RESUMO
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.
Assuntos
Carcinoma de Células Escamosas , Metformina , Neoplasias Bucais , Radiossensibilizantes , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Neoplasias Bucais/radioterapia , Radiossensibilizantes/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Tolerância a Radiação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Gliceraldeído-3-Fosfato Desidrogenases , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora) , Hipóxia Celular/efeitos dos fármacos , Hipóxia Tumoral/efeitos dos fármacosRESUMO
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.
Assuntos
Neoplasias de Cabeça e Pescoço , Sarcopenia , Humanos , Idoso , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Transversais , Proteína C-Reativa , Neoplasias de Cabeça e Pescoço/complicaçõesRESUMO
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.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Transcriptoma , Neoplasias Bucais/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise de Sobrevida , Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/genética , PrognósticoRESUMO
Hibiscus sabdariffa L. is a worldwide component for tea and beverages, being a natural source of anthocyanins, which are associated with cardiovascular activities. To investigate this relationship, we explored different methods of aqueous extraction on the anthocyanin content and antioxidant activity of H. sabdariffa L. calyx extract (HSCE). Pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotide levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239, and on the vasomotor response of aortic rings isolated from mice are studied herewith. We found that the application of ultrasonic turbolization, 20 min, combined with acidified water was significantly more effective in the extraction process, providing extracts with the highest levels of anthocyanins (8.73 and 9.63 mg/100 g) and higher antioxidant activity (6.66 and 6.78 µM trolox/g of sample). HSCE significantly inhibited (100-1000 µg/mL) arachidonic acid-induced platelet aggregation, reduced calcium mobilization, and increased cAMP and cGMP levels with VASPSer157 and VASPSer239 phosphorylation. Vasorelaxation reduction was confirmed by the aortic rings and endothelium assays treated with nitric oxide synthase inhibitors, soluble guanylyl cyclase (sGC) oxidizing agent, or Ca2+-activated K+ channel inhibitor. The increasing of cGMP levels could be understood considering the sGC stimulation by HSCE compounds in the specific stimulus domain, which allows an understanding of the observed antiplatelet and vasorelaxant properties of H. sabdariffa L. calyx extract.
Assuntos
Hibiscus , Vasodilatadores , Animais , Camundongos , Vasodilatadores/farmacologia , Antocianinas/farmacologia , Antioxidantes/farmacologia , Cálcio , Extratos Vegetais/farmacologia , GMP Cíclico/metabolismoRESUMO
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.
Assuntos
Armadilhas Extracelulares , Tecido Adiposo/metabolismo , Animais , Armadilhas Extracelulares/metabolismo , Humanos , Inflamação/metabolismo , Camundongos , Neutrófilos/metabolismo , Obesidade/metabolismoRESUMO
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.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Nanopartículas , Compostos Organometálicos , Fotoquimioterapia , Alumínio , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Isoindóis , Antígeno Ki-67 , Neoplasias Bucais/tratamento farmacológico , Compostos Organometálicos/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
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 (nâ¯=â¯8): standard diet (ST), standard diet plus Enalapril (STâ¯+â¯ENAL), hyperlipidic diet (HF) and hyperlipidic diet plus Enalapril (HFâ¯+â¯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.
Assuntos
Dieta Hiperlipídica , Enalapril , Fígado , Peptidil Dipeptidase A , Animais , Glicemia/metabolismo , Resistência à Insulina , Masculino , Camundongos , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
Neutrophil extracellular traps (NETs) represent an innate organism defense mechanism characterized by neutrophil release of intracellular material to capture any aggressor agent. Elevated NETs release is associated with increased inflammatory response and related diseases, such as obesity. Chronic physical training is one of the main strategies to treat and prevent obesity. The relationship between physical training and NETs is still under study. The present review, followed by a bioinformatics analysis, demonstrates the meaningful connection between physical exercise, obesity, and NETs. The bioinformatics indicated TNF-α as a leading gene after the ontological analysis followed by positive-interleukin-6 regulation, chemokines, and inflammatory response regulation. The main results pointed to a relevant regulatory effect of physical training on NETs release, indicating physical exercise as a possible therapeutic target on modulating NETs and inflammation.
Assuntos
Exercício Físico/genética , Inflamação/genética , Obesidade/genética , Fator de Necrose Tumoral alfa/genética , Biologia Computacional , Armadilhas Extracelulares/genética , Humanos , Inflamação/fisiopatologia , Inflamação/terapia , Neutrófilos/metabolismo , Obesidade/fisiopatologia , Obesidade/terapiaRESUMO
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.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Lactococcus lactis/metabolismo , Fígado/efeitos dos fármacos , Probióticos/farmacologia , Resveratrol/farmacologia , Administração Oral , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Colesterol/sangue , Biologia Computacional , Feminino , Regulação da Expressão Gênica/genética , Ontologia Genética , Imuno-Histoquímica , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol/administração & dosagem , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas Priônicas , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Neoplasias de Cabeça e Pescoço/genética , Humanos , Proteínas Priônicas/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
Despite all the development of modern medicine, around 100 compounds derived from natural products were undergoing clinical trials only at the end of 2013. Among these natural substances in clinical trials, we found the resveratrol (RES), a pharmacological multi-target drug. RES analgesic properties have been demonstrated, although the bases of these mechanisms have not been fully elucidated. The aim of this study was to evaluate the involvement of opioid and cannabinoid systems in RES-induced peripheral antinociception. Paw withdrawal method was used and hyperalgesia was induced by carrageenan (200⯵g/paw). All drugs were given by intraplantar injection in male Swiss mice (nâ¯=â¯5). RES (100⯵g/paw) administered in the right hind paw induced local antinociception that was antagonized by naloxone, non-selective opioid receptor antagonist, and clocinnamox, µOR selective antagonist. Naltrindole and nor-binaltorfimine, selective antagonists for δOR and kOR, respectively, did not reverse RES-induced peripheral antinociception. CB1R antagonist AM251, but not CB2R antagonist AM630, antagonized RES-induced peripheral antinociception. Peripheral antinociception of RES intermediate-dose (50⯵g/paw) was increased by: (i) bestatin, inhibitor of endogenous opioid degradation involved-enzymes; (ii) MAFP, inhibitor of anandamide amidase; (iii) JZL184, inhibitor of 2-arachidonoylglycerol degradation involved-enzyme; (iv) VDM11, endocannabinoid reuptake inhibitor. Acute and peripheral administration of RES failed to affect the amount of µOR, CB1R and CB2R. Experimental data suggest that RES induces peripheral antinociception through µOR and CB1R activation by endogenous opioid and endocannabinoid releasing.
Assuntos
Analgésicos/farmacologia , Endocanabinoides/metabolismo , Hiperalgesia/prevenção & controle , Dor Nociceptiva/prevenção & controle , Peptídeos Opioides/metabolismo , Receptor CB1 de Canabinoide/agonistas , Receptores Opioides mu/agonistas , Resveratrol/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Antagonistas de Receptores de Canabinoides/farmacologia , Carragenina , Modelos Animais de Doenças , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Hiperalgesia/psicologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/metabolismo , Dor Nociceptiva/psicologia , Receptor CB1 de Canabinoide/metabolismo , Receptores Opioides mu/metabolismo , Transdução de SinaisRESUMO
PURPOSE: Leptin, an important hormone controlling energy homeostasis, has been linked to the pathogenesis of oral squamous cell carcinoma (OSCC). Evidence indicates that head and neck cancer patients undergoing radiotherapy show decreased leptin levels after radiotherapy treatment. Thus, we investigated, through phenotypic and molecular analyses, whether leptin can compromise the therapeutic effect of ionizing radiation and neoplastic behavior of OSCC cells. METHODS: The human OSCC-derived cell lines SCC9 and SCC4 were treated with human recombinant leptin and exposed to 6 Gy of irradiation. We performed the in vitro assays of cell migration, death, proliferation, and colony-forming ability. The reactive oxygen species (ROS) levels and proteome analysis by mass spectrometry were also conducted. RESULTS: Leptin was able to increase cell proliferation, migration, and colony-forming ability, despite the suppressive effect induced by irradiation. Furthermore, the leptin promoted a significant reduction of ROS intracellular accumulation, and increased expression of the cancer-related proteins, as ACTC1, KRT6A, and EEF2 in irradiated OSCC cells. CONCLUSIONS: Our findings suggest that leptin impairs responsivity of OSCC cells to the ionizing radiation, reducing the suppressive effects of irradiation on the neoplastic phenotype, and increasing protein expression critical to carcinogenesis.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Leptina/efeitos adversos , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Radiação Ionizante , Actinas/genética , Actinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Humanos , Queratina-6/genética , Queratina-6/metabolismo , Leptina/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais CultivadasRESUMO
OBJECTIVE: Malignant salivary gland tumors (MSGTs) present different phenotypic characteristics and various clinical outcomes, which proved to be a diagnostic challenge. Considering the heterogeneity of MSGT, this study aims to identify molecule related to the nature of MSGT. METHODS: For screening, proteomic analysis comparing MSGT with pleomorphic adenoma (PA) and salivary gland was performed. The MSGT-associated protein which presented in the higher number in the Gene Expression Omnibus (GEO) database was selected. To validate the data, immunohistochemistry (IHC) was performed in 14 patients with PA, 22 patients with MSGT, and 14 controls. RESULTS: 16 proteins were associated with MSGT. ANXA2 was the primary protein, according to GEO database analyses. ANXA2 was most expressed in the cell membrane. However, some ANXA2 staining was also observed in the cytoplasm and nucleus. ANXA2 was highly expressed in MSGT in comparison with control. Also, ANXA2 has a higher expression in adenocarcinoma not otherwise specified (ANOS) and myoepithelial carcinoma (MC) in comparison with PA. CONCLUSION: In conclusion, this study demonstrated that MSGT presented higher levels of ANXA2 in comparison with normal salivary glands. Also, ANXA2 might be interesting as a molecular marker of ANOS and MS.
Assuntos
Adenoma Pleomorfo/metabolismo , Anexina A2/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Adenoma Pleomorfo/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoide Cístico/patologia , Carcinoma Mucoepidermoide/patologia , Estudos de Casos e Controles , Humanos , Proteoma , Proteômica , Neoplasias das Glândulas Salivares/patologiaRESUMO
Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the most common adverse effects of OSCC treatment. Currently, there is no consensus for OM treatment. The purpose of the current study was to test the combination of red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture of human fibroblast was performed to identify LLLT dose. After laboratory tests, a two-arm parallel, single-blind, controlled study was conducted. The two arms were group 1, both 660- and 808-nm wavelengths (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2), and group 2, only 660-nm wavelength (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2). Both treatments were performed twice a week. Group 1 presented a reduction of mucositis grade in comparison to group 2. Group 1 also presented reduction of analgesics prescription. But no significant differences between groups 1 and 2 were observed according to the pain scale. In conclusion, the current study demonstrated that a combination of red and infrared at a higher dose (300 J/cm2) reduced both oral mucositis grade and analgesics prescription. The effects of the combination of RT and LLLT are unclear and need more studies.
Assuntos
Analgésicos/uso terapêutico , Terapia com Luz de Baixa Intensidade , Dor/radioterapia , Estomatite/tratamento farmacológico , Estomatite/radioterapia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibroblastos/patologia , Fibroblastos/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Método Simples-CegoRESUMO
A bioreactor was built by means of immobilizing alpha-amylase from Aspergillus oryzae by encapsulation, through cryopolymerization of acrylamide monomers for the continuous starch hydrolysis. The starch hydrolysis was evaluated regarding pH, the concentration of immobilized amylase on cryogel, the concentration of starch solution and temperature. The maximum value for starch hydrolysis was achieved at pH 5.0, concentration of immobilized enzyme 111.44 mg amylase /gcryogel , concentration of starch solution 45 g/L and temperature of 35°C. The immobilized enzyme showed a conversion ratio ranging from 68.2 to 97.37%, depending on the pH and temperature employed. Thus, our results suggest that the alpha-amylase from A. oryzae immobilized on cryogel monoliths represents a potential process for industrial production of maltose from starch hydrolysis.
Assuntos
Reatores Biológicos , Criogéis/química , Enzimas Imobilizadas/metabolismo , Amido/metabolismo , alfa-Amilases/metabolismo , Aspergillus oryzae , Enzimas Imobilizadas/química , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Maltose/metabolismo , Porosidade , Amido/análise , Amido/química , Temperatura , alfa-Amilases/químicaRESUMO
BACKGROUND: Understanding the biological processes underlying Pressure Ulcer (PU) is an important strategy to identify new molecular targets. Bioinformatics has emerged as an important screening tool for a broad range of diseases. OBJECTIVE: This study aim of the current study is to investigate the protein-protein interaction in the PU context by bioinformatics. METHODS: We performed a search in gene databases, and bioinformatics algorithms were used to generate molecular targets for PU based in silico investigation. Interactions networks between protein-coding genes were built and compared to skin. RESULTS: TNFA, MMP9, and IL10 genes have higher disease-related connectivity than a connectivity general global. MAGOH, UBC, and PTCH1 as were leader genes related to skin. Ontological analysis demonstrated different mechanisms associated, such as response to oxidase stress. CONCLUSION: TNFA, MMP9, and IL10 are possible therapeutic targets for pressure ulcer. Additional investigation of cell post-transcriptional machinery should be investigated in PU.
Assuntos
Biologia Computacional/métodos , Expressão Gênica , Úlcera por Pressão/genética , Algoritmos , HumanosRESUMO
Recent studies show that skipping breakfast is associated with an increased risk of obesity, diabetes and cardiovascular diseases. In this context, this study evaluated 400 patients from the Brazilian health service who had their nutritional status defined based on the body mass index and were classified as physically active or insufficient active. The energy intake and macronutrients was also assessed by a 24-hour dietary recall where the association of overweight/obesity with the investigated variables was evaluated using chi-square, Student's t test and multivariate analysis (p < 0.05). The main results showed that more than half of the studied population have the habit of omitting breakfast (55.8%), and among those, 81.2% were overweight/obese (p < 0.0001). Almost three-fourths of these individuals consumed no more than 4 meals a day (73.0%), and regarding this meal frequency/day, 78.8% of the individuals who reported having 4 meals or less a day were overweight/obese compared with 57.8% who reported as having 5-6 meals/day (p < 0.0001). The individuals who reported to omit breakfast had a higher chance of being overweight compared with those who had this habit (OR 2.20; 95% CI 1.40-3.60) and the chance of the physically insufficient active individuals to be overweight/obese was 2.9 times higher when compared to the active individuals (p < 0.0001). Our findings suggest that regular breakfast consumption may decrease overweight and obesity risk.
Assuntos
Desjejum , Ingestão de Energia , Exercício Físico , Comportamento Alimentar , Estado Nutricional , Obesidade/fisiopatologia , Adulto , Índice de Massa Corporal , Brasil , Desjejum/fisiologia , Ritmo Circadiano , Estudos Transversais , Comportamento Alimentar/fisiologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: Adipose tissue is central to the regulation of energy balance. Two functionally different fat pads are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue (BAT), which is specialized in heat production. In this context, new strategies capable of modulating the development and function of white and BAT become relevant. In the present study, we analyzed the influence of resveratrol (sirtuin activator) on energy balance and the expression of thermogenesis markers. METHODS: Mice were divided into two groups: standard diet (ST) and standard diet plus resveratrol (ST + RSV). RESULTS: After 2 months of treatment, ST + RSV mice presented significantly decreased fat accumulation in adipose tissue, with diminished total cholesterol and glucose plasma levels. Additionally, increased oxygen consumption was observed in ST + RSV group. Analyses of mRNA of thermogenesis-related genes showed significant increase in UCP1, SIRT1, PTEN and BMP-7 expression in BAT. CONCLUSION: Our data suggest that improved metabolism produced by oral administration of resveratrol is, at least in part, associated with increased thermogenesis followed by high expression of UCP1 and SIRT1, which can mediate higher energy expenditure and decreased fat accumulation in adipose tissue.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/metabolismo , Dieta , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Camundongos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Resveratrol , Sirtuína 1/genética , Proteína Desacopladora 1RESUMO
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.
RESUMO
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.