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Background: Recurrent aphthous stomatitis (RAS) is characterized by recurrent episodes of oral ulceration in an otherwise healthy individual. Some reports in the literature indicate that RAS may have immunological, psychological, genetic and microbiological bases. The purpose of the present study was to investigate the possible association between interleukin-1 β (IL-1 β) +3954 (C/T) genetic polymorphism and RAS in a sample of Brazilian patients. Subjects and methods: Sixty-two consecutive subjects affected by minor and major forms of RAS and 62 healthy volunteers were genotyped at IL-1 β (+3954). The chi-squared test was used for statistical analysis. Results: A significant increase in the high production of IL-1 β genotype CT was observed in the group with RAS ( P = 0.01). After stratifying RAS patients according to the mean number of lesions per episode, a significant difference was only observed between patients with ≥3 lesions in each episode and control. Conclusion: There is an increased frequency of polymorphism associated with high IL-1 β production in RAS patients. [ABSTRACT FROM AUTHOR]

Burning mouth syndrome (BMS) is a chronic pain syndrome that encompasses all forms of burning sensations in the oral cavity when the oral mucosa is clinically normal. Neural, psychologic, and cytokine factors may be implicated in the pathogenesis of BMS. There are no studies of genetic factors associated with psychologic behavior and cytokine pain sensitivity in BMS patients. The purpose of the present study was to investigate a possible association between functional genetic polymorphisms, +3954 (C/T) interleukin-1beta, and the polymorphic site on promoter region of the serotonin transporter gene (5-HTTLPR) in a sample of Brazilian patients. Thirty patients affected by BMS and 31 healthy volunteers were genotyped for 5-HTTLPR and IL-1beta gene. The chi-squared test was used for statistical analysis. There was no statistical difference in 5-HTTLPR genotypes between the case and control groups (P = .60), however a significant increase was observed in the IL-1beta high production genotype CT in BMS subjects (P = .005). In conclusion, the present study shows association between BMS and IL-1beta high producer genotype. PERSPECTIVE: This article shows evidence that genetic polymorphisms associated with IL-1beta high production genotype are implicated on the pathogenesis of BMS. The modulation of IL1beta production may be an interesting tool in BMS management. [ABSTRACT FROM AUTHOR]

Investigate the frequency of herpes simplex virus type 1 (HSV-1) reactivation in the oral cavity of seropositive patients with previous history of recurrent herpes labialis (recrudescent group) compared with those without any history of recrudescent lesions (asymptomatic HSV-1 infection). In addition, the relation between recrudescence and the presence of the virus in the saliva was assessed.Fourteen individuals with previous history of herpes labialis (recrudescent group) and 11 HSV-1 seropositive asymptomatic volunteers were included in the study. Swabs were performed periodically in all subjects and the presence of HSV-1 DNA was identified by nested PCR.All the 25 subjects enrolled in the study, revealed at least one positive swab for HSV-1. The frequency of HSV-1 positivity in the group with recrudescent herpes labialis was not statistically different from the other group. Ten subjects of the recrudescent group presented with herpes labialis at least once during the study.HSV-1 shedding in the oral cavity occurs independently of herpes labialis recrudescence. [ABSTRACT FROM AUTHOR]

Considering that hMSH2, hMLH1 and p53 are important in maintaining genomic stability of the oral mucosa epithelium, the purpose of the present study was to investigate the immunolocalization of these proteins in the epithelium of the oral mucosa of patients submitted to bone marrow transplantation (BMT) compared with controls. Twenty-one samples of lip biopsies from BMT recipients were retrieved. Twenty samples of normal lower labial mucosa associated with mucocele in non-transplanted patients were included as control group. The streptavidin­biotin complex stain was used to detect the human DNA mismatch repair proteins hMSH2, hMLH1 and p53 protein. RESULTS: The main findings demonstrated that the mean number of suprabasal epithelial cells positive for MSH2 was statistically higher than the control group. The immunostaining of hMLH1 and p53 at the basal and suprabasal epithelial layers were statistically higher in the oral labial mucosa of the BMT patients compared with controls. CONCLUSION: The present study shows that oral epithelial cells of BMT patients show increased immunolocalization of the DNA repair related proteins. [ABSTRACT FROM AUTHOR]

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.)

Objective: The current study aims to investigate the safety and efficacy of using calcium hydroxyapatite (CaHA) versus CaHA associated with hyaluronic acid (HA) for forehead volume replacement and contour restoration without forehead irregularities., Methods: This interventional study involved 132 participants in a two-arm, parallel, double-blind trial for forehead treatment using the supraperiosteal technique. Group A received CaHA, and Group B received a combination of CaHA and HA as filler materials. Follow-up assessments occurred at 30 and 180 days, incorporating the 5-point Global Aesthetic Improvement Scale (GAIS) and photographic analysis for forehead volume replacement, contour restoration, and without forehead irregularities. Safety assessments included monitoring adverse events, particularly nodules., Results: The study included all 132 enrolled patients who completed the trial. Applying CaHA in combination with HA resulted in a statistically significant improvement in both GAIS scale scores and the reduction of forehead irregularities. The total incidence of nodules was 3.7%. Group A had four times more occurrences of nodules than Group B. Furthermore, Group B exhibited lower rates of forehead irregularities following the treatment compared to Group A., Conclusion: The supraperiosteal application of CaHA and HA for forehead treatment demonstrates superior efficacy in addressing signs of aging compared to the isolated use of CaHA., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

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.)

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: 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.)

Sestrins (SESNs) are a family of evolutionarily conserved proteins among mammals. They have several body homeostatic functions such as antioxidant, metabolic, and anti-aging, and are required to regenerate hyperoxidized forms of peroxiredoxins and reactive oxygen species. Sestrin 2 has been studied as a therapeutic agent in obesity treatment. Gallic acid (GA) is a triphenolic compound with beneficial biological activities including anti-inflammatory, antidiabetic, antihypertensive, and antioxidant effects. Recent studies demonstrated the GA's ability to reduce body weight gain and improve glycemic parameters. In this sense, the present study aims to investigate the GA activating potential of Sestrin using the molecular docking method. The 3D structure of gallic acid was retrieved from the NCBI PubChem database and the chemical structure of the Sestrin2 protein from the RCSB Protein Data Bank (5DJ4). The docking calculus was performed via UCSF Chimera and AutoDock Vinaprograms. The results showed that amino acids Arg390, Glu451, Trp444, Thr386, Arg448, Thr374, Tyr375, Asn376, Thr377, Leu389, His454, Ser450, His86, and Val455 are very important for GA stabilization, resembling the interactions that permit Leucine to activate SESN2. In this context, the obesity therapeutic property of GA can be understood from a Sestrin activating process through amino acid metabolism., 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 © 2023 Elsevier B.V. All rights reserved.)

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: Lychnophora ericoides Mart, also known as the Brazilian arnica or fake arnica, belongs to the Asteraceae family. Leaves and roots are used in alcoholic and hydroalcoholic preparations for the treatment of wounds, inflammation, and pain., Purpose: The present study aimed to investigate the effects of L. ericoides ethanolic extract (EELE) on cutaneous wound healing and the mechanisms of action involved., Methods: A total of 72 C57BL/6 mice were randomly divided into four groups of six animals each. An excisional wound was made in the dorsal region of each mouse. The test groups were topically treated with the vehicle, a positive control commercial reference drug, EELE ointment (5%), and EELE ointment (10%). The treatments were applied over 14 days. The wound area was measured every two days to verify the wound closure kinetics. On days 3, 7, and 14 the wound tissue samples were processed for Hematoxylin and Eosin, Masson-Trichrome, and Toluidine blue staining. The expression of renin-angiotensin system (RAS) components, the vascular growth factor-A (VEGF-A), the basic fibroblast growth factor (FGF-2), and type I collagen genes were evaluated. Phytochemical analyses were performed using HPLC-DAD and HPLC-MS/MS., Results: The EELE (10%) significantly reduced the wound area compared to the treatments used for the other groups. Histological analysis demonstrated that wounds treated with L. ericoides for 14 days developed improved anatomical skin features, healed with hair follicles and sebaceous glands, increased collagen production and angiogenesis, and decreased the number of mast cells at the injury site. Real-time PCR data demonstrated that groups treated with EELE (10%) showed increased Type I collagen, VEGF-A, FGF-2, and AT 1 R and decreased ACE II and receptor MAS. The healing action of L. ericoides may be related to the presence of phenolic compounds, such as phenolic acids, chlorogenic acid derivatives, and C-glycoside flavonoids., Conclusion: Topical treatment with EELE increases important factors for wound healing: FGF, VEGF, collagen formation, and the expression of the proliferative axis of the renin-angiotensin system. For the first time, the present study shows the healing action of L. ericoides at the molecular level in an animal model. This process can be used as an alternative therapy for wound healing and the development of herbal therapy., 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 © 2023 Elsevier GmbH. All rights reserved.)

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.

To evaluate the effects of Light-Emitting Diode (LED) irradiation on the expression of thermogenesis and lipogenesis-associated markers in adipose tissue and metabolic parameters of obese mice. Twenty-four male mice were divided into four groups: i) ST fed standard diet; ii) HCD fed hyperglycemic diet; iii) LED + I fed hyperglycemic diet and irradiated with LED in the interscapular region; iv) LED + A fed hyperglycemic diet and irradiated with LED in the abdominal region. The first phase of the study comprehended the induction of obesity for 12 weeks. Next, the animals were submitted to six irradiation sessions (days 1, 3, 7, 10, 14, and 21) using a 660-nm LED (5.77 J/cm 2  at 48,1 mW/cm 2 ). Anthropometric, biochemical, and histological parameters and the expression of thermogenesis and lipogenesis-associated markers were assessed in adipose tissue. There was diminished weight gain between the HCD and LED + A groups (ST: 0.37 ± 0.65; HCD: 3.10 ± 0.89; LED + I: -1.26 ± 0.83; LED + A: -2.07 ± 1.27 g; p < 0.018). There was a 33.3% and 23.8% reduction in epidydimal adipose tissue weight and a 25% and 10.7% in the visceral adiposity for the LED + I and LED + A groups, respectively, when compared with HCD. There was a decreased accumulation of fat droplets in adipose tissue in LED + A and LED + I groups. Additionally, LED irradiation was associated with increased mRNA expression of uncoupling protein 1 (UCP1) in the brown adipose tissue (ST: 2.27 ± 0.19; HCD: 1.54 ± 0.12; LED + I: 2.44 ± 0.22; p = 0.014) and decreased fatty acid synthetase (FAS) expression in epidydimal adipose tissue (ST: 0.79 ± 0.13; HCD: 1.59 ± 0.13; LED + A: 0.85 ± 0.04; p = 0.0008). LED treatment improved anthropometric parameters, possibly associated with the histological alterations, thermogenesis and lipogenesis markers in white adipose tissue, and expression modulation in brown adipose tissue., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Maternal obesity and dietary style in the pregnancy-lactation period may result in long-term effects on the metabolic health of the offspring, thus increasing the risk of diseases, such as obesity, diabetes, and cardiovascular diseases. Curcumin is a natural polyphenolic compound that has beneficial properties on metabolism. Accordingly, this study is intended to evaluate the effects of curcumin supplementation in pregnant and lactating female mice on the anthropometric, metabolic and molecular parameters of the offspring fed a hyperglycemic diet. The study was conducted with 24 male mice randomized into three groups: i) control group (SD) originating from dams fed a standard diet; ii) hyperglycemic group (HGD) originating from dams fed a hyperglycemic diet; iii) curcumin group (CUR) originating from dams fed a hyperglycemic diet and supplemented with curcumin in the pregnancy-lactation period. All offspring groups were fed a hyperglycemic diet for 12 weeks. Anthropometricand biochemical parameters were measured, as well as the expression of thermogenesis-associated markers in the interscapular brown and inguinal white adipose tissues. The results showed less weight gain in the CUR group, with a concomitant reduction in food consumption compared to the HGD group. Biochemical parameters indicated lower levels of total cholesterol, glucose, and insulin for the CUR group, in addition to improved glucose tolerance and insulin sensitivity. The molecular evaluation indicated increased mRNA expression levels of UCP1 and PRDM16 in the brown and white adipose tissues. It is concluded that curcumin supplementation in the pregnancy-lactation period in dams with diet-induced obesity may lead to improvements in the offspring's metabolic phenotype, even if they are submitted to an obesogenic environment, possibly via thermogenesis activation., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

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.)

The present study aimed to determine whether cumulus cells (CC) biopsy, acquired before or after in vitro maturation (IVM), presents similar gene expression pattern and if would compromises oocyte quality. First, immature cumulus oocyte complexes (COCs) were distributed: (1) maturated in groups (control); (2) individually maturated, but not biopsied; (3) subjected to CC biopsy before maturation and individually matured; (4) individually matured and submitted to CC biopsy after maturation; (5) individually matured and CC biopsied before and after maturation. Secondly, candidate genes, described as potential markers of COCs quality, were quantified by RT-qPCR in CCs before and after IVM. After in vitro fertilization (IVF), zygotes were tracked and sorted regarding their developmental potential: fully developed to embryo, cleaved and arrested, and not-cleaved. The COC’s biopsy negatively affects embryo development (p < 0.05), blastocyst cell number (p < 0.05), and apoptotic cell ratio (p < 0.05), both before and after IVM. The PTGS2, LUM, ALCAM, FSHR, PGR, SERPINE2, HAS2, and PDRX3 genes were differentially expressed (p < 0.05) on matured CCs. Only PGR gene (p = 0.04) was under-expressed on matured CCs on Not-Cleaved group. The SERPINE2 gene was overexpressed (p = 0.01) in the Cleaved group on immature CCs. In summary, none of the selected gene studies can accurately predict COC’s fate after fertilization.

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.)

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.)

Individual embryo culture is the only strategy that allows the tracking of embryos throughout the culture period. However, this procedure leads to lower embryo development. This study aimed to evaluate different alternatives to improve embryo development in a single in vitro production system. First, embryo production was compared between individual cultures on a 20 μL droplet and Cell-Tak® system. Then, various concentrations of folic acid were tested for use in combination with insulin-transferrin-selenium (ITS). To determine the concentration, embryos were analyzed not only by development but also by their methylation status. Finally, the supplementation of individual culture media with ITS and/or folic acid was evaluated. The results showed that embryos cultured in the Cell-Tak® system presented lower blastocyst rates than the microdroplets system. When the concentration of folic acid was tested, 20 μM and 500 μM presented a higher level of insulin-like growth factor (IGF2) DNA methylation pattern compared to control, suggesting that in vitro conditions alter DNA methylation pattern in that region and folic acid reestablishes the pattern. However, when it was used in an individual culture system, folic acid did not improve embryo development. Conversely, ITS which is composed of three important components, proved to be an alternative to individual embryo culture, improving embryo rates, showing similar rates to grouped culture embryos. Since Folic Acid change epigenetic profile, additional studies are needed to evaluate its use in IVP culture systems., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Neutrophil extracellular traps (NETs) are a recently discovered neutrophil defense mechanism which modulates several inflammatory conditions contributing to metabolic profile alterations. Therefore, the present study aimed to evaluate the production of NETs in obese patients and mice, verifying the possible mechanisms associated with the release of NETs by the adipose tissue., Methods and Results: The present study investigated NETs production in human adipose tissue and also showing the neutrophils using intravital microscopy in mouse epididymal adipose tissue. Blood and white adipose tissues were obtained from eutrophic and obese individuals and from mice. Lipid, glycemic and leukocyte profiles were evaluated, as well as the levels of NETs and its markers. Bioinformatics and proteomics analyses were performed and the identified key proteins were measured. The main findings showed that the inflammatory markers interleukin-8 (IL-8), heat shock protein 90 (HSP90) and the E1 heat shock protein family (HSPE1) can be modulated by the NETs levels in obesity. Obesity has also been associated with increased cholesterol, glucose intolerance, ionic calcium and NETs. We also observed an increase in catalase and a decreased superoxide dismutase activity. Bioinformatics and proteomics analyses revealed that IL-8, HSP90 and HSPE1 were associated with obesity, inflammation and NETs release., Conclusions: In conclusion, the present study shows an increase in NETs production during obesity associated with important inflammatory markers in adipose., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: The present study aimed to develop and evaluate a new dairy by-product nutritional supplement with Buriti fruit to improve malnutrition in mice and elderly woman., Background: Malnutrition is a prevalent problem in the elderly; therefore, oral dietary supplementation is an important strategy to reduce this health problem incidence., Objective: The present study evaluated the effects of a low-cost food supplement, made from byproducts of the dairy and fruit industry in the Brazilian Cerrado (Buriti), on the nutritional status and on the recovery of the metabolic profile of malnourished animals and elderly women., Methods: In the pre-clinical phase, Swiss mice were divided into six groups and subjected to malnutrition and renutrition. The clinical phase was carried out with 25 elderly women residing in a long-term institution, aged ≥ 65 years and with malnutrition or risk of malnutrition., Results: The main results showed improvements in anthropometric parameters and an increase in serum albumin levels, in addition to lipid profile improvement in the preclinical phase and an increase in the red blood cells and hemoglobin in the clinical phase., Conclusion: The supplement based on Buriti was able to reverse malnutrition promoting improvements in anthropometric and biochemical parameters., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

Institutionalization has been associated with social isolation, psychological and cognitive changes, and decreased levels of physical activity in older adults., Objectives: The aim of this study was to estimate the prevalence of dementia, mild cognitive impairment (MCI), and functional dependence in older adults dwelling in two different Brazilian long-term care facilities (LTCFs)., Methods: This is a cross-sectional study with 185 older people of both sexes, aged 60 years or over, residing in two LTCFs in the city of Montes Claros-MG, Brazil. The diagnosis of MCI and dementia was performed using the Diagnostic and Statistical Manual of Mental Disorders ., Results: Prevalence rates of dementia, MCI, and functional dependence in institutionalized older participants were 62.3, 15.1, and 78.9%, respectively. There was a significant reduction of the Mini-Mental State Examination scores according to the increase of the institutionalization period in LCTFs and the age of older adults (p<0.001)., Conclusions: Prevalence of dementia and functional dependence of older adults residing in LTCFs exhibited higher rates compared to the other older population worldwide. A higher institutionalization period is related to a greater cognitive decline., Competing Interests: Disclosure: The authors report no conflicts of interest.

It is well-established that in vitro culture affects quality, gene expression, and epigenetic processes in bovine embryos and that trophectoderm cells are the most susceptible to abnormalities. These changes have been reported as the main factors responsible for losses observed after transfer of in vitro-produced embryos. The present study aimed to investigate the effect of an in vitro system on bovine embryo transcriptional profiles on D14 of development. Two groups were used-one with embryos produced in vitro until D7 (day 7; VT group) and another with embryos produced in vivo by hormonal stimulation, with embryos collected on D7 (VV group). D7 embryos at similar developmental stages from both treatments were transferred to recipient uteri and recollected on D14. From D14 embryos of both treatments, trophoblast samples were removed by biopsy for sexing and transcriptome analyses. Embryos were sexed by polymerase chain reaction (PCR), and only males were used for RNA sequencing. In total, 29,005 transcripts were expressed, from which 900 were differentially expressed, but only 29 genes were significantly differentially expressed. In addition, 20 genes were found uniquely for VV and 27 for VT. These findings suggested that although the uterine environment minimized transcriptional differences, it was not able to make trophoblasts from the in vitro embryos similar to the in vivo ones. The few genes exhibiting differences are in control of important events that may be responsible for embryonic losses occurring during the first period of gestation., (© 2021. The Society for In Vitro Biology.)

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.)

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.)

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Background: The microbiome is now known for its important role in whole-body homeostasis. A dysbiosis of the normal microbiota is correlated with metabolic disorders. In this sense, the search for compounds able to modulate the microbiome is needed. Resveratrol, a natural compound found in grapes seems to be a promising candidate., Objective: In this study, our motivation was to evaluate the effects of the association between Resveratrol and Lactococcus lactis, a probiotic, on the composition of the gastrointestinal microbiota and body weight of mice., Methods: Twenty female mice were divided into 4 groups: (1) standard diet, (2) standard diet plus Lactococcus lactis, (3) standard diet plus resveratrol, and (4) standard diet plus Lactococcus lactis and resveratrol. At the end of the treatment period, samples of blood, mucus, stomach, and small and large intestines were collected for analysis. Total levels of Immunoglobulin A and Immunoglobulin E, Lac+ and Lac- bacteria and Lactobacillus were measured., Results: The main results indicate that the association between resveratrol and probiotics was able to decrease mice body weight, as compared to the other groups, in addition to decrease the number of Lac- bacteria and increasing the number of Lac+ bacteria. The levels of secretory IgA were also decreased, compared to the animals treated with only probiotics or resveratrol., Conclusion: We observed potential synergism between Resveratrol and Lactococcus lactis mainly in modulating the stomach and intestinal microbiota., (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.)

Background: Obesity and non-alcoholic fatty liver disease (NAFLD) have been increasing at an alarming rate worldwide. Bifidobacterium longum (BL), a common member of the human gut microbiota, has important health benefits through several mechanisms., Objectives: We evaluated the BL supplementation effects on body metabolism and renin-angiotensin components hepatic expression in mice fed a high-fat diet., Methods: Thirty-two male mice were divided into four groups: standard diet + placebo (ST), standard diet + Bifidobacterium longum (ST + BL), high-fat diet + placebo (HFD) and high-fat diet + Bifidobacterium longum (HFD + BL). Following the obesity induction period, the ST + BL and HFD + BL groups were supplemented with Bifidobacterium longum for 4 weeks. Then, body, biochemical, histological and molecular parameters were evaluated., Results: HFD + BL mice had a significant decrease in adipose tissue mass and blood glucose levels, as well as a significant reduction in blood glucose during an intraperitoneal glucose tolerance test. The treatment also resulted in reduced levels of total cholesterol and hepatic fat accumulation. Moreover, we observed an increase in angiotensin converting enzyme 2 (ACE2) and Mas receptor (MASR) expression levels in BL-treated obese mice., Conclusions: These data demonstrate that BL may have the potential to prevent obesity and NAFLD by modulating the mRNA expression of renin-angiotensin system components.

Background: Malnutrition induced by dietary restriction produces several metabolic changes that affect body weight, the digestive system, and annex organs, including the liver. Malnutrition generates an inflammatory state and increases oxidative stress. The liver is one of the body vital organs, becoming necessary to analyze the impact of food supplementation on the repair of possible changes that may occur in this organ due to malnutrition., Aims: To evaluate the effects of a low-cost supplementation derived from Buriti and dairy byproducts on liver recovery in malnourished mice, focusing on the expression of oxidative stressrelated genes, as well as biochemical and histological parameters., Methods: Swiss mice were divided into six groups and submitted to two treatment phases: food restriction, for malnutrition onset; and renutrition, with mice being fed with different diets., Results: Our results indicate that dietary supplementation was successful in recovering liver damage caused by malnutrition in animal models. The new supplement has been shown to recover liver damage with similar or superior results compared to the commercial reference supplement on the market., Conclusion: Our work presents a new composition of low cost food supplement based on buriti and dairy by-products, proven to be effective in the malnutrition treatment of malnutrition. The improvements were proven through the recovery of body weight, reduction of inflammation and oxidative stress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Obesity is a serious health problem that dysregulate Renin-Angiotensin System (RAS) and intestinal microbiota., Objective: The present study aimed to evaluate the Angiotensin-(1-7) [ANG-(1-7)] oral formulation effects on obese mice intestinal microbiota., Methods: Mice were divided into four groups: obese and non-obese treated with ANG-(1-7) and obese and non-obese without ANG-(1-7) during four weeks., Results: We observed a significant decrease in the fasting plasma glucose, total cholesterol, triglycerides, and Low-density lipoprotein levels and increased High-density lipoprotein in animals treated with ANG-(1-7). The histological analysis showed intestinal villi height reduction in mice treated with ANG-(1-7). Additionally, increased Bacteroidetes and decreased Firmicutes (increased Bacteroidetes/ Firmicutes ratio) and Enterobacter cloacae populations were observed in the High-Fat Diet + ANG-(1-7) group. Receptor toll-like 4 (TLR4) intestinal mRNA expression was reduced in the HFD+ANG-(1-7) group. Finally, the intestinal expression of the neutral amino acid transporter (B0AT1) was increased in animals treated with ANG-(1-7), indicating a possible mechanism associated with tryptophan uptake., Conclusion: The results of the present study suggest for the first time an interaction between oral ANG-(1-7) and intestinal microbiota modulation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Physical activity is a complex behavior influenced by sociodemographic and clinical factors. A better understanding of the relationships between these factors is essential to better understanding their influence on physical activity. The objective of this study was to examine the association between socioeconomic status, age, body fat, and depressive symptoms and level of physical activity among adults. We conducted a cross-sectional population-based study with 808 individuals to examine the interrelations between the above factors and their influence on level of physical activity using path analysis. Age had a significant direct negative effect on level of physical activity (β = -0.113, p < 0.004) and a significant positive effect on body fat (β = 0.376, p < 0.001). Depressive symptoms were negatively influenced by socioeconomic status (β = -0.126, p < 0.001) and positively influenced by age (β = 0.244, p < 0.001) and body fat (β = 0.169; p < 0.004). Socioeconomic status, body fat and depressive symptoms did not directly influence level of physical activity. This study concludes that level of physical activity declines with advancing age.

Aims: The aim of the present study was to evaluate the oral resveratrol effects associated with diet and physical training changes on anthropometric and biochemical parameters., Main Methods: 25 individuals aged from 30 to 60 years old; with Body Mass Index (BMI) ≥ 30 kg/m 2 were included in the study. Following the primary evaluation (anthropometric and clinical), the patients were randomly divided into 2 groups: (1) Placebo: Physical activity program + Diet + Placebo; (2) Resveratrol: Physical activity program + Diet + Resveratrol (RVS) (250 mg/day) for three months. Anthropometric and biochemical parameters were evaluated at baseline and after the treatment period., Key Findings: The main findings showed that the resveratrol supplementation improved total cholesterol (TC), High-density Lipoprotein cholesterol (HDL-c), Very-low density Lipoprotein cholesterol (VLDL-c), urea, creatinine and albumin serum levels., Significance: These findings indicate that this polyphenol may be an option to potentiate the beneficial effects induced by dietary and physical activity programs in the Metabolic Syndrome (MetS) treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Renin-Angiotensin System (RAS) is an important peptide cascade involved in physiological processes. RAS homeostasis disruption produces several cardiovascular and metabolic disorders, such as arterial hypertension, atherosclerosis, acute myocardial infarct, obesity, diabetes, metabolic syndrome and increases gastrointestinal tract (GIT) cell proliferation. Angiotensin (Ang)-(1-7) peptide is the main RAS counter-regulatory axis effector. It is formed from ACE2 enzyme and acts mainly through Mas receptor (MasR). In this context, the aim of the present study was to evaluate alterations in small intestine morphology and intestinal microbiota composition in MasR knockout C57BL/6 mice. We analyzed glucose tolerance; insulin sensitivity and blood collected for biochemical parameters as well as small intestine tissues samples for immunohistochemistry. mRNA and bacteria gDNA expression evaluation. mRNA expression was evaluated by qRT-PCR for TLR4, PI3K and AKT. The main results showed that Mas-R-knockout mice presented lower body weight. MasR-knockout mice also presented increased fasted blood glucose and total cholesterol with reduced HDL, lower glucose tolerance and impaired insulin sensitivity. Increased intestinal mucosa length, increased intestinal villi, reduced Lieberkühn crypt depth. The increased expression of cell proliferation markers Ki-67 and Cyclin D1 and increased TLR4, PI3K and AKT expressions were observed with augmented Bacteroidetes and decreased amount of Firmicutes. That results suggests that MasR deletion generated changes in intestinal microbiota, possibly due to a lower neutral amino acids absorption followed by a compensatory increase in intestinal villi length associated with disbiosis and LPS overproduction that ultimately lead to proliferation and cell inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest/ disclosure(s)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ethnicity is an important determinant of blood pressure levels, being black individuals affected more than any other ethnic group. Arterial stiffening, an independent risk factor for hypertension, is also influenced by ethnicity. However, whether black individuals from different continents would have different patterns of arterial stiffening is still unknown. Thus, the authors aimed to compare pulse wave velocity (PWV) in black subjects living in Angola and Brazil. A total of 677 black individuals from two independent cross-sectional studies conducted in Brazil and Angola were included in this analysis. Carotid-to-femoral PWV was measured following the same protocols for both studies, as well as clinical and anthropometric variables. Adjusted PWV was higher in Brazilian blacks than in Angolans, regardless of sex (men from Brazil: 10.7 ± 1.8 vs men from Angola: 9.9 ± 1.8 m/s, P < .001; women from Brazil: 10.3 ± 1.5 vs women from Angola: 9.2 ± 1.3 m/s, P < .001). Although the cf-PWV was higher in Brazilian blacks, the age-related increase in cf-PWV was higher in Angolan men compared to Brazilians, but not in women. SBP showed the strongest association with cf-PWV, regardless of sex and country. However, age was associated with cf-PWV in all groups, except in Brazilian men. Our results clearly show a difference in PWV between two black populations, and highlight for sex differences in the hemodynamic parameters that might affect blood pressure levels in these populations., (©2020 Wiley Periodicals LLC.)

BACKGROUND To determine the magnitude and temporal trends of deaths due to congenital heart disease (CHD) in Pernambuco between 1996 and 2016. METHODS This was an ecological, time-series study, involving all cases of deaths from congenital cardiovascular malformations in the state of Pernambuco, from 1996 to 2016, using data from DATASUS, SINASC and SIM. RESULTS There were 3,584 deaths from congenital cardiovascular malformations amongst individuals aged 0 to 14 years, of which 81.94% were concentrated in children aged under one year. The infant mortality rate (IMR) presented a linear growth trend of 0.4645 per year (p <0.01). The cause-of-death code Q24 (other congenital malformations of the heart) was present in 72.54% of the death records and 48.17% of the deaths occurred in infants aged between 28 and 364 days of life. The highest occurrence of deaths was identified in children with low birth weight (500 and 1,499g), male, premature, children of mothers without schooling, in deliveries at home (p <0.05). CONCLUSIONS Congenital heart disease still represents a public health problem as a cause of death, particularly in the first year of life, with IMR in a linear growth trend. Deaths from CHD were more prevalent in male children, born prematurely, with low birth weight, born to mothers with low schooling and deliveries without medical care.

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.

In the present study, four experimental groups were used: fresh embryos, cultured during in vitro maturation and in vitro culture in media supplemented with bovine serum albumin (BSA) (fresh BSA) or fetal bovine serum (FBS) (fresh FBS); and two groups of cryopreserved and thawed embryos, produced under the same conditions (frozen BSA and frozen FBS). Experiment 1 evaluated the protein source effect on embryo development and response to cryopreservation. At day 7, half of the expanded blastocysts (Bx) from each group were cryopreserved and warmed and the other half were used as controls. After warming, embryos were incubated under the same conditions for 48 hours, and the hatching rate was measured at 24 and 48 hours. The total and the apoptotic cell numbers were measured in a subset of Bx after 24 hours. Experiment 2 used the Bx of experiment 1 to compare the expression of KRT8 , PLAC8 , FOSL1 , HSP1A1 , and HSPA5 genes in hatched blastocysts at 24 and 48 hours for all groups. The FBS group showed a higher percentage ( p  < 0.05) of embryos (42.8% vs. 27.9%) and higher rates of Bx (75.0% vs. 63.8%) on day 7, compared with the BSA group. At 24 hours postwarming, the fresh FBS group showed the highest hatching rate ( p  < 0.05) in comparison with other treatments. However, at 48 hours, the hatching rate was similar ( p  > 0.05) among groups: fresh FBS (68.1% ± 23.3%), fresh BSA (70.0% ± 31.0%), frozen FBS (39.2 ± 27.1), and frozen BSA (38.2 ± 23.9). After 24 hours, frozen BSA showed a higher number of cells compared with frozen FBS ( p  < 0.05). The expression of the PLAC8 gene was higher ( p  < 0.05) in fresh BSA embryos compared with frozen FBS embryos at 24 hours. In the present study, BSA replacement reduced embryo development, but did not affect the response to cryopreservation. However, upregulation of the PLAC8 gene suggests that embryos cultured in BSA might have better quality to support further development.

Introduction: Gallic acid (GA) is a natural endogenous polyphenol found in a variety of fruits, vegetables and wines, with beneficial effects on the energetic homeostasis., Aim: The present study aimed to investigate oral gallic acid effects on liver steatosis and hepatic lipogenesis markers in obese mice evaluating new possible molecular related mechanisms., Methods: Twenty-four Swiss male mice were divided into four groups and fed for 60 days with standard diet (ST), standard diet plus gallic acid (ST + GA), high-fat diet (HFD), and high-fat diet plus gallic acid (HFD + GA). We evaluated the relationship between body weight, food intake and serum levels of total cholesterol, triglycerides, insulin, aspartate and alanine transaminases. Liver histology was analyzed by hematoxylin and eosin staining. These results were accompanied by bioinformatics analyses. The acetyl-CoA carboxylase (ACC), sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was assessed by quantitative real-time reverse transcriptase PCR (qRT-PCR)., Results: The main findings of the present study showed that GA reduced liver steatosis, body weight and plasma insulin levels. Analyzes of hepatic steatosis related genes expression showed that ACC and FAS mRNA were significantly suppressed in liver of HFD + GA mice. These data was corroborated by bioinformatics analysis., Conclusion: These data suggest an important clinical application of GA in the prevention and treatment of liver diseases., Competing Interests: Declaration of competing interest There are no conflicts of interests. JNS, AFP, SHSS the conception and design of the study, JNS drafting the article, JMOA, DFL, EMS acquisition of data, or analysis and interpretation of data, AMBP, JPL, MFSVD, RSMJ, ALSG, revising it critically for important intellectual content., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Aims: The aim of the presente study was to examine the effects of oral gallic acid (GA) administration on the brown adipose tissue of obese mice fed with high-fat diet. New mechanisms and interactions pathways in thermogenesis were accessed through bioinformatics analyses., Main Methods: Swiss male mice were divided into four groups and fed during 60 days with: standard diet, standard diet combined with gallic acid, high-fat diet and high-fat diet combined with gallic acid. Body weight, food intake, and blood parameters (glucose tolerance test, total-cholesterol, high-density low-c, triglyceride and glucose levels) were evaluated. Brown and subcutaneous white adipose tissue histological analysis were performed. SIRT1 and PGC1-α mRNA expression in the brown adipose tissue were assessed., Key Findings: Our main findings showed that the gallic acid improved glucose tolerance and metabolic parameters. These results were accompanied by bioinformatics analyses that evidenced SIRT1 as main target in the thermogenesis process, confirmed as increased SIRT1 mRNA expression was evidenced in the brown adipose tissue., Significance: Together, the data suggest that the gallic acid effect in brown adipose tissue may improve body metabolism, glucose homeostasis and increase thermogenesis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.)