Effects of gallic acid and physical training on liver damage, force, and anxiety in obese mice: Hepatic modulation of Sestrin 2 (SESN2) and PGC-α expression.

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.

Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial.

BACKGROUND: Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. METHODS: The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. FINDINGS: From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69-2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61-2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04-0·95; p=0·044). INTERPRETATION: Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. FUNDING: European Community's 7th Framework Programme.

Older adults, appendicular anthropometric measurements, and poor functional performance are predictors of sarcopenia in individuals with head and neck squamous cell carcinoma.

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.

Middle cerebral artery blood velocity and cognitive function after high- and moderate-intensity aerobic exercise sessions.

This crossover study explored the acute effect of a session of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on middle cerebral artery (MCA) variables such as cerebral blood velocity, pulsatility index (PI) and resistivity index (RI) through transcranial Doppler (TCD), and cognitive function (CF - verbal fluency and Digit Span) in healthy young adults. Participants (26 healthy young adults, 13 women, 24 ± 3 years) underwent two different randomized exercise sessions: (1) MICT (60 % heart rate reserve, HRR) and (2) HIIT (80 % HRR). MCA velocity, PI, RI, CF, and serum lactate were measured immediately before and after the sessions. HIIT demonstrated improved executive function/semantic fluency (20 %, p = 0.019), while both MICT and HIIT increased lactate (625 %, HIIT, p < 0.001, and 238 %, MICT, p < 0.001). Other assessments remained stable, except for reduced PI (p = 0.029) and RI (p = 0.023) after MICT, with no significant difference (pre-post for HIIT-MICT). Notably, cognition improvement correlated with lactate increase in HIIT (ρ = 0.436; p < 0.001). Executive function/semantic fluency increased after HIIT relative to MICT. The findings show that there are no systematic out-of-normal changes in the cerebrovascular circulation of clinically healthy adults undergoing HIIT and MICT.

Lychnophora ericoides Mart. (Brazilian arnica) ethanol extract accelerates the skin wound healing process: Evidence for its mechanism of action.

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 AT1R 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.

Gallic acid as a Sestrin (SESN2) activator and potential obesity therapeutic agent: A molecular docking study.

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.

Floor Maze Test is capable of differentiating spatial navigation between frail and pre-frail institutionalized older persons.

Investigation of the association between physical frailty and cognitive performance through spatial navigation is important to enable the identification of individuals with cognitive impairment and physical comorbidity. Objective: To analyze the association between spatial navigation and frailty in frail and pre-frail institutionalized older adults. Methods: Forty older people of both sexes, aged 60 years or over, residing in four Brazilian Long-Term Care Facilities (LTCFs) participated in this study. The following tests were applied: Mini-Mental State Examination (MMSE), 2.44m Timed Up and Go, Floor Maze Test (FMT), and Fried's frailty criteria. For data analysis, the Mann-Whitney and independent t-tests were used to compare the groups (frail x pre-frail), principal component analysis was used to explore the main variables related to the data variance, and binary logistic regression to estimate associations. Results: There was a significant difference in performance in the FMT immediate maze time (IMT) (p=0.02) and in the delayed maze time (DMT) (p=0.009) between the pre-frail and frail older adults. An association between FMT DMT performance and frailty was found, showing that older people with shorter times on the DMT (better performance) had approximately four times the chance of not being frail (odds ratio - OR=4.219, 95% confidence interval - 95%CI 1.084-16.426, p=0.038). Conclusion: Frailty is associated with impaired spatial navigation ability in institutionalized older adults, regardless of gait speed performance.

A investigação da associação entre fragilidade física e desempenho cognitivo por meio da navegação espacial é importante para possibilitar a identificação de indivíduos com déficit cognitivo e comorbidade física. Objetivo: Analisar a associação entre navegação espacial e fragilidade em idosos institucionalizados frágeis e pré-frágeis. Métodos: Participaram deste estudo 40 idosos de ambos os sexos, com idade igual ou superior a 60 anos, residentes em quatro instituições de longa permanência (ILPI) brasileiras. Foram aplicados os seguintes testes: Miniexame do Estado Mental (MEEM), 2,44m Timed Up and Go, Floor Maze Test (FMT) e os critérios de fragilidade de Fried. Para a análise dos dados, foram utilizados os testes t independente e de Mann-Whitney para comparar os grupos (frágeis x pré-frágeis), foi feita análise de componentes principais para explorar as principais variáveis relacionadas à variância dos dados e regressão logística binária para estimar associações. Resultados: Houve diferença significativa no desempenho do FMT no tempo imediato do labirinto (TIL) (p=0,02) e no tempo posterior do labirinto (TPL) (p=0,009) entre os idosos pré-frágeis e frágeis. Encontrou-se associação entre o desempenho no FMT TPL e fragilidade, mostrando que idosos com menor tempo de TPL (melhor desempenho) tiveram aproximadamente quatro vezes mais chance de não serem frágeis (odds ratio ­ OR=4,219, intervalo de confiança de 95% ­ IC95% 1,084­16,426, p=0,038). Conclusão: A fragilidade está associada à habilidade de navegação espacial prejudicada em idosos institucionalizados, independentemente do desempenho da velocidade da marcha.

Increased Depression and the Worsening of Depressive Symptoms Associated with Physical Inactivity during the COVID-19 Pandemic: A Two-Phase Cross-Sectional Study.

The COVID-19 pandemic has increased the incidence of depression and other mental disorders in the general population, influenced by various individual and contextual factors. Physical activity (PA) interventions offer a promising approach to mitigating the negative mental health effects of the pandemic. This study aims to analyze the association between PA and depressive symptoms. A total of 785 individuals aged 37.4 ± 13.2 years (72.5% female) were evaluated at two different time points: the first between 2018 and 2019, and the second during the COVID-19 pandemic in 2020. Depressive symptoms, demographic, and socioeconomic data were assessed using the Beck Depression Inventory to estimate depressive symptoms. Frequency analysis and binary and multinomial regression were employed for data analysis. The prevalence of mild depressive symptoms increased from 23.1% before the pandemic to 35.1% during the pandemic. Our findings reveal that practicing PA before the pandemic was a protective factor (OR: 0.19; 95% CI: 0.13, 0.30; p < 0.001) against mild depressive symptoms. Additionally, individuals who continued to practice PA during the pandemic had a lower chance of presenting mild (OR: 0.21; 95% CI: 0.15, 0.30) and moderate/severe (OR: 0.15; 95% CI: 0.08, 0.27) symptoms. Furthermore, our study shows that PA, which was already a protective factor before the pandemic, remained protective during the pandemic, even for those with the highest levels of depression.

Comparative study of dietary fat: lard and sugar as a better obesity and metabolic syndrome mice model.

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.

Identification of potential biomarkers and survival analysis for oral squamous cell carcinoma: A transcriptomic study.

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.

Gallic acid has an inhibitory effect on skin squamous cell carcinoma and acts on the heat shock protein HSP90AB1.

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.

The antineoplastic potential of crotoxin isolated from Crotalus durissus terrificus snake venom on oral squamous cell carcinoma.

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.

Alzheimer's disease genes and proteins associated with resistance and aerobic training: An in silico analysis.

BACKGROUND: Exercise appears to be a viable intervention for maintaining cognitive function and regaining functional autonomy, and perhaps even contributing to a slower progression of Alzheimer's Disease (AD). OBJECTIVE: To explore different neuroplasticity pathways modulated by aerobic and strength training, determine whether signaling pathways overlapped for each specific training method (aerobic and strength training), and evaluate whether there is a functional relationship between APOE and APP gene expression with aerobic training modulated by BDNF; and strength training modulated by IGF-1. METHODS: An in silico analysis was performed to analyze the connection between exercise types and neuroplasticity as a protective factor in AD. The platform provides a protein-protein interaction network translated into known and predicted interactions. A score > 0.70 was determined as high confidence and the network was considered significant when the Protein-Protein Interaction Enrichment was <0.01. RESULTS: Multiple functional associations considered significant between the analyzed proteins. The results of our gene network model support that exercise, both aerobic and strength, can modulate genes that affect hippocampal neuroplasticity and neurogenesis, which may delay cognitive decline and Alzheimer's related symptoms. CONCLUSION: The investigation about the functional association of aerobic training via BDNF in the modulation of APP, APOE, and MAPT genes in the hippocampus seems to be established, while strength training seems to induce the production of IGF-1 and IGF-1R, modulating AKT1.

Effect of low-level light therapy before radiotherapy in oral squamous cell carcinoma: An in vitro study.

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/cm2) 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/cm2 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.

Comparison between two antimicrobial photodynamic therapy protocols for oral candidiasis in patients undergoing treatment for head and neck cancer: A two-arm, single-blind clinical trial.

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.

Photodynamic therapy mediated by nanoparticles Aluminum Chloro Phthalocyanine in oral squamous carcinoma cells.

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/cm2 irradiation), Group 3 (AlPc-NE alone), and Group 4 (AlPc-NE + 28.3 J/cm2 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.

Development and Evaluation of a Low-cost Dairy Food Supplement with Mauritia Flexuosa (Buriti) to Combat Malnutrition: Translational Study in Mice and Institutionalized Elderly Woman.

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.

Neutrophil extracellular traps (NETs) modulate inflammatory profile in obese humans and mice: adipose tissue role on NETs levels.

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.

The Link between Exercise and Homocysteine in the Alzheimer's Disease: A Bioinformatic Network Model.

Elevated peripheral expression of homocysteine (Hcy) is associated with an increased risk of coronary heart disease and stroke, diabetes, and cancer. It is also associated with cognitive impairment as it has been reported that high levels of Hcy cause cognitive dysfunction and memory deficit. Among several etiological factors that contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Hcy seems to directly contribute to the generation of neurotoxicity factors. This study aims to hypothesize the molecular mechanism by which exercise can reduce the risk of neurological complications promoted by hyperhomocysteinemia (HHcy), and discuss how exercise could reduce the risk of developing AD by using bioinformatics network models. According to the genes network, there are connections between proteins and amino acids associated with Hcy, exercise, and AD. Studies have evidenced that exercise may be one of several processes by which acid nitric availability can be maximized in the human body, which is particularly important in reducing cell loss and tau pathology and, thereby, leading to a reduced risk of complications associated with HHcy and AD.

The combination of traditional and auricular acupuncture to prevent xerostomia and anxiety in irradiated patients with HNSCC: a preventive, parallel, single-blind, 2-arm controlled study.

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.