The circadian rhythm regulates the physiology and behavior of living organisms in a time-dependent manner. Clock genes have distinct roles including the control over gene expression mediated by the transcriptional activators CLOCK and BMAL1, and the suppression of gene expression mediated by the transcriptional repressors PER1/2 and CRY1/2. The balance between gene expression and repression is key to the maintenance of tissue homeostasis that is disrupted in the event of an injury. In the skin, a compromised epithelial barrier triggers a cascade of events that culminate in the mobilization of epithelial cells and stem cells. Recruited epithelial cells migrate towards the wound and reestablish the protective epithelial layer of the skin. Although we have recently demonstrated the involvement of BMAL and the PI3K signaling in wound healing, the role of the circadian clock genes in tissue repair remains poorly understood. Here, we sought to understand the role of BMAL1 on skin healing in response to injury. We found that genetic depletion of BMAL1 resulted in delayed healing of the skin as compared to wild-type control mice. Furthermore, we found that loss of Bmal1 was associated with the accumulation of Reactive Oxygen Species Modulator 1 (ROMO1), a protein responsible for inducing the production of intracellular reactive oxygen species (ROS). The slow healing was associated with ROS and superoxide dismutase (SOD) production, and pharmacological inhibition of the oxidative stress signaling (ROS/SOD) led to cellular proliferation, upregulation of Sirtuin 1 (SIRT1), and rescued the skin healing phenotype of Bmal1−/− mice. Overall, our study points to BMAL1 as a key player in tissue regeneration and as a critical regulator of ROMO1 and oxidative stress in the skin.

Genotoxicity is the ability of an agent to produce damage on the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, to elucidate the putative mechanisms of genotoxicity induced by fluoride are important to measure the degree of risk involved to human populations. The purpose of this article is to provide a comprehensive review on genotoxicity induced by fluoride on the basis of its mechanisms of action. In the last 10 years, all published data showed some evidence related to genotoxicity, which is due to mitochondrial disruption, oxidative stress, and cell cycle disturbances. However, this is an area that still requires a lot of investigation since the published data are not sufficient for clarifying the genotoxicity induced by fluoride. Certainly, the new information will be added to those already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

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Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p < 0.05). Peripheral blood and liver cells presented genetic damage as depicted by single cell gel (comet) assay at 9 and 18 mg/kg doses (p < 0.05). Immunohistochemistry data revealed significant increase in 8-hydroxy-20-deoxyguanosine (8-OHdG) immunoexpression in hepatocytes of animals exposed to crack cocaine at 9 and 18 mg/kg (p < 0.05) when compared with negative controls. Taken together, our results demonstrate that crack cocaine is able to induce genomic damage in multiple organs of Wistar rats.

Background The aim of this study was to evaluate whether sleep deprivation (SD) induces inflammation, autophagy and myogenesis in the following masticatory muscles: masseter and temporal. Methods In this study, 18 animals were randomly distributed into three groups: control group (CTL, n = 6), SD for 96 hours (SD96, n = 6), and SD for 96 hours and more 96 hours of sleep recovery (SD96 + R, n = 6). Results In the histopathological analysis, SD 96 was able to induce inflammation in masseter and temporal. Nevertheless, the lack of inflammatory process was evidenced to the masseter in the group SD96 + R. Upregulation of TNF‐alpha production was detected in the SD96 group, while SD96 + R decreased TNF immunoexpression for both skeletal muscles evaluated. MyoD and myogenin increased in rats submitted to SD96. By contrast, the levels of MyoD decreased in the group SD96 + R. Myogenin pointed out high immunoexpression in SD96 + R groups. In temporal, pAkt decreased in animals submitted to SD96, but it increased in the group SD96 + R. The levels of LC3 protein increased in both skeletal muscles studied, and masseter decreased LC3 protein expression in the SD96 + R. Conclusion In summary, our results demonstrate that SD is able to induce inflammation, atrophy and myogenesis in rat masticatory muscles, being more intense in temporal when compared to masseter.

Dental X-rays are widely used in clinical practice, since the technique is an important approach for diagnosing diseases in dental and periodontal tissues. However, it is widely known that radiation is capable of causing damage to cellular systems, such as genotoxicity or cytotoxicity. Thus, the aim of this review was to present a critical analysis regarding the studies published on genotoxicity and cytotoxicity induced by dental X-rays in oral mucosa cells. Such studies have revealed that some oral cell types are more sensitive than others following exposure to dental X-rays. Certainly, this review will contribute to a better understanding of this matter as well as to highlighting perspectives for further studies. Ultimately, such data will promote better safety for both patients and dental professionals.

Taken together, our results indicate that street sweepers comprise an at-risk group as a result of increased mutagenicity found to buccal mucosa cells.