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Obesity and overweight are multifactorial diseases affecting more than one-third of the world's population. Physical inactivity contributes to a positive energy balance and the onset of obesity. Exercise combined with a balanced diet is an effective non-pharmacological strategy to improve obesity-related disorders. Gallic acid (GA), is a natural endogenous polyphenol found in a variety of fruits, vegetables, and wines, with beneficial effects on energetic homeostasis. The present study aims to investigate the effects of exercise training on obese mice supplemented with GA. Animal experimentation was performed with male Swiss mice divided into five groups: ST (standard control), HFD (obese control), HFD + GA (GA supplement), HFD + Trained (training), and HFD + GA + Trained (GA and training). The groups are treated for eight weeks with 200 mg/kg/body weight of the feed compound and, if applicable, physical training. The main findings of the present study show that GA supplementation improves liver fat, body weight, adiposity, and plasma insulin levels. In addition, animals treated with the GA and a physical training program demonstrate reduced levels of anxiety. Gene expression analyses show that Sesn2 is activated via PGC-1α independent of the GATOR2 protein, which is activated by GA in the context of physical activity. These data are corroborated by molecular docking analysis, demonstrating the interaction of GA with GATOR2. The present study contributes to understanding the metabolic effects of GA and physical training and demonstrates a new hepatic mechanism of action via Sestrin 2 and PGC-1α., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells., Methods: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies., Results: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53., Conclusions: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Malnutrition is a complicated illness that affects people worldwide and is linked to higher death rates, a heightened vulnerability to infections, and delayed cognitive development. Experimental models have been constructed to comprehend the mechanisms associated with hunger. In this regard, the current study used two different types of food aiming to validate a murine model of malnutrition based on dietary restriction. The study was conducted with fifty-six Swiss male mice (eight-week-old) divided into eight groups (n=7 each) and fed the following experimental diets (10 weeks): Standard Diet (ST) ad libitum; ST 20% dietary restriction; ST 40% dietary restriction; ST 60% dietary restriction; AIN93-M diet ad libitum; AIN93-M 20% dietary restriction; AIN93-M 40% dietary restriction; AIN93-M 60% dietary restriction. Body, biochemical, and histological parameters were measured, and the restriction effects on genes related to oxidative stress (GPX1 and GPX4) in epididymal adipose tissue were evaluated. The results obtained showed that 20%, 40%, and 60% of dietary restrictions were able to reduce body weight when compared to controls, highlighting the accentuated weight loss in animals with 60% restrictions, especially those fed with AIN-93 M, which showed physical changes such as whitish skin and dull coat, voracious eating, and hunched posture. The present animal model also showed biochemical changes with hypoalbuminemia, as well as histological epididymal adipose tissue modulation. The presence of increased oxidative stress was observed when evaluating the GPX4 gene. Given the results, 60% food restriction using the AIN93-M diet was the best protocol for inducing malnutrition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Edible insects are recognized as promising food sources due to their nutritional composition. Some species, such as Gryllus assimilis, contain proteins, lipids, and carbohydrates of high biological value, which regulate several metabolic functions, including the Renin-Angiotensin System (RAS). In this context, the present study aimed to assess the effects of dietary supplementation with whole Gryllus assimilis powder on the metabolism of malnourished mice. Thirty-two male Swiss mice were used and divided into four treatment groups. The groups were identified as (AIN93-M); AIN93-M + Gryllus assimilis diet (AIN93-M + GA); AIN93-M + Renutrition diet (AIN93-M + REN) and AIN93-M + Renutrition diet + Gryllus assimilis (AIN93-M + REN + GA). The results showed that whole Gryllus assimilis powder inclusion promotes recovery from protein-energy malnutrition, reduces adiposity, and improves glucose tolerance and insulin sensitivity. It also reduces total cholesterol, triglycerides, VLDL, and adipocyte area. We also observed a significant increase in the expression of RAS-related genes, such as ACE2 and MasR, followed by a reduction in Angiotensinogen and ACE. The main findings of the present study suggest the use of black cricket as a viable strategy for the prevention and treatment of protein-energy malnutrition, as well as the reduction of adiposity, and improvement of lipid and glycemic parameters, with antihypertensive potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To identify predictors of sarcopenia (demographical, anthropometric measurements, tumor-related clinical characteristics, performance status, and serum C-reactive protein (CRP) and albumin levels in individuals with head and neck squamous cell carcinoma (HNSCC)., Material and Methods: This cross-sectional study selected diagnosed with HNSCC (n = 125). Sarcopenia was defined as low muscle strength and low physical performance. Association between sarcopenia and anthropometric assessments (weight, height, body mass index, triceps skinfold, mid-upper arm circumference [MUAC], mid-upper arm muscle circumference, mid-upper arm fat area [UFA], mid-upper arm bone free muscle area, calf circumference, and appendicular skeletal muscle mass and index), tumor clinical characteristics (anatomical site, tumor size, and cervical metastasis), performance status scale (Eastern Cooperative Oncology Group Performance Status [ECOG-PS]), and CRP and albumin levels was analyzed using binary logistic regression models., Results: The diagnosis of sarcopenia was identified in 28 (22.4%) individuals with HNSCC. Being an older adult increases the odds of association with sarcopenia in individuals with HNSCC (odds ratio [OR] = 1.05). Increments in MUAC measurement reduce the odds of association with sarcopenia (OR = 0.69), while the increase in the UFA measurement increases the odds of association with sarcopenia (OR = 1.33). Poor ECOG-PS scores increase the odds of association with sarcopenia in individuals with HNSCC (OR = 5.54)., Conclusion: Early identification of easy-to-perform, cost-effective predictors of sarcopenia tends to favor the implementation of personalized therapeutic and supportive interventions in individuals with HNSCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed in vitro assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, in vivo studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs., (© The Author(s).)

Objective: Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. The current study aimed to identify potential biomarkers associated with OSCC survival., Materials and Methods: Differentially expressed genes (DEGs) in atypical OSCC cases were identified using two public datasets: The Cancer Genome Atlas and the Gene Expression Omnibus database. Receiver operating characteristic (ROC) analysis was performed to identify the cutoff, and the candidate DEGs related to survival. Kaplan-Meier and Cox regression analysis using the categorized genes were employed to identify genes that impact the overall survival in OSCC., Results: A total of 263 OSCC samples and 105 healthy tissues were used to identify 295 upregulated and 131 downregulated genes expressed only in non-smokers. ROC analyses identified 25 candidate genes associated with death. Survival analyses demonstrated that the following DEGs, namely CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5, are potential OSCC prognostic factors., Conclusion: We found that CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5 are associated with a low survival rate in OSCC. However, further studies are needed to validate our findings and facilitate the development of these factors as potential biomarkers for OSCC survival., (© 2022 Wiley Periodicals LLC.)

Background: Diet macronutrient heterogeneity hinders animal studies' data extrapolation from metabolic disorders to human diseases., Objective: The present study aimed to evaluate different fat-diet compositions' effect on inducing lipid/glucose metabolism alterations in mice., Methods: Swiss male mice were fed for 12 weeks with five different diets: Standard Diet (ST), American Institute of Nutrition 93 for growth (AIN93G) high-butter/high-sugar (HBHS), high-lard/high-sugar (HLHS), and high-oil/high-sugar diet (soybean oil) (HOHS). Several parameters, such as serum biochemistry, histology, and liver mRNA expression, were accessed., Results: The main findings revealed that the HLHS diet dramatically altered liver metabolism inducing hepatic steatosis and increased total cholesterol, triglycerides, VLDL, increasing liver CCAAT/enhancer binding protein (CEBP-α), Acetyl-CoA carboxylase (ACC) and Catalase (CAT) mRNA expression. Moreover, the HLHS diet increased glucose intolerance and reduced insulin sensitivity., Conclusions: High-fat/high-sugar diets are efficient to induce obesity and metabolic syndrome-associated alterations, and diets enriched with lard and sugar showed more effective results.

Differences in the features of aggressiveness of non-melanoma skin cancer (NMSC) subtypes, between basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are relevant characteristics. Comparing the characteristics between NMSC subtypes might help identify molecules associated with cancer metastasis and invasion. Considering these facts, the current study aimed to identify a molecular target for inhibiting skin cancer metastasis and invasion. Proteomic analysis suggested that heat shock protein 90 kDa, alpha, class B member 1 (HSP90AB1), pentaxin (PTX3), caspase-14 (CASP14), S100, actin-1, and profilin were the primary targets related to metastasis and invasion. However, after a differential expression comparison between BCC and SCC, HSP90AB1 was identified as the best target to repress metastasis and invasion. Based on molecular docking results, gallic acid (GA) was selected to inhibit HSP90AB1. A specific Hsp90ab1 siRNA targeting was designed and compared to GA. Interestingly, GA was more efficient in silencing HSP90AB1 than siRNAhsp90ab1. Hence, our data suggest that HSP90AB1 is a crucial biomarker for identifying invasion and metastasis and that its inhibition may be a viable strategy for treating skin cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study investigated the antineoplastic effects of crotoxin isolated from snake venom of the South American Crotalus durissus terrificus in oral cancer cell lines and in an animal model of chemically induced oral cancer. We analyzed cell viability and death, clonogenic formation, DNA fragmentation, migration assay, and gene expression of MMP2, MMP9, COL1A1, and CASP3. In the animal model, after induction of oral cancer by 4-nitroquinoline-1-oxide carcinogen, mice were treated with crotoxin to investigate its effects on tumor development in tongue and oral mucosa. Crotoxin inhibited cell proliferation, viability, colony formation, and migration, favoring cell death. Furthermore, crotoxin increased caspase-3 expression, decreased Ki-67 protein and mRNA expression of MMP2, MMP9, and COL1A1. Mice treated with crotoxin at 10 μg/kg did not alter biochemical parameters total cholesterol, very-low-density lipoprotein, high-density lipoprotein, liver transaminases, glycemia, creatinine, and urea. Crotoxin treatment significantly reduced the frequency of oral squamous cell carcinoma lesions by 50%. Thus, this study highlights crotoxin as a promising chemotherapeutic substance, considering its effects on controlling the neoplastic cell population, reducing cell migration, and inhibiting tumor development. Clinical studies are necessary to understand better the impact of crotoxin as a potential adjuvant therapeutic agent for oral cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Radiation therapy for head and neck squamous cell carcinoma (HNSCC) is associated with several complications. Although photobiomodulation (PBM) has radioprotective effects in normal tissue, it could also enhance the growth of neoplastic cells. Thus, the present study aimed to investigate the cellular response of oral squamous cell carcinoma with pre-exposure to low-level phototherapy before radiotherapy. SCC9, Cal-27, A431, and HaCaT cell lines were subjected to low-level light therapy and radiotherapy. The cells were treated with a single energy density (300 J/cm 2 ) of a light-emitting diode (660 nm) prior to ionizing radiation at different doses (0, 2, 4, and 6 Gy). After 24 h, wound scratch, proliferation, clonogenic cell survival, cell death, and reactive oxygen species (ROS) analyses were performed to evaluate cell response. The cell lines pre-exposed to PBM at the analyzed dosage were radiosensitive. The treatment significantly reduced cell proliferation and clonogenic cell survival. Migration and cell death assays also revealed positive results, with the treatment group showing lower rate of migration and higher cell death than did the control group. Moreover, PBM effectively increased the intracellular levels of ROS. PBM at 300 J/cm 2 is a promising radiosensitizing modality to reduce the radiation dose and avoid the intolerable side effects of radiotherapy for HNSCC, thus increasing the probability of successful treatment. However, further studies are needed to support and confirm the results., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

This study aimed to verify the action of bioactive compounds from Brazilian plants on the leader genes involved in the SARS-CoV-2 pathway. The main human genes involved were identified in GeneCards and UNIPROT platforms, and an interaction network between leader genes was established in the STRING database. To design chemo-biology interactome networks and elucidate the interplay between genes related to the disease and bioactive plant compounds, the metasearch engine STITCH 3.1 was used. The analysis revealed that SMAD3 and CASP3 genes are leader genes, suggesting that the mechanism of action of the virus on host cells is associated with the molecular effects of these genes. Furthermore, the bioactive plant compounds, such as ascorbate, benzoquinone, ellagic acid, and resveratrol was identified as a promising adjuvant for the treatment inhibiting CASP3-mediated apoptosis. Bioactive plant compounds were verified as the main pathways enriched with KEGG and related to viral infection, assessments/immune/infections, and cell proliferation, which are potentially used for respiratory viral infections. The best-ranked molecule docked in the CASP3 binding site was rutin, while the SMAD3 binding site was resveratrol. In conclusion, this work identified several bioactive compounds from Brazilian plants showing potential antiviral functions that can directly or indirectly inhibit the new coronavirus.

Purpose This study aimed to compare the efficacy of Antimicrobial Photodynamic Therapy (aPDT) with 300 µmol/L of methylene blue and 8 µmol/L of curcumin on oral candidiasis patients with HNSCC undergoing treatment. Methods A two-arm, single-blind clinical trial was performed. Following verification for eligibility (n = 447), 108 patients were included in the study. The study consisted of a group that received aPDT with methylene blue (n = 57) and another that received aPDT with curcumin (n = 51). The patients rinsed their mouths with an aqueous solution of 300 µmol/L of methylene blue and 8 µmol/L of curcumin in four sessions, and then the lesion was scraped for the subsequent RT-qPCR. The primary outcome was that no cure was presented for oral candidiasis after treatment. The secondary result was reducing the number of sites affected by oral candidiasis. Results There was no difference in treatment failure evaluated by the necessity of drug prescription or Candida sp DNA quantification. However, clinically the methylene blue protocol reduced the number of infected anatomical sites compared to the curcumin protocol. Conclusion Methylene blue aPDT reduced the number of infected anatomical sites compared to curcumin., Competing Interests: Declaration of Competing Interest The authors deny any conflicts of interest related to this study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We analyzed the distribution characteristics of the scientific production of Brazilian dentistry researchers of the Brazilian National Council for Scientific and Technological Development. The Lattes curriculum data of 211 researchers from Oral Pathology, Oral Surgery, and Oral Medicine fields were included (2018-2020). Over their academic career, 39 researchers published 7,555 papers (average, 175 articles/researcher); 3,876/7,555 papers were indexed in the Web of Science. During 2018-2020, 1,440/7,555 (19%) papers were published. Brazilian dental researchers contribute significantly to international research by participating in scientific journals' editorial boards, evaluating research promotion agencies, training researchers, and contributing to scientific and technological development.

The aim of this study is to investigate the antineoplastic potential of photodynamic therapy (PDT) mediated by an aluminum-phthalocyanine chloride nanoemulsion (AlPc-NE), against an oral squamous cell carcinoma (OSCC) cell line in vitro. Both OSCC (SCC9) and A431 cell lines were studied in vitro. Four study groups were used: Group 1 (phosphate-buffered saline [PBS]), Group 2 (PBS + 28.3 J/cm 2 irradiation), Group 3 (AlPc-NE alone), and Group 4 (AlPc-NE + 28.3 J/cm 2 irradiation). To test the effect of PDT with AlPc-NE, cell viability, migration, and cell death assays were performed. Moreover, the expressions of Ki-67 and TP53 were evaluated using immunoassays. The results showed that PDT mediated by all AlPc-NE concentrations evaluated (i.e., 0.7, 0.35, and 0.17 nM AlPc) significantly reduced the viability of SCC9 cells. Migration and cell death assays also revealed that PDT with AlPc-NE significantly reduced the rate of migration and increased cell death compared to the control groups. In addition, it was found that PDT with AlPc-NE reduced Ki-67 and mutated TP53 immunoexpression. PDT with AlPc-NE is effective in reducing the viability and migration of SCC9. Moreover, PDT with AlPc-NE nanoemulsions reduces the cell proliferation and expression of mutant TP53., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Head and neck squamous cell carcinoma (HNSC) etiopathogenesis remains unclear, and the biological changes with the activation of heat shock proteins (HSPs) and prion protein (PRNP) promoted by hypoxia in HNSC are undetermined. This study investigates hypoxia's effect in lymph node metastasis by PRNP expression changes and its main partners., Methods: The study combined a theoretical/cell culture study with a case-control study. First, bioinformatics and cell culture were performed. A case-control study was performed in a second step by comparing HNSC patients with and without lymph node metastasis., Analyses: The Cancer Genome Atlas (TCGA) data source validates the theory in the global population study., Results: Bioinformatics analysis suggests that hypoxia-inducible factor-1α (HIF1A) is associated with HSPA4, HSP90AA1 and PRNP expression. TCGA data validate the hypothesis that higher HSP90AA1, HSPA4 and PRNP are related to metastases and low survival. Herein, the cell study demonstrated that muted PRNP did not respond to hypoxia., Discussion: Our results collectively provide the first evidence that PRNP promotes HNSC lymph node metastasis progression through the upregulation of HSPA4, HSP90AA1 and HIF1A. Our findings may provide a molecular basis for the promoting Role of PRNP in HNSC progression., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The purpose of the present study was to investigate the effect of acupuncture on xerostomia in irradiated patients with head and neck squamous cell carcinoma (HNSCC)., Study Design: A preventive, 2-arm, parallel, single-blind trial was performed. Patients with HNSCC (N = 296) were checked for eligibility, and 107 patients were enrolled in the study. The study comprised 1 group that did not receive the intervention (n = 55) and the interventional group that received traditional and auricular acupuncture (n = 52). The primary outcome was the reduction of the patients' xerostomia after treatment. In addition, the secondary outcome was the reduction of anxiety., Results: The current acupuncture protocol reduced the xerostomia score and increased saliva volume and density without changing salivary pH. Additionally, acupuncture decreased the Beck Anxiety Inventory (BAI) score after radiation therapy., Conclusion: Combining traditional and auricular acupuncture reduced xerostomia and increased saliva volume without changing the saliva's pH in irradiated patients with HNSCC. Additionally, the combination of traditional and auricular acupuncture reduced BAI scores., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction  Intra and postoperative bleeding are the most frequent and feared complications in adenotonsillectomy (AT). Tranexamic acid (TXA), which is known for its antifibrinolytic effects, has a proven benefit in reducing bleeding in hemorrhagic trauma and cardiac surgery; however, the effectiveness and timing of its application in AT have not yet been established. Objectives  We aimed to evaluate the efficacy of TXA in controlling bleeding during and after AT and assess its possible adverse effects in children. Methods  The present randomized, controlled, double-blind clinical trial included 63 children aged 2 to 12 years. They were randomly assigned to receive either intravenous TXA (10 mg/kg) or placebo 10 minutes before surgery. The volume of intraoperative bleeding, presence of postoperative bleeding, and adverse effects during and 8 hours after the surgery were assessed. Results  No difference in bleeding volume was noted between the 2 groups (mean, 122.7 ml in the TXA group versus 115.5 ml in the placebo group, p  = 0.36). No intraoperative or postoperative adverse effects were noted because of TXA use. Furthermore, no primary or secondary postoperative bleeding was observed in any of the participants. Conclusion  In our pediatric sample, TXA (10 mg/kg) administration before AT was safely used, without any adverse effects. It did not reduce the bleeding volume in children during this type of surgery. Future studies should assess the use of higher doses of TXA and its administration at other time points before or during surgery., Competing Interests: Conflict of Interests The authors have no conflict of interests to be declared, (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Obesity is a chronic disease caused multiple associated factors that results in excessive body fat accumulation. The Renin-Angiotensin System (RAS) unbalance is now recognized as a key factor on regulating body energy and metabolism., Aim: The aim of the present study was to evaluate the Enalapril (ACE inhibitor) effects on the metabolic function and hepatic steatosis of obese mice evaluating Angiotensin Converting Enzymes (ACEs) expression., Methods: The experiment was performed using 32 male Swiss mice (8 weeks old) equally and randomly divided into 4 groups (n = 8): standard diet (ST), standard diet plus Enalapril (ST + ENAL), hyperlipidic diet (HF) and hyperlipidic diet plus Enalapril (HF + ENAL). Weekly measurements of animal weight and feed consumption were performed. At the end of treatment period a glucose tolerance test (GTT) and insulin sensitivity test (IST) were performed. Ultrasonography was used to evaluate hepatic and epididymal fat pad. Liver samples were submitted to HE histology and gene expression analyses were performed using Real-Time PCR., Results: The main results showed a decrease in body weight after treatment with Enalapril, as well as a reduced size of epididymal fat pad (EFP). Hepatic echogenicity and steatosis measurement were lower in the obese groups treated with Enalapril also modulating ACE2/ACE expressions., Conclusions: Enalapril use improved metabolism reducing hepatic steatosis, decreasing ACE expression and increasing ACE2 expression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Brazilian flora is rich in plants with medicinal properties, which though popular, has contributed to the development of a range of phytotherapic products that use plants to treat and cure diseases. However, studies that use Brazilian plants in the treatment of metabolic disorders are still scarce in the literature., Objective: The aim of this study was to analyze the effect of hepatotoxicity Lafoensia pacari on the metabolism of mice with obesity induced by a high-fat diet and to verify the phytochemical difference between the Lafoensia pacari bark of the trunk, leaves, and branches., Methods: The plant material was collected from April to May in the municipality of Bonito de Minas, MG, Brazil. Qualitative tests for the presence of secondary metabolite classes were performed for leaves, branches and bark of the trunk. Through histological analysis, we evaluated hepatocytes and cell lesions in the liver., Results: The comparative phytochemical analysis of the plant did not reveal alterations between the different plant parts. The phytochemical test showed that is preferable to use the leaves to make the extract to be applied, aiming to reduce the plant aggression. After treatment, greater changes were observed in the animals that received the high-fat diet and the hydroethanolic extract; the levels of AST, ALT, albumin and creatinine that were increased, thus demonstrating a possible toxicity. There were no significant differences in body weight. In the histological analysis, the animals without plant treatment displayed decreased liver weight and reduction in the inflammatory infiltrate., Conclusion: We conclude that Lafoensia pacari should be better evaluated for oral consumption and may cause liver damage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases., Objective: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells., Methods: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards., Results: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation., Conclusion: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer patients present a higher risk of experiencing anxiety disorders (AD). However, it is not clear if AD might be associated with cancer development. Thus, our study aimed to evaluate if AD might be related to head and neck squamous cell carcinoma (HNSCC) development. The combination of an applied animal basic study and a retrospective diagnostic case and control study in patients was performed. As a result, we obtained that stress reduced the locomotor activity of the animals in the group stress and stress + 4NqO (p < 0.0001). The stress showed no influence on the progression of neoplasia in mice. In the same way, the case group did not present differences in anxiety scores in comparison to control. Moreover, no association between HNSCC staging and anxiety scores was observed. In conclusion, our in vivo findings in humans and animals have shown that there is no relationship between AD and oral squamous cell carcinoma., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 The Authors.)

Oral Mucositis (OM) is a common adverse effect of head and neck squamous cell carcinoma (HNSCC) treatment. The purpose of this study was to investigate the significance of early changes in tissue electrical parameters (TEPs) in predicting the development of OM in HNSCC patients receiving radiation therapy (RT). The current study combined two study designs. The first was a case-control study. The control group comprised of RT patients who did not receive head and neck RT, and patients with HNSCC who received RT comprised the case group. In the second part of the study, the case group was included in a parallel cohort. A total of 320 patients were assessed for eligibility, and 135 patients were enrolled. Double blinding was performed, and neither the patients nor the care providers knew the measured parameters. The primary outcome was the detection of between-group changes in local TEPs over the follow-up period. The secondary outcome was the appearance of OM grades II, III, or IV and the predictive value of local TEPs in determining the incidence of OM after RT. The variables, impedance module, resistance, reactance, phase angle, and capacitance, were analyzed by the receiver operator curves (ROC). The case and control groups did not differ in demographic and clinical characteristics. Radiation therapy increased the local impedance module, resistance, reactance, and phase angle and reduced the local tissue capacitance in both groups. Evaluation of TEPs in the first week of RT correlated with the development of OM lesions during cancer therapy. ROC analysis showed that local impedance module and resistance presented higher specificity than did other parameters in predicting OM. In conclusion, local tissue electrical parameters measured at the first RT week can be useful tools to predict oral mucositis.

Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.

Objective: Malignant salivary gland tumors (MSGTs) present different phenotypic characteristics and various clinical outcomes, which proved to be a diagnostic challenge. Considering the heterogeneity of MSGT, this study aims to identify molecule related to the nature of MSGT., Methods: For screening, proteomic analysis comparing MSGT with pleomorphic adenoma (PA) and salivary gland was performed. The MSGT-associated protein which presented in the higher number in the Gene Expression Omnibus (GEO) database was selected. To validate the data, immunohistochemistry (IHC) was performed in 14 patients with PA, 22 patients with MSGT, and 14 controls., Results: 16 proteins were associated with MSGT. ANXA2 was the primary protein, according to GEO database analyses. ANXA2 was most expressed in the cell membrane. However, some ANXA2 staining was also observed in the cytoplasm and nucleus. ANXA2 was highly expressed in MSGT in comparison with control. Also, ANXA2 has a higher expression in adenocarcinoma not otherwise specified (ANOS) and myoepithelial carcinoma (MC) in comparison with PA., Conclusion: In conclusion, this study demonstrated that MSGT presented higher levels of ANXA2 in comparison with normal salivary glands. Also, ANXA2 might be interesting as a molecular marker of ANOS and MS., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There is significant controversy in the literature regarding the relationship between hypoxia and salivary gland neoplasms (SGNs)., Objective: The current study aims to investigate levels of hypoxia markers in both benign and malignant salivary neoplasms., Patients and Methods: The current study sample is comprised of a total of 62 samples. HIF-1α expression was evaluated by immunohistochemistry. Additionally, HIF-1α mRNA and miR-210 levels were assessed using qRT-PCR., Results: No differences in HIF-1α expression were observed among the control group, benign and malignant SGNs. Similarly, HIF-1α mRNA levels were similar between benign and malignant SGNs. Also, there was no difference in miR-210 expression between case and control groups., Conclusion: The angiogenic markers, miR-210 and HIF-1α, do not appear to distinguish malignancy in salivary glands., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Because the impact of conditioned fear stress on apical bone resorption is unknown, the aim of the current studywas to use a rat model to evaluate the impact of conditioned fear stress on the bone resorption of inflammatory apical periodontitis lesions., Methods: Twenty-five animals were divided into two groups. They underwent a surgical procedure in the first left lower molar tooth to expose the dental pulp and induce inflammatory apical periodontitis lesions through the retention of contamination (bacterial infection) during a 56-day period. The animals in the case group were stressed daily by using electrical stimuli (1.10 mA), whereas the animals in the control group were absent from the stressful stimuli (shocks). The open field test was performed to validate the stress methodology. The jaws were removed and collected for histological and radiographic analyses., Results: Stressed animals presented increased levels of bone loss and inflammatory cells in the root apex in comparison with the control group (P = 0.0001). However, no radiographic differences were observed between the groups (P > 0.05)., Conclusions: Our results demonstrated that conditioned fear stress could modify a periapical lesion by increasing the size of bone loss there. Conditioned fear stress also increased the total number of inflammatory cells compared with the control group. Studies evaluating the impact of conditioned fear stress on human periapical inflammatory lesions should be encouraged., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Leptin, an important hormone controlling energy homeostasis, has been linked to the pathogenesis of oral squamous cell carcinoma (OSCC). Evidence indicates that head and neck cancer patients undergoing radiotherapy show decreased leptin levels after radiotherapy treatment. Thus, we investigated, through phenotypic and molecular analyses, whether leptin can compromise the therapeutic effect of ionizing radiation and neoplastic behavior of OSCC cells., Methods: The human OSCC-derived cell lines SCC9 and SCC4 were treated with human recombinant leptin and exposed to 6 Gy of irradiation. We performed the in vitro assays of cell migration, death, proliferation, and colony-forming ability. The reactive oxygen species (ROS) levels and proteome analysis by mass spectrometry were also conducted., Results: Leptin was able to increase cell proliferation, migration, and colony-forming ability, despite the suppressive effect induced by irradiation. Furthermore, the leptin promoted a significant reduction of ROS intracellular accumulation, and increased expression of the cancer-related proteins, as ACTC1, KRT6A, and EEF2 in irradiated OSCC cells., Conclusions: Our findings suggest that leptin impairs responsivity of OSCC cells to the ionizing radiation, reducing the suppressive effects of irradiation on the neoplastic phenotype, and increasing protein expression critical to carcinogenesis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the most common adverse effects of OSCC treatment. Currently, there is no consensus for OM treatment. The purpose of the current study was to test the combination of red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture of human fibroblast was performed to identify LLLT dose. After laboratory tests, a two-arm parallel, single-blind, controlled study was conducted. The two arms were group 1, both 660- and 808-nm wavelengths (300 J/cm 2 , 9 J of total energy, 100 mW, spot size 3 mm 2 ), and group 2, only 660-nm wavelength (300 J/cm 2 , 9 J of total energy, 100 mW, spot size 3 mm 2 ). Both treatments were performed twice a week. Group 1 presented a reduction of mucositis grade in comparison to group 2. Group 1 also presented reduction of analgesics prescription. But no significant differences between groups 1 and 2 were observed according to the pain scale. In conclusion, the current study demonstrated that a combination of red and infrared at a higher dose (300 J/cm 2 ) reduced both oral mucositis grade and analgesics prescription. The effects of the combination of RT and LLLT are unclear and need more studies.

Chikungunya virus causes fever and severe polyarthritis or arthralgia and is associated with neurologic manifestations that are sometimes challenging to diagnose. We demonstrate intrathecal synthesis of chikungunya antibodies in a patient with a history of acute infection complicated by encephalitis. The specificity of the intracerebral immune response supports early chikungunya-associated encephalitis diagnosis.

Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Introduction: The Renin-Angiotensin System (RAS) has emerged as being related to vascular disease. Recently the RAS has been associated with obesity, diabetes, and even cancer., Objective: This review and Bioinformatics analyses focuses on the investigation of Angiotensinconverting enzymes (ACE and ACE2) as therapeutical targets for Malignant Epithelial Neoplasia, specifically for Oral Squamous Cell Carcinoma (OSCC)., Conclusion: The literature review and Bioinformatics analyses showed that ACE and ACE2 are interesting targets for OSCC treatment. Studies involving RAS and OSCC should be encouraged for experimental validation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.

Background: Understanding the biological processes underlying Pressure Ulcer (PU) is an important strategy to identify new molecular targets. Bioinformatics has emerged as an important screening tool for a broad range of diseases., Objective: This study aim of the current study is to investigate the protein-protein interaction in the PU context by bioinformatics., Methods: We performed a search in gene databases, and bioinformatics algorithms were used to generate molecular targets for PU based in silico investigation. Interactions networks between protein-coding genes were built and compared to skin., Results: TNFA, MMP9, and IL10 genes have higher disease-related connectivity than a connectivity general global. MAGOH, UBC, and PTCH1 as were leader genes related to skin. Ontological analysis demonstrated different mechanisms associated, such as response to oxidase stress., Conclusion: TNFA, MMP9, and IL10 are possible therapeutic targets for pressure ulcer. Additional investigation of cell post-transcriptional machinery should be investigated in PU., (Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of the current study is to investigate the association between E-cadherin methylation status, hypoxia and OSCC., Methods: HaCat and SCC9 cell lines were submitted to hypoxic treatment, followed by methylation profile analysis (MS-PCR) and analysis of the expression of mRNA gene E-cadherin (RT-PCR). Study group samples comprise individuals affected by potentially malignant lesions Potential Malignant Oral Lesion (PMOL, n=18) and oral squamous cell carcinoma (OSCC, n=28). The control group oral mucosa (OM, n=15) of patients with an oral mucocele. Cell migration ability was evaluated a scratch wound assay in SCC9 and HaCat cell lines RESULTS: E-cadherin mRNA expression in the cell lines SCC9 and HaCat was significantly reduced under hypoxia, regardless of the methylation profile, when compared to the control group. No differences in methylation profile of the E-cadherin were observed among the groups OM, PMOL and OSCC. HaCat and SCC9 presented increases in cell migration rates under hypoxia., Conclusion: The current study demonstrates that hypoxia reduces E-cadherin expression and increase cell migration, regardless of the methylation profile. Additionally, no differences in E-cadherin methylation patterns were observed among OM, PMOL and OSCC., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: Fibronectin type III domain containing 5 (FNDC5) and its protein product Irisin are therapeutic targets for obesity-associated disorders. Irisin plays an important role in energy regulation, inducing browning of white adipocytes, and improving obesity. We aimed to investigate the association between muscle Irisin expression and dietary quality., Methods: Twenty-eight female mice were divided into four groups and fed the following experimental diets for 60 days: standard diet (SD), high-carbohydrate diet (HCD), high-fat diet (HFD), and high-protein diet (HPD). We evaluated body weight, food intake, serum total cholesterol, triacylglycerol, and glucose. We also performed glucose tolerance and insulin sensitivity tests. Expression of FNDC5 was evaluated by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) of soleus muscle. Western blot was used to assess Irisin protein expression., Results: The major finding of the present study was that HFD and HCD were associated with a downregulation of FNDC5. In addition to these results, we noted a significant reduction in skeletal muscle Irisin level. HPD prevented reductions of both FNDC5 and Irisin levels, as well as increased brown adipose tissue, compared to the control group., Conclusions: In conclusion, we observed that the HPD type of diet can change both FNDC5 expression and Irisin levels. Thus, the HPD might be the most appropriate diet to achieve high amounts of Irisin, a target molecule for the treatment of obesity and its co-morbidities.

This is a cross-sectional study with a quantitative approach, establishing the epidemiological profile of people with physical disabilities resident in the municipality of Florianópolis, in the Southern Brazilian state of Santa Catarina, and analyzing it in relation to the public policies related to that population. The minimum sample was determined by a statistical calculation, considering the population of the municipality with disabilities, according to data from the 2010 Population Census. The data were collected using an electronic form installed in mobile devices and stored at an online provider. The data were analyzed and handled with the software Statistical Package for the Social Sciences. A total of 139 questionnaires were processed. A separation of the results was made using these categories: Individual attributes; Social attributes; and Characteristics related to disability. As well as the descriptive profile of the disabled people, the study analyses and discusses the distance, worldwide and in Brazil, between the proposals for public policies and the actual actions of care directed towards the rights of these people. The conclusion is that there is a fundamental need to act in relation to the real needs of this population and consolidate proposals for health promotion, health protection and health rehabilitation for them.

Pathogenesis of odontogenic tumors is not well known. It is important to identify genetic deregulations and molecular alterations. This study aimed to investigate, through bioinformatic analysis, the possible genes involved in the pathogenesis of ameloblastoma (AM) and keratocystic odontogenic tumor (KCOT). Genes involved in the pathogenesis of AM and KCOT were identified in GeneCards. Gene list was expanded, and the gene interactions network was mapped using the STRING software. "Weighted number of links" (WNL) was calculated to identify "leader genes" (highest WNL). Genes were ranked by K-means method and Kruskal-Wallis test was used (P<0.001). Total interactions score (TIS) was also calculated using all interaction data generated by the STRING database, in order to achieve global connectivity for each gene. The topological and ontological analyses were performed using Cytoscape software and BinGO plugin. Literature review data was used to corroborate the bioinformatics data. CDK1 was identified as leader gene for AM. In KCOT group, results show PCNA and TP53 . Both tumors exhibit a power law behavior. Our topological analysis suggested leader genes possibly important in the pathogenesis of AM and KCOT, by clustering coefficient calculated for both odontogenic tumors (0.028 for AM, zero for KCOT). The results obtained in the scatter diagram suggest an important relationship of these genes with the molecular processes involved in AM and KCOT. Ontological analysis for both AM and KCOT demonstrated different mechanisms. Bioinformatics analyzes were confirmed through literature review. These results may suggest the involvement of promising genes for a better understanding of the pathogenesis of AM and KCOT., Competing Interests: The authors declared no conflict of interest.

Background: Metformin is a biguanide, belonging to the oral hypoglycemic agents and is a widely used in the treatment of type 2 diabetes. Evidence indicate that Metformin inhibits cell proliferation in several human cancers and inhibits the Warburg phenomenon in tumor cells., Results: Low PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions. Metformin also reduced HIF-1α mRNA and protein levels. Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3., Objective: The present study aims to explore the effects of Metformin in hypoxic conditions. Specifically, we focused on pyruvate dehydrogenase (PDH), (hypoxia-inducible factor 1α) HIF-1α levels and the oral squamous cell carcinoma (OSCC) cell phenotype. Additionally, we also investigated a theoretical consequence of Metformin treatment., Methods: PDH levels in patients with OSCC and oral dysplasia were evaluated. Metformin was administered in vitro to test the effect of Metformin under hypoxic conditions. The results were complemented by Bioinformatics analyses., Conclusions: In conclusion, our current findings show that Metformin reduces HIF-1α gene expression and increases PDH expression. Metformin inhibits cell proliferation and migration in the OSCC cell line model. Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels. Interestingly enough, Metformin did not increase the mutant p53 levels under hypoxic conditions.

The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of GA on oral squamous cell carcinoma. In a second step to confirm theoretical results, migration, invasion, proliferation, and gene expression (Col1A1, E-cadherin, HIF-1α, and caspase-3) were performed under normoxic and hypoxic conditions. Our study indicated that treatment with GA resulted in the inhibition of cell proliferation, migration, and invasion in neoplastic cells. Observation of the molecular mechanism showed that GA upregulates E-cadherin expression and downregulates Col1A1 and HIF-1α expression, suggesting that GA might be a potential anticancer compound. In conclusion, the present study demonstrated that GA significantly reduces cell proliferation, invasion, and migration by increasing E-cadherin and repressing Col1A1.

Background: Skin cancer represents the most common worldwide malignancy. Angiogenesis is an important factor in tumor growth and metastasis. Given these facts, the purpose of the current study was to compare the levels of angiogenic proteins in the context of the most common malignant and premalignant skin lesions., Methods: Immunohistochemistry of CD31, HIF1A, VEGFR1 and VEGFR2 was performed in basal cell carcinoma (BCC), actinic keratosis (AK) and squamous cell carcinoma of the skin (SCCS)., Results: SCCS presented with increased levels of HIF1A, VEGFR1 and VEGFR2 in comparison to AK. In addition, SCCS also demonstrated increased levels of HIF1A to BCCLR or BCCHR. BCC presented with more vessels than AK. However, no correlation was observed among CD31, HIF1A, VEGFR1 and VEGFR2., Conclusions: SCCS presented with higher levels of HIF1A, VEGFR1 and VEGFR2, while BCC demonstrated an increased number of vessels in relation to AK. These data suggest that antiangiogenic therapy might be useful for skin cancer treatment., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Introduction: Matrix metalloproteinases (MMPs) are the major class of enzymes responsible for degradation of extracellular matrix components and participate in the pathogenesis of periapical inflammatory lesions. MMP expression may be regulated by DNA methylation. The purpose of the present investigation was to analyze the expression of MMP2 and MMP9 in periapical granulomas and radicular cysts and to test the hypothesis that, in these lesions, their transcription may be modulated by DNA methylation., Methods: Methylation-specific polymerase chain reaction was used to evaluate the DNA methylation pattern of the MMP2 gene in 13 fresh periapical granuloma samples and 10 fresh radicular cyst samples. Restriction enzyme digestion was used to assess methylation of the MMP9 gene in 12 fresh periapical granuloma samples and 10 fresh radicular cyst samples. MMP2 and MMP9 messenger RNA transcript levels were measured by quantitative real-time polymerase chain reaction., Results: All periapical lesions and healthy mucosa samples showed partial methylation of the MMP2 gene; however, periapical granulomas showed higher MMP2 mRNA expression levels than healthy mucosa (P = .014). A higher unmethylated profile of the MMP9 gene was found in periapical granulomas and radicular cysts compared with healthy mucosa. In addition, higher MMP9 mRNA expression was observed in the periapical lesions compared with healthy tissues., Conclusions: The present study suggests that the unmethylated status of the MMP9 gene in periapical lesions may explain the observed up-regulation of messenger RNA transcription in these lesions., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

It is estimated that 7.6 million people will die as a consequence of head and neck squamous cell carcinoma (HNSCC). Genetic predisposition has emerged as an important risk factor in the development and prognosis of HNSCC. Considering this, the aim of the current study is to assess whether codon 72 SNP of the TP53 gene (rs1042522) is associated with an increased odds ratio of developing HNSCC or with a worse prognosis in patients with HNSCC. Analysis of the rs1042522 in HNSCC patients and in control individuals. Differences between the case and control groups were determined using chi-squared tests. Multivariate analysis was performed to evaluate the odds ratio of HNSCC. Fussy C Means Clustering was to cluster HNSCC patients for survival analyses. Time of survival was calculated using the Kaplan-Meier estimator and comparing this to the log rank test. Statistical significance was set at p < 0.05. A total of 71.4 % of the Arg/Arg genotype were from HNSCC patients, while only 28.6 % of Arg/Arg genotype were found in the control group. Logistic regression demonstrated that the Arg/Arg genotype, smoking, and alcohol consumption increase the odds ratio of HNSCC. No association between TP53 codon 72 polymorphism and P53 expression. No association between rs1042522 and survival or prognoses was observed. This study identified that individuals carrying the arginine allele at rs1042522 have an increased odds ratio of HNSCC. However, no association between codon 72 SNP of the TP53 gene and HNSCC prognosis or P53 expression was observed.

Background: Nursing students on clinical placements as part of their professional training are routinely faced with situations involving ethical conflicts. The initial act of perceiving a situation as causing an ethical dilemma is the result of both the students' personal values, drawn from their culture and families, and of the professional knowledge and values that they have acquired through training and experience., Objectives: Nursing students' experiences on clinical placements in primary care settings were investigated in order to identify situations that they perceived as involving ethical conflict and describe the elements they took into consideration during their decision-making processes in these situations., Methods: The research design was qualitative descriptive case study. Around 50 students from three different intakes to a nursing degree answered a questionnaire and discussed it in focus groups., Ethical Considerations: The study was designed in accordance with the principles guiding research with human beings and was approved by the Human Research Ethics Committee., Results: Synthesised into two principal axes: (a) ethical conflicts in primary care, linked with the domains of working processes, professional nursing ethics and human and social rights and (b) students' decision-making processes - realisation, reflection and intervention., Conclusion: The student nurses saw themselves both as actors and spectators in situations involving ethical problems and demanding moral deliberation, demonstrating the ability to base their arguments soundly. They tended to emphasise the possibilities offered by dialogue and that different ethical values must be respected to find fair solutions to ethical problems., (© The Author(s) 2014.)

Introduction: Bioinformatics has emerged as an important tool to analyze the large amount of data generated by research in different diseases. In this study, gene expression for radicular cysts (RCs) and periapical granulomas (PGs) was characterized based on a leader gene approach., Methods: A validated bioinformatics algorithm was applied to identify leader genes for RCs and PGs. Genes related to RCs and PGs were first identified in PubMed, GenBank, GeneAtlas, and GeneCards databases. The Web-available STRING software (The European Molecular Biology Laboratory [EMBL], Heidelberg, Baden-Württemberg, Germany) was used in order to build the interaction map among the identified genes by a significance score named weighted number of links. Based on the weighted number of links, genes were clustered using k-means. The genes in the highest cluster were considered leader genes. Multilayer perceptron neural network analysis was used as a complementary supplement for gene classification., Results: For RCs, the suggested leader genes were TP53 and EP300, whereas PGs were associated with IL2RG, CCL2, CCL4, CCL5, CCR1, CCR3, and CCR5 genes., Conclusions: Our data revealed different gene expression for RCs and PGs, suggesting that not only the inflammatory nature but also other biological processes might differentiate RCs and PGs., (Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)