RESUMO
Mesenchymal stromal cells (MSCs) have therapeutic potential due to their abilities of differentiation, immunomodulation, and migration to injured tissues, potentiating such effects when cells are activated. Guarana (Paullinia cupana) is a tropical plant species found in South America that is known for its antioxidant, stimulant, and cicatricial effects. The guarana extract is composed of many substances and caffeine is the main component. The objective was to evaluate the effects of guarana and caffeine on MSCs. After the initial characterization, MSCs were treated with Paullinia cupana (10, 100, and 1000 µg/mL) or caffeine (0.4, 4, and 40 µg/mL) for 24 h. MSCs treatment with 1000 µg/mL guarana increased cell polarity, viability, cell migration to chemoattractant, antioxidant potential, and liberation of extracellular vesicles (EVs), while it reduced the levels of autophagy. MSCs treated with 100 and 1000 µg/mL guarana or 40 µg/mL caffeine showed a decrease of cell proliferation. No treatment affected the cellular area and cell cycle of MSCs. The study shows in vitro evidence that guarana could be a promising alternative for activating MSCs to promote better cellular products for future clinical therapies.
Assuntos
Proliferação de Células , Células-Tronco Mesenquimais , Paullinia , Extratos Vegetais , Medicina Regenerativa , Paullinia/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Extratos Vegetais/farmacologia , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cafeína/farmacologia , Células Cultivadas , Diferenciação Celular/efeitos dos fármacos , Antioxidantes/farmacologia , Humanos , AnimaisRESUMO
BACKGROUND/OBJECTIVES: Obesity is a metabolic disorder that predisposes patients to numerous diseases and has become a major global public-health concern. Animal models of diet-induced obesity (DIO) are frequently used to study obesity, but which DIO model most accurately reflects the pathology of human obesity remains unclear. In this study, we designed a diet based on the human Western diet (WD) and compared it with the cafeteria diet (CAF) and high-fat diet (HFD) in order to evaluate which diet most closely mirrors human obesity. METHODS: Wistar rats were fed four different diets (WD, CAF, HFD and a low-fat diet) for 18 weeks. Metabolic parameters and gut microbiota changes were then characterized. RESULTS: Rats fed the four different diets exhibited completely different phenotypes, highlighting the importance of diet selection. This study also revealed that WD most effectively induced obesity and obesity-related disorders, and thus proved to be a robust model of human obesity. Moreover, WD-fed rats developed obesity and obesity-related comorbidities independent of major alterations in gut microbiota composition (dysbiosis), whereas CAF-fed rats developed the greatest dysbiosis independent of obesity. We also characterized gut microbiota after feeding on these four different diets and identified five genera that might be involved in the pathogenesis of obesity. CONCLUSIONS: These data suggest that diet, and not the obese state, was the major driving force behind gut microbiota changes. Moreover, the marked dysbiosis observed in CAF-fed rats might have resulted from the presence of several additives present in the CAF diet, or even a lack of essential vitamins and minerals. Based on our findings, we recommend the use of the prototypic WD (designed here) in DIO models. Conversely, CAF could be used to investigate the effects of excessive consumption of industrially produced and highly processed foods, which are characteristic of Western society.
Assuntos
Dieta Ocidental , Microbioma Gastrointestinal/fisiologia , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Obesidade/microbiologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Disbiose/metabolismo , Fast Foods , Masculino , Obesidade/fisiopatologia , Ratos , Ratos WistarRESUMO
Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-ß precursor protein-α has been shown to be elevated in severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria-related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg(2+)) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.
Assuntos
Doença de Alzheimer/genética , Transtorno Autístico/genética , Cerebelo/metabolismo , Conectoma , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Apoptose/genética , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/patologia , Transtorno Autístico/fisiopatologia , Cerebelo/efeitos dos fármacos , Cerebelo/patologia , Cerebelo/fisiopatologia , Simulação por Computador , Bases de Dados Genéticas , Desenho de Fármacos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Terapia de Alvo Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Prognóstico , Transdução de Sinais/genética , Biologia de Sistemas , Transcrição GênicaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is recognized world-wide as an aggressive disease with poor prognosis in patients with or without resection. Further knowledge about the biological mechanisms of PDAC is necessary to enable the identification of novel molecular markers and therapeutic targets for early diagnosis and improved treatment. Transcription factors are the final effectors of signaling pathways and regulate a number of cellular functions. Changes in their expression may contribute to cellular transformation and tumor progression. Thus, the aim of the present study was to identify the Master Regulators (MRs) of transcription potentially involved in PDAC disease. To achieve this goal, we utilized microarray data to correlate MR genes with the tumor phenotype. Analyses were performed with RTN, Limma, and Survival packages in the R environment. We identified Tubby-like protein 3 (TULP3) as a MR of transcription in PDAC samples. The prognostic value of TULP3 was assessed in three independent cohort analyses. Our data demonstrated that pancreatic cancer patients exhibiting high transcriptional levels of TULP3 showed a poor overall survival rate. High expression levels of TULP3 may play an essential role in pancreatic cancer progression and possibly lead to a poor clinical outcome. Our results highlight the potential use of TULP3 as a clinical prognostic biomarker for pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/patologia , Biologia Computacional/métodos , Proteínas/genética , Adenocarcinoma/genética , Algoritmos , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Bases de Dados Genéticas , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Análise em Microsséries/métodos , Análise de SobrevidaRESUMO
Challenging of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharides (LPS) has been shown to activate monocytes and macrophages, leading to the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Manganese superoxide dismutase (MnSOD) is an important enzyme that may play a central role in the response to oxidative stress. 47C> T SNP of the SOD2 gene, the -9Val MnSOD is less efficient than the -9Ala version. We have previously characterized the cellular redox status of human PBMCs expressing either -9Ala (CC) or -9Val (TT) SOD2 and analyzed the responses of these cells to oxidative stress induced by LPS. Due to the observed alterations in the activities of these antioxidant enzymes, we decided to investigate their immunocontent and analyze the production of intracellular oxidants, as well as any resulting DNA damage. PBMCs were isolated from the blood of 30 healthy human volunteers (15 volunteers per allele). We then analyzed levels of nitrite, DNA damage by comet assay, TNF-α, carboxymethyl lysine and nitrotyrosine and assessed production of intracellular reactive species by the DCFH-DA-based assay and western blots were used to analyze protein levels. Our results show that there occurs an increase in nitric oxide production in both allele groups after challenge with LPS. A significant increase in DNA damage was observed in PBMCs after an 8-h LPS challenge. Cells expressing the SOD2 47C allele quickly adapt to a more intense metabolism by upregulating cellular detoxification mechanisms. However, when these cells are stressed over a long period, they accumulate a large quantity of toxic metabolic byproducts.
Assuntos
Leucócitos Mononucleares/enzimologia , Lipopolissacarídeos/farmacologia , Polimorfismo de Nucleotídeo Único , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Adulto , Células Cultivadas , Dano ao DNA , Estudos de Associação Genética , Humanos , Cinética , Leucócitos Mononucleares/imunologia , Masculino , Mitocôndrias/metabolismo , Nitritos/metabolismo , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Adulto JovemRESUMO
3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a disorder biochemically characterized by the predominant accumulation of 3-hydroxy-3-methylglutarate (HMG), 3-methylglutarate (MGA), 3-methylglutaconate and 3-hydroxyisovalerate in tissues and biological fluids of the affected patients. Neurological symptoms and hepatopathy are commonly found in HL deficiency, especially during metabolic crises. Since the mechanisms of tissue damage in this disorder are not well understood, in the present study we evaluated the ex vivo effects of acute administration of HMG and MGA on important parameters of oxidative stress in cerebral cortex and liver from young rats. In vivo administration of HMG and MGA provoked an increase of carbonyl and carboxy-methyl-lysine formation in cerebral cortex, but not in liver, indicating that these metabolites induce protein oxidative damage in the brain. We also verified that HMG and MGA significantly decreased glutathione concentrations in both cerebral cortex and liver, implying a reduction of antioxidant defenses. Furthermore, HMG and MGA increased 2',7'-dichlorofluorescin oxidation, but did not alter nitrate and nitrite content in cerebral cortex and liver, indicating that HMG and MGA effects are mainly mediated by reactive oxygen species. HMG and MGA also increased the activities of superoxide dismutase and catalase in cerebral cortex and liver, whereas MGA decreased glutathione peroxidase activity in cerebral cortex. Our present data showing a disruption of redox homeostasis in cerebral cortex and liver caused by in vivo administration of HMG and MGA suggest that this pathomechanism may possibly contribute to the brain and liver abnormalities observed in HL-deficient patients.
Assuntos
Acetil-CoA C-Acetiltransferase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Antioxidantes/metabolismo , Córtex Cerebral/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Acetil-CoA C-Acetiltransferase/metabolismo , Animais , Córtex Cerebral/enzimologia , Córtex Cerebral/metabolismo , Homeostase , Fígado/enzimologia , Fígado/metabolismo , Oxirredução , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
This study aimed to evaluate whether natural or synthetic steroid hormones could directly modulate the activity of the different superoxide dismutase (SOD) isoforms found in human blood fractions without changing enzyme expression. Enzyme samples of human erythrocytes, the human platelet-rich plasma fraction (PRP) or isolated CuZnSOD, which was purified from human erythrocytes were pre-incubated with natural steroids (17ß-estradiol 17-acetate and progesterone) and their synthetic derivatives (ß-estradiol 3-benzoate and medroxyprogesterone 17-acetate). Then, CuZn and MnSOD activities were measured using the xanthine/xanthine oxidase/nitroblue tetrazolium method. Hormones had no effect on MnSOD activity from the PRP, but we show for the first time that natural and synthetic steroid hormones have a direct, bell-shaped effect on the activity of CuZnSOD from both male and female human erythrocytes. Low (physiological) hormone concentrations caused a dose-dependent increase in enzyme activity, which disappeared at higher hormone concentrations. In addition, the combination of synthetic and natural estrogens and progestins had a synergistic stimulatory effect on the activity of CuZnSOD from human erythrocytes. The molecular interaction between CuZnSOD and steroid hormones was preliminarily studied. Natural hormones did not change the electrophoretic mobility of SOD under denaturing conditions, but they did increase the absorption spectra of SOD in the 230-290 nm range. These data suggest that hormone-mediated modulation of CuZnSOD is related to subtle changes in protein conformation, possibly related to Trp and Phe residues. We propose that this effect may account for the physiological regulation of enzyme activity during conditions where steroid hormones undergo alterations as the ovulatory cycle.
Assuntos
Eritrócitos/enzimologia , Estradiol/análogos & derivados , Acetato de Medroxiprogesterona/farmacologia , Superóxido Dismutase/sangue , Adulto , Ensaios Enzimáticos , Eritrócitos/efeitos dos fármacos , Estradiol/química , Estradiol/farmacologia , Estradiol/fisiologia , Feminino , Humanos , Isoenzimas/sangue , Isoenzimas/química , Masculino , Acetato de Medroxiprogesterona/química , Progesterona/química , Progesterona/farmacologia , Progesterona/fisiologia , Ligação Proteica , Superóxido Dismutase/química , Superóxido Dismutase-1 , Adulto JovemRESUMO
The redox properties of the hydroethanol extract (EE) and its ethyl acetate (EAF) and hydromethanol (HMF) fractions obtained from Abarema cochliacarpos (Gomes) Barneby & Grimes stem bark were evaluated. EAF had the highest total phenol content (848.62 ± 78.18 mg g⻹), while EE showed the highest content of catechin (71.2 µg g⻹). EE, EAF and HMF exhibited the highest levels of antioxidant activity at 100 and 1000 µg mL⻹ when the non-enzymatic antioxidant potential was evaluated by the total reactive antioxidant potential, total antioxidant reactivity and nitric oxide scavenging assays. In addition, EAF and HMF showed SOD-like activity. The results for EE, EAF and HMF in this study showed that A. cochliacarpos (Gomes) Barneby & Grimes stem bark have redox properties and may be able to help the endogenous enzymatic and non-enzymatic systems to keep the redox balance.
Assuntos
Fabaceae/química , Casca de Planta/química , Extratos Vegetais/química , Caules de Planta/química , Antioxidantes/química , OxirreduçãoRESUMO
OBJECTIVE: To investigate the relationship between antioxidant biomarkers and food intake in elderly women. DESIGN: Cross-sectional study. SETTING: Recreation Center for the Elderly in the city of Itajaí, Santa Catarina, Brazil. PARTICIPANTS: 73 elderly women with an average age of 71 years, 93% caucasian, average body weight 68.7 ± 13.1 kg and average BMI 28.5 ± 2.3 kg/m². MEASUREMENTS: Nutritional status was assessed based on the Body Mass Index (BMI). Data on food intake were obtained by applying the 24h diet recall method in three non-consecutive days, including Sunday. The assessment of antioxidant biomarkers was performed based on tests for total plasma thiols and phenolic compounds. The linear regression analysis was used to assess the effect of the consumption of food groups on antioxidant biomarkers. RESULTS: A positive association was found between thiols and intake of carotenoid-rich vegetables (p=0.03), oils, fats and oilseeds (p=0.03); a negative association was observed between total concentrations of phenolic compounds and intake of cereals (p=0.04). CONCLUSION: The intake of foods from the carotenoid-rich vegetables, oils, fats and oilseeds food groups increased the levels of plasma thiols, and the intake of foods from the group of cereals decreased the plasma concentration of phenols. Studies should be conducted to investigate the association between the intake of antioxidant-rich foods and the plasma antioxidant profile, as a way to protect against the aging process.
Assuntos
Antioxidantes/metabolismo , Carotenoides/farmacologia , Dieta , Gorduras na Dieta/farmacologia , Grão Comestível/efeitos adversos , Estado Nutricional , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Brasil , Dieta/efeitos adversos , Ingestão de Energia , Feminino , Avaliação Geriátrica , Humanos , Modelos Lineares , Avaliação Nutricional , Fenóis/sangue , Compostos de Sulfidrila/sangueRESUMO
Ethanol (EtOH) is a drug widely consumed throughout the world that promotes several neurochemical disorders. Its deleterious effects are generally associated with modifications in oxidative stress parameters, signaling transduction pathways, and neurotransmitter systems, leading to distinct behavioral changes. Taurine (2-aminoethanesulfonic acid) is a ß-amino acid not incorporated into proteins found in mM range in the central nervous system (CNS). The actions of taurine as an inhibitory neurotransmitter, neuromodulator, and antioxidant make it attractive for studying a potential protective role against EtOH-mediated neurotoxicity. In this study, we investigated whether acute taurine cotreatment or pretreatment (1 h) prevent EtOH-induced changes in acetylcholinesterase (AChE) activity and in oxidative stress parameters in zebrafish brain. The results showed that EtOH exposure (1% in volume) during 1 h increased AChE activity, whereas the cotreatment with 400 mg·L(-1) taurine prevented this enhancement. A similar protective effect of 150 and 400 mg·L(-1) taurine was also observed when the animals were pretreated with this amino acid. Taurine treatments also prevented the alterations promoted in superoxide dismutase and catalase activities by EtOH, suggesting a modulatory role in enzymatic antioxidant defenses. The pretreatment with 150 and 400 mg·L(-1) taurine significantly increased the sulfydryl levels as compared to control and EtOH groups. Moreover, 150 and 400 mg·L(-1) taurine significantly decreased thiobarbituric acid reactive species (TBARS) levels, but the cotreatment with EtOH plus 400 mg·L(-1) taurine did not prevent the EtOH-induced lipoperoxidation. In contrast, the pretreatment with 150 and 400 mg·L(-1) taurine prevented the TBARS increase besides decreased the basal levels of lipid peroxides. Altogether, our data showed for the first time that EtOH induced oxidative stress in adult zebrafish brain and reinforce the idea that this vertebrate is an attractive alternative model to evaluate the beneficial effect of taurine against acute EtOH exposure.
Assuntos
Acetilcolinesterase/efeitos dos fármacos , Transtornos do Sistema Nervoso Induzidos por Álcool/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Taurina/farmacologia , Acetilcolinesterase/metabolismo , Transtornos do Sistema Nervoso Induzidos por Álcool/enzimologia , Transtornos do Sistema Nervoso Induzidos por Álcool/metabolismo , Animais , Encéfalo/enzimologia , Encéfalo/metabolismo , Inibidores da Colinesterase/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Fármacos Neuroprotetores/metabolismo , Estresse Oxidativo/fisiologia , Especificidade da Espécie , Taurina/metabolismo , Peixe-ZebraRESUMO
The aim of this study was to evaluate the effects of acute alcohol consumption and vitamin E co-treatment upon oxidative stress parameters in rats tongue. Thirty-eight, Wistar rats were separated into five groups (alcohol, alcohol/vitamin E, control, Tween, vitamin E). Alcohol and alcohol vitamin E groups had the standard diet, and 40% alcohol on drinking water. Other groups were fed with the same standard diet and water ad libitum. Vitamin E was given by gavage to vitamin E and alcohol/vitamin E rats twice a week. Alcohol and control groups were subjected to saline gavage and Tween group to 5% Tween 80 solution, the vitamin E vehicle. At day 14, the animals were anesthetized and specimens were obtained from tongue. Lipid peroxidation (TBARS), protein oxidative damage, catalase (CAT) and superoxide dismutase (SOD) activities were quantified. Alcohol group decreased TBARS in relation to control group and alcohol vitamin-treated animals decreased TBARS when compared to Tween and vitamin E groups. SOD activity was lower and CAT activity was higher in animals treated with both alcohol and vitamin E. These results suggest that short-term alcohol consumption decreases lipid peroxidation levels. Alternatively, alcohol/vitamin E group increased CAT, showing the toxicity of this association.
Assuntos
Antioxidantes/farmacologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Língua/metabolismo , Vitamina E/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição , Tamanho do Órgão/efeitos dos fármacos , Polissorbatos/farmacologia , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Tensoativos/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Língua/efeitos dos fármacos , Língua/enzimologiaRESUMO
Ovarian sizes (length and width) were measured in young females of Anastrepha fraterculus (Wiedemann) (Diptera, Tephritidae) subjected or not to the inhibitor alpha-difluormethylornithine (alpha-DFMO). The most effective concentration of alpha-DMFO used was 50 mM and the ovarian measurements (length and width) of the treated females were smaller than those of females not treated with alpha-DMFO. These data may suggest some relationship between ornithine decarboxylase (ODC) and sexual maturation in A. fraterculus.
Assuntos
Eflornitina/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores da Ornitina Descarboxilase , Ovário/efeitos dos fármacos , Tephritidae/efeitos dos fármacos , Animais , Feminino , Tamanho do Órgão/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Tephritidae/anatomia & histologia , Tephritidae/enzimologiaRESUMO
Glycolaldehyde (GA) is a highly reactive aldehyde that can be generated during inflammation and hyperglycemia. It can react with arginine and lysine residues impairing protein function. As inflammation and diabetes present haemostatic dysfunction, we hypothesized that GA could participate in this process. The aim of this study was to investigate if plasma incubated in the presence of GA presents alteration in the coagulation process. We also aimed to evaluate the role of fibrinogen in GA-induced haemostatic dysfunction. For this purpose, plasma and fibrinogen were each incubated separately, either in the presence or absence of 1 mM GA for 8 and 4 h, respectively. After that, plasma coagulation and fibrin polymerization kinetics were recorded, as well as the kinetic of plasma clot digestion and fibrinolysis protein carbonylation was quantified. An SDS-PAGE was run to check the presence of cross-linking between fibrinogen chains. GA induced a delay in plasma coagulation and in fibrin polymerization. Maximum absorbance decreased after GA treatment, indicating the generation of thinner fibers. Fibrin generated after complete coagulation showed resistance to enzymatic digestion, which could be related to the generation of thinner fibers. Protein carbonylation also increased after GA treatment. All parameters could be reversed with AMG (a carbonyl trap) co-treatment. The data presented herein indicate that GA causes post-translational modification of lysine and arginine residues, which are central to many events involving fibrinogen to fibrin conversion, as well as to fibrinolysis. These modifications lead to the generation of persistent clots and may contribute to mortality seen in pathologies such diabetes and sepsis.
Assuntos
Acetaldeído/análogos & derivados , Coagulação Sanguínea/efeitos dos fármacos , Fibrinogênio/química , Tripsina/química , Acetaldeído/química , Acetaldeído/farmacologia , Fibrinogênio/metabolismo , Fibrinólise , Cinética , Carbonilação Proteica/efeitos dos fármacos , Processamento de Proteína Pós-Traducional , Tripsina/metabolismoRESUMO
Ovarian sizes (length and width) were measured in young females of Anastrepha fraterculus (Wiedemann) (Diptera, Tephritidae) subjected or not to the inhibitor α -difluormethylornithine (α -DFMO). The most effective concentration of α -DMFO used was 50 mM and the ovarian measurements (length and width) of the treated females were smaller than those of females not treated with α -DMFO. These data may suggest some relationship between ornithine decarboxylase (ODC) and sexual maturation in A. fraterculus.
As dimensões dos ovários (comprimento e largura) foram mensuradas em fêmeas jovens da Anastrepha fraterculus (Wiedemann) (Diptera, Tephritidae) submetidas ou não ao inibidor α -difluormetilornitina (α -DFMO). A concentração mais efetiva de α -DMFO utilizada foi 50 mM e as medidas (comprimento e largura) das fêmeas tratadas com o inibidor foram menores que as fêmeas não tratadas com inibidor α -DMFO. Estes dados podem sugerir uma relação entre ornitina descarboxilase (ODC) e maturação sexual em A. fraterculus.
Assuntos
Animais , Feminino , Eflornitina/farmacologia , Inibidores Enzimáticos/farmacologia , Ornitina Descarboxilase/antagonistas & inibidores , Ovário/efeitos dos fármacos , Tephritidae/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Tephritidae/anatomia & histologia , Tephritidae/enzimologiaRESUMO
In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.
Assuntos
Reparo do DNA/genética , Redes Reguladoras de Genes , Neoplasias/genética , Mutação Puntual , Apoptose/genética , Instabilidade Genômica , HumanosRESUMO
In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.
Assuntos
Humanos , Redes Reguladoras de Genes , Neoplasias/genética , Mutação Puntual , Reparo do DNA/genética , Apoptose/genética , Instabilidade GenômicaRESUMO
Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40%) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.
Assuntos
Transtornos de Ansiedade/etiologia , Aprendizagem da Esquiva/fisiologia , Doenças do Ceco/fisiopatologia , Transtorno Depressivo/etiologia , Obstrução Intestinal/fisiopatologia , Perfuração Intestinal/fisiopatologia , Choque Séptico/fisiopatologia , Animais , Transtornos de Ansiedade/fisiopatologia , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto , Memória de Curto Prazo/fisiologia , Ratos , Ratos Wistar , Choque Séptico/psicologia , NataçãoRESUMO
Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50 percent of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40 percent) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.
Assuntos
Animais , Masculino , Ratos , Transtornos de Ansiedade/etiologia , Aprendizagem da Esquiva/fisiologia , Doenças do Ceco/fisiopatologia , Transtorno Depressivo/etiologia , Obstrução Intestinal/fisiopatologia , Perfuração Intestinal/fisiopatologia , Choque Séptico/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Modelos Animais de Doenças , Transtorno Depressivo/fisiopatologia , Aprendizagem em Labirinto , Memória de Curto Prazo/fisiologia , Ratos Wistar , Natação , Choque Séptico/psicologiaRESUMO
Pulmonary rehabilitation (PR) improves physical capacity and health quality in patients with chronic obstructive pulmonary disease (COPD). However, the effect of exercise on oxidative stress markers in COPD patients is only partially known. This study was designed to evaluate the oxidative stress response to long-term exercise in patients with COPD enrolled in a PR program. Fifteen COPD patients (FEV1 < 60%), age between 50 and 60 years, ex-smokers, were separated in two groups: exercise-trained (n=8) and sedentary group (n=7). Exercise consisted of an 8-week conditioning program using a cycle ergometer (three times a week, 1h session). An endurance test (60% of maximal load in an incremental cycle test) was performed before and after PR. Blood samples were obtained at baseline and immediately after each endurance test. We measured the index of lipid peroxidation, thiobarbituric acid reactive species (TBARS), total radical-trapping antioxidant parameter (TRAP) and xanthine oxidase (XO) activity. TRAP was significantly different between the exercise-trained group and sedentary group of COPD patients. Baseline TBARS values were increased after the exercise training program but decreased after the endurance test. XO decrease after effort in the trained and untrained groups. The results suggest that patients with COPD are characterized by increased systemic and pulmonary oxidative stress markers both at rest as well as induced by cardiopulmonary exercise test and that PR program was associated with decreased systemic exercise-induced oxidative damage.
Assuntos
Terapia por Exercício , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/reabilitação , Testes Respiratórios , Humanos , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/metabolismo , Testes de Função RespiratóriaRESUMO
The leaf extract of Passiflora alata Dryander (P. alata) has been demonstrated to possess antioxidant activity in vitro. The aim of this study was to investigate the effects of P. alata leaf extract pretreatment on carbon tetrachloride-treated rats. Male Wistar rats were randomly allocated into four groups: group 1 (control - vehicle), group 2 and 3 (P. alata extract - 1 and 5mg/kg, respectively) and group 4 (trolox - 0.18mg/kg). Rats received daily pretreatment by oral gavage for 30 days followed by a single dose of CCl(4) (3ml/kg i.p. in vegetable oil) on the 30th day and were killed after 6h. The pretreatment with the P. alata extract provided significant protection to liver, evidenced by lower degree of necrosis, decreased lipid peroxidation (TBARS) and higher catalase and superoxide dismutase activities. Additionally, pretreated-rats with P. alata (5mg/kg) showed significantly decreased cardiac TBARS levels. Our results indicate that a low oral dose of P. alata leaf extract has both hepato and cardioprotective effects on rats treated with CCl(4).