms of resveratrol related in the in vitro and in vivo studies using models of oral cancer.

Carotenoids obtained from an ionic liquid-mediated process display anti-inflammatory response in the adipose tissue-liver axis.

Ionic liquids (ILs) have been proposed as more efficient and sustainable solvents to replace volatile organic solvents (VOSs). However, the drawbacks associated with their use are still limiting the regular application of bioactive compounds obtained from the processes they mediate as food ingredients. It is true that the number of ILs approved by the Food and Drug Administration for food applications is still low and mainly focused on the ones from the quaternary ammonium family. However, this trend is changing, judging from the evidence that industries are surpassing overgeneralization about ILs (on price and toxicity) and starting to consider the potential and performance of ILs as solvents. Despite the examples of industries applying ILs in their processes, the use of bioactive compounds obtained from IL-based processes as ingredients in food formulations is still a big challenge. The positive influence of carotenoids on diseases associated or originating from the inflammatory scenario including, among others, obesity, is not new. Moreover, it is also well known that the poorest population worldwide does not have the recommended intake of carotenoids, especially those pro-vitaminic A. In an attempt to help answer this issue, dietary supplements containing adequate doses of natural carotenoids are expected to be the solution, or at least, part of the solution for a healthier life, but also, to reduce hunger. Thus, complete studies evaluating the toxicological potential and the real viability of adding these bioactive compounds in food formulations proving (or not!) their safety to consumers and handlers are highly demanded. This work proposes to investigate the potential of carotenoids extracted from Bactris gasipaes feedstocks mediated by an ethanolic solution of an imidazolium-based IL. Thus, male Wistar rats were randomized in six different groups, supplemented or not by carotenoids extracted by IL or VOS, and fed by control- and/or high-fat-diets (HFD). The adipose tissue-liver axis was studied as a model to investigate the influence of the carotenoids on the levels of inflammation and oxidative stress markers. The main results showed that animals supplemented with carotenoids extracted with IL displayed improvements in serum parameters, besides lower metabolic efficiency, and antioxidant response on the liver, even when fed with HFD. However, animals supplemented with carotenoids extracted by VOS showed higher levels of pro-inflammatory markers and huge oxidative stress on the liver.

Dimethoate induces genotoxicity as a result of oxidative stress: in vivo and in vitro studies.

Dimethoate ([O,O-dimethyl S-(N-methylcarbamoylmethyl) phosphorodithioate]) is an organophosphate insecticide and acaricide widely used for agricultural purposes. Genotoxicity refers to the ability of a chemical agent interact directly to DNA or act indirectly leading to DNA damage by affecting spindle apparatus or enzymes involved in DNA replication, thereby causing mutations. Taking into consideration the importance of genotoxicity induced by dimethoate, the purpose of this manuscript was to provide a mini review regarding genotoxicity induced by dimethoate as a result of oxidative stress. The present study was conducted on studies available in MEDLINE, PUBMED, EMBASE, and Google scholar for all kind of articles (all publications published until May, 2020) using the following key words: dimethoate, omethoate, DNA damage, genetic damage, oxidative stress, genotoxicity, mutation, and mutagenicity. The results showed that many studies were published in the scientific literature; the approach was clearly demonstrated in multiple tissues and organs, but few papers were designed in humans. In summary, new studies within the field are important for better understanding the pathobiological events of genotoxicity on human cells, particularly to explain what cells and/or tissues are more sensitive to genotoxic insult induced by dimethoate.

Genotoxicity, oxidative stress, and inflammatory response induced by crack-cocaine: relevance to carcinogenesis.

Crack-cocaine is a cocaine by-product widely consumed by general population in developing countries. The drug is low cost and is associated with more intense effects when compared to other illicit drugs. Genotoxicity, oxidative stress, and inflammatory response are considered crucial events in carcinogenesis, since they actively participate in the multistep process. The purpose of this paper was to provide a mini review regarding the relationship between carcinogenesis and genotoxicity, oxidative stress, and inflammation induced by crack-cocaine. The present study was conducted on search of the scientific literature from the published studies available in PubMed, MEDLINE, Scopus, and Google Scholar for all kind of articles (all publications to November 2020) using the following key words: crack-cocaine, DNA damage, genotoxicity, cellular death, cytotoxicity, mutation, oxidative stress, inflammation, and mutagenicity. The results showed that published papers available were almost all in vivo test system being conducted in humans or rodents. Crack-cocaine was able to induce genotoxicity and oxidative stress in mammalian cells. However, the role of inflammatory response after exposure to crack-cocaine was not conclusive so far. In summary, this study is consistent with the notion that crack-cocaine is a chemical carcinogen as a result of genotoxicity and oxidative stress induced in mammalian and non-mammalian cells.