Mestrado em Ciências Biológicas (ICB)

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Desenvolvimento e validação de um teste molecular rápido e visual para detecção de Sporothrix spp. por Amplificação Isotérmica Mediada por Loop
(Universidade Federal de Goiás, 2024-10-08) Santos, Isabela Cristina de Oliveira dos; Silva, Lívia do Carmo; http://lattes.cnpq.br/7092484043564604; Lacerda, Elisângela de Paula Silveira; http://lattes.cnpq.br/9390789693192751; Lacerda, Elisângela de Paula Silveira; Silva, Lívia do Carmo; Anunciação, Carlos Eduardo; Ferreira Júnior, Álvaro
Embargado
Criação de modelo de neuroesfera a partir de células-tronco da polpa dentária para o estudo de Hemiplegia Alternante da Infância
(Universidade Federal de Goiás, 2024-12-05) Cunha, Júlia Cristina Lucio da; Leite, Jacqueline Alves; http://lattes.cnpq.br/0714922922038212; Leite, Jacqueline Alves; Cortes, Vanessa Faria; Carvalho, Renata Karine de
Embargado.
Extração, caracterização e modificação química da goma da anadenanthera macrocarpa
(Universidade Federal de Goiás, 2014) Leal, Maria Carolina Bezerra Di Medeiros; Fernandes, Kátia Flávia
The objective of this study was to modify gum of Anadenanthera macrocarpa exudate by acetylation treatment and to evaluate its biotechnological potential as adhesive. The acetylation process was carried out under mild conditions, using acetic acid. Acetylation process of Pegico displaces pI and increases its thermal stability. The polysaccharide modification was characterized by the appearance of a new peak around 1542 cm-1 in the FTIR analysis, and in a crystalline structure characterized by sharp diffraction peaks at 14.9°, 16.8°, 17.8° and 22.5°. The acetylation also increased the swelling power of Pegicoac and reduced its solubility. Furthermore, acetylation treatment of Pegico produced higher adhesion strength in all tests conducted, characterized by an improvement in the adhesion strength in the 180° peeling test (0.205 to 0.288 N mm-1 ), in the T-peel test (0.044 to 0.088 N mm-1 ) and in the tensile bond test (0.088 to 0.133 N mm-2 ).
Atividade antigenotóxica dos extratos de Celtis iguanaea (Jacq.) Sargent e Lafoensia pacari A. St.-Hil. em células somáticas de Drosophila melanogaster
(Universidade Federal de Goiás, 2010-05) Pereira, Karla de Castro; Costa, Elson Alves; Cunha, Kênya Silva
The possibility of natural substances, derived from medicinal plants, modulate the cellular response to the mutagenic agents activity has emerged as an important mechanism in the discovery of new effective natural treatments. The aim of this work was evaluate the possible toxic, genotoxic, and antigenotoxic effects of two Brazilian Cerrado plants, which are used in folk medicine. Celtis iguanaea Jacq. Sargent (Cannabaceae), known in the state of Goiás (Brazil) as “esporão-de-galo”, has been used to treat rheumatism, asthma, body pain, colic, poor digestion, urinary infections and kidney disfunctions. Lafoensia pacari A. St.-Hil. (Lythraceae) is known popularly as “pacari” or “mangaba-brava” and has been used in traditional medicine to treat gastric ulcers, inflammation, and scar healing. The present study used the Somatic Mutation and Recombination Test (SMART), which evaluates, simultaneously, in vivo recombinational and mutational events. Third-stage larvae derived from the standard cross were used in the extract treatments. Initially, the toxicity of different concentrations of aqueous extract of leaves of Celtis iguanaea (EaqLC) and ethanol extract of leaves of Lafoensia pacari (EELL) was evaluated. The EaqLC showed no toxicity, because there was no difference between the number of surviving flies in the extract series and control treatments. Flies treated with the EELL test concentrations showed a survival rate above 40%. For genotoxic evaluation, the larvae were treated with different concentrations of EaqLC and EELL and distilled water (negative control). Both extracts did not significantly increase the frequencies of spots with mutant hair compared to negative control, so no genotoxic activity was detected. In antigenotoxic evaluation, the larvae were co-treated with different concentrations of EaqLC and EELL associated with mitomycin C (MMC), and MMC alone (positive control). The antigenotoxic analysis of trans-heterozygous individuals treated with EaqLC + MMC and EEL+MMC showed a reduction in the frequency of mutation and/or mitotic recombination due to inactivation or blockage action of these extracts on the action of MMC. The comparison of the analysis of trans-heterozygous (MH) and TM3 heterozygous (BH) descendents allowed quantifying separately the contribution of the inhibition of mutation and recombination in the total antigenotoxicity induced by the two extracts studied. This was possible because the products of recombination in BH individuals are unviable. The results showed that the proportion of mutagenic and recombinagenic events induced by EaqLC+MMC or EELL+MMC was not significantly different from MMC treatment. In summary, the overall results indicated that the EaqLC and EELL extracts do not exhibit any toxic or genotoxic effects, but were able to block or inactivate the genotoxicity of MMC, acting as desmutagenic agents.
Estudo da atividade tipo-ansiolítica das folhas de Pimenta pseudocaryophyllus (Gomes) L.R. Landrum - Myrtaceae
(Universidade Federal de Goiás, 2012) Fajemiroye, James Oluwagbamigbe; Costa, Elson Alves
Pimenta pseudocaryophyllus, popularly known as Craveiro, is the only species in this genus native to the cerrado of Brazil. Ethnopharmacological studies revealed medicinal use of P. pseudocaryophyllus extracts in treating menstrual and digestive problems as well as emotional tension in the form of soothing tea among other therapeutic applications in Brazilian folk medicine. Its popular use is of great interest given the alarming increase in neural diseases and search for innovative herbal therapy. For the purpose of this study, the ethanolic leaf extract of Pimenta pseudocaryophyllus (EEPp) was obtained by soaking the dried leaf powder in ethanol (95%, 1:5). The fractions of hexane (FH), dichloromethane (DF), ethyl acetate (EAF) and aqueous (AF) were subsequently prepared through EEPp fractionation with solvents of different polarities. Mice weighing between 25 - 35g were treated acutely (sc / p.o / i.p) for the general test of pharmacological activity while oral administration was later explored for most of the central action screening considering lack of any sign of neurotoxicity even at the highest dose (2 g/Kg). Sleep induced by barbiturates was potentiated by the ethanolic leaf extract (1 g/Kg) through prolongation of sleeping time (duration) and reduction in time taken for the loss of righting reflex (latency). Identification of the active fraction of this extract was performed using behavioural models, such as sleep induced, open field, light / dark box test (LDB) and elevated plus maze (EPM). In this manner, only EAF (0.42 g/Kg) and HF treatments did not increase sleep duration and failed to demonstrate anxiolytic like effect. Meanwhile, treatment with DF (0.25 g/Kg) and AF (0.64 g/Kg) showed an increase in sleep duration and significant alterations of time and number of crossing at the centre of the open field. The AF demonstrated sedative effect in the LDB. Meanwhile, the DF (0.125, 0.25 or 0.5 g/Kg) showed anxiolytic like activity in both the LDB and EPM in a dose- dependent manner. These results suggested the presence of active principles of the P. pseudocaryophyllus that may be useful in developing a drug for the treatment of anxiety. It is worthy to state that no sign of neurotoxicity or motor incoordination was observed with DF treatment. In an attempt to elucidate the mechanism of action involved, pre-treatment with flumazenil (antagonist of benzodiazepine site of GABAA receptor) did not block anxiolytic-like effect of DF thereby excluding the participation of this site. However, this effect was reversed by pretreatment with NAN-190 (an antagonist of the 5-HT1A). This result suggests a possible involvement of the serotonergic system. In this case the results obtained on the neuropharmacological activity of dichloromethane fraction showed promising effect in anxiety model which require further extensive study to characterize neurobiological pathways involved for possible clinical application and better understanding of the pathophysiology of this neural disorder.
Avaliação da atividade anti-inflamatória e/ou antinociceptiva de duas espécies vegetais do cerrado: Lafoensia pacari A. St. Hil e Spiranthera odoratissima A. St. Hil.
(Universidade Federal de Goiás, 2011) Nascimento, Marcus Vinícius Mariano; Silva, Roberto do Nascimento; Costa, Elson Alves
The species of plants Lafoensia pacari A. St.-Hil and Spiranthera odoratissima A. Hil St., known as “pacarí” and “manacá”, respectively, are largely used in folk medicine in the state of Goiás, Brazil. This work shows the antinociceptive and anti-inflammatory effects of ethanolic extract of stem bark of “pacarí” (PEtExt) at doses of 100, 300 and 1000 mg/kg, p.o., in different models “in vivo” in mice, such as: acetic acid-induced abdominal writhing, croton oil–induced ear edema and formalin test. After the crude extract partitioning, only the ethyl acetate fraction at dose 640 mg/kg, p.o., (EAF) showed these activities. Ellagic acid at doses of (10, 30 and 100 mg/kg, p.o.) isolated from the stem bark of “pacarí”, is the substance responsible for the anti-inflammatory activity of PEtExt and EAF, however, the ellagic acid did not show antinociceptive effect on neurogenic pain formalin test. This antinociceptive activity does not involve the participation of opioid receptors, because it was not reversed by pretreatment with naloxone at dose 3 mg/kg, s.c., (opioid receptor antagonist). The results show that PEtExt and EAF have independent analgesic activity of anti-inflammatory effect of ellagic acid. This work also shows the anti-inflammatory of methanol/aqueous phase of the ethanol extract of the leaves of “manacá” at doses of 50, 150 and 500 mg/kg, p.o., (MAP) in different models “in vivo” in mice, such as: formalin test, carrageenan-induced paw oedema. Myeloperoxidase activity, capillary permeability, leukocyte migration and TNF-α levels were evaluated in pleural exudate. The reduction in the levels of TNF-α caused by treatment with MAP may be responsible for anti-inflammatory effect observed with the “manacá” plant in different models used.
Efeito neuroreparador do ácido decanoico em modelo animal de isquemia cerebral
(Universidade Federal de Goiás, 2024-02-23) Nunes, Antonio Ítalo dos Santos; Pinto, Mauro Cunha Xavier; http://lattes.cnpq.br/0868250984727943; Pinto, Mauro Cunha Xavier; Chiareli, Raphaela Almeida; Costa, Renata Mazaro e
Cerebral ischemia is a neurological disorder that occurs due to the abrupt interruption of blood flow in the brain and can result in cognitive and motor impairments. Decanoic acid has been proposed as a potential therapeutic agent in neurological diseases as it blocks AMPA receptors and acts on neuroinflammation. In this context, the aim of this study was to investigate the effect of decanoic acid in a model of cerebral ischemia by middle cerebral artery occlusion (MCAO) in mice. For this purpose, mice received different doses of decanoic acid (62.5, 125, 250, 500, and 1000 mg/kg) or vehicle by gavage for 7 or 14 days after the induction of ischemia. Morphological analysis of the ischemic area was performed by TTC staining. Motor asymmetry, postural tone, spatial and contextual memory deficits were also evaluated using the Cylinder, Limb Clasping, OLT, and NORT tests, respectively. Furthermore, investigations of the mechanisms involved in this neurorepair were carried out by ELISA technique for inflammatory biomarkers and Western Blot to analyze AMPA receptor pathways and autophagy. The results showed that, after 7 and 14 days of treatment, decanoic acid was able to promote neurorepair effects, evidenced by the reduction of the ischemic area and improvement in motor, cognitive, and memory impairments. In addition to revealing anti-inflammatory effects, reducing the expression of pro-inflammatory cytokines, and surprisingly, this effect seems not to be related to changes in the expression of AMPA receptors or the autophagy pathway. This study suggests that decanoic acid has therapeutic potential for ischemic injuries, promoting functional and cognitive recovery, as well as acting on reducing inflammation.
Efeito neurorreparador da sarcosina no modelo de isquemia cerebral focal
(Universidade Federal de Goiás, 2024-06-28) Silva, Eduardo Rosa da; Pinto , Mauro Cunha Xavier; http://lattes.cnpq.br/0868250984727943; Pinto, Mauro Cunha Xavier; Silva, Victor Diogenes Amaral da; Colugnati, Diego Basile
Annually, approximately 17 million individuals worldwide suffer from a Stroke (Cerebrovascular Accident), a condition that can result in permanent neurological sequelae or even death. Cerebral ischemia, the primary cause of these events, is characterized by a reduction in cerebral blood flow, which can occur in a localized or generalized manner. In this context, the present study aimed to evaluate the neuroprotective and neuroreparative effects of sarcosine by investigating its influence on neuronal regeneration in animal models subjected to middle cerebral artery occlusion (MCAO). For this purpose, the animals received intraperitoneal treatment with sarcosine at doses of 125 mg/kg, 250 mg/kg, and 500 mg/kg over a period of 28 days following the induction of the MCAO model. Motor evaluation was conducted through the Limb Clasping and Cylinder behavioral tests on days 7, 14, and 28 post-inductions. Additionally, the Object Location Task (OLT) and Novel Object Recognition Test (NORT) memory tests were conducted on the 28th day. We performed molecular analysis using the Western Blotting technique to assess the expression levels related to the glycine transporter (GlyR), glycine transporters (Glyt1 and Glyt2), NMDA receptor subunits (GluN1, GluN2A, and GluN2B), proteins associated with cell survival pathways (CaMK II, CaMK IV, CREB), proteins associated with brain-derived neurotrophic factor BDNF, and TrKb. The results demonstrated that sarcosine improves motor and cognitive deficits in animals subjected to ischemia. It is concluded that sarcosine treatment shows promising neuroprotective potential in the context of ischemic stroke induced in an animal model.
Estimulação adrenérgica causada pela administração de isoproterenol induz disfunção metabólica e remodelamento pancreático em ratos Wistar
(Universidade Federal de Goiás, 2022-08-30) Castro, Alessandra Gisele de; Gomes, Rodrigo Mello; http://lattes.cnpq.br/3121095341590269; Gomes, Rodrigo Mello; Mascioli, Cristina da Costa Krewer; Custódio, Carlos Henrique Xavier
Isoproterenol is a drug commonly used for the treatment of bradycardia, heart block, bronchospasm during anesthesia and rarely for asthma. It is a non-selective β-adrenergic agonist analogue of epinephrine, for this reason it promotes positive inotropic and chronotropic effects in cardiac tissue, being used as an experimental model for the study of cardiac alterations. It is known that the adrenergic stimulation caused by the administration of isoproterenol induces cardiac remodeling, usually through pathways mainly related to redox status and inflammatory cytokines. However, little is known about the metabolic damage of this model. Thus, this study aims to evaluate the effects of isoproterenol administration on metabolic and morphological parameters. Adult Wistar rats (50-60 days old; weighing 200- 250g) were allocated into two experimental groups: control rats (CO) that received vehicle (150 mM NaCl, 0.1ml/kg/day; i.p.), and rats that received received injections of isoproterenol (ISO; 1 mg/kg/day; i.p.) for 7 consecutive days. After the treatment period, the animals were submitted to in vivo tests and later euthanized for sample collection. The animals in the ISO group did not show a significant difference in body mass compared to the CO animals. On the other hand, ISO animals showed increased brown adipose tissue mass and brown adipose area. Furthermore, the administration of isoproterenol promoted pancreatic remodeling, with an increase in the area of pancreatic islets and interstitial fibrosis. In short, in addition to cardiac changes, the adrenergic overload induced by isoproterenol administration was also able to promote significant morphological changes in brown adipose tissue and pancreas, these changes may be linked to changes in the heart and in other systems, thus, the study Integrated physiological training is fundamental for a better understanding of the exacerbated stimulation of β-adrenergic receptors.
Avaliação da atividade genotóxica e antigenotóxica de Celtis iguanaea (Jacq.) Sargent em bactérias e camundongos
(Universidade Federal de Goiás, 2010-02-24) Borges, Flávio Fernandes Veloso; Lee, Chen Chen; http://lattes.cnpq.br/4621907105842007
Celtis iguanaea (Jacq.) Sargent is a member of the Cannabaceae family and popularly known as esporão de galo. Ethnobotanical surveys of cerrado native plants show that the tea leaves of C. iguanaea is used in traditional medicine for body aches, asthma, cramps, poor digestion, urinary infections, kidney disfunctions, as a stimulant or as a diuretic.The purpose of the present work was to evaluate the possible cytotoxic, genotoxic and antigenotoxic effects of the leaves aqueous extract of C. iguanaea by the prophage λ induction test (SOS Inductest) and the micronucleous test in mice bone marrow. The SOS Inductest was performed according to Moreau (1976), using lysogenic WP2s(λ) and indicator RJF013 strains derived from Escherichia coli. WP2s(λ) cultures were treated with different doses of the extract (0.5, 1, 2.5, and 5 mg) (evaluation of genotoxicity) or co-treated with a single dose of MMC (0,5 mg) and different doses of extract (assessment of antigenotoxicity). Then, the treated culture was added to the indicator strain (RJF013) and both were poured on plates in LB(1/2) medium. For the evaluation of cytotoxicity, cultures of WP2s(λ) treated with different doses of extract were diluted in M9 buffer and plated on LB. The micronucleus test was carried out according to Schmid (1975). To assess the genotoxic activity, animals were treated with Celtis iguanaea extract (100, 300 and 500 mg/kg concentrations). To evaluate the antigenotoxic activity, the same doses of extract were treated simultaneously with 4mg/Kg of MMC. The frequencies of micronucleated polychromatic erythrocytes (MNPCE) were evaluated at 24h and 48h exposure period except the negative control (24h). The cytotoxicity was assessed by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). In both tests the obtained results demonstrated anticytotoxic activity and absence of genotoxicity and cytotoxicity of the Celtis iguanaea leaves extract. The extract also showed partial antigenotoxic activity in bacteria and antigenotoxic activity in mice.
Planejamento e síntese de novos candidatos a protótipos de fármacos anti-crises epiléticas
(Universidade Federal de Goiás, 2023-03-06) Rocha, André Luis Batista da; Arruda, Evilanna Lima; http://lattes.cnpq.br/5628078681357268; Menegatti, Ricardo; https://orcid.org/0000-0001-5044-9234; Rocha, André Luis Batista da; Menegatti, Ricardo; Colugnati, Diego Basile; Martins, Táric Ramon Marques
Epilepsy is a disease that affects about 50 million people worldwide and the worldwide prevalence is estimated at 1% of the population, and of this global rate, about 30% of patients are refractory to pharmacological treatment. In Brazil, 150 thousand new cases are registered per year. Therefore, this study aims at planning and developing new candidates for prototype anti-epileptic seizure drugs that are safer, more effective and that present fewer adverse reactions, or that can be used as a pharmacological tool. In this situation, the work describes the synthesis of compounds analogous to stiripentol. Ring bioisosterism and hybridization strategies were employed in the planning. To obtain the compounds, a synthetic route with four steps was chosen. The intermediate compound was obtained through the aldol condensation method and the final compound was obtained by the Luche reduction method, which obtained an overall yield in the range of 21% to 23%. The synthesized compounds, with the exception of compound LQFM 311, were within the parameters established by Lipinski and Verber. The compounds obtained in the synthesis were purified by recrystallization method employing solvent mixture and the purification of compound LQFM 311 was performed by column adsorption chromatography. All synthesized compounds were characterized by hydrogen nuclear magnetic resonance (¹H NMR) and ¹³C nuclear magnetic resonance (HSQC and HMBC). This demonstrates that the chosen synthetic route was adequate, allowing the development of new drug prototypes.
Efeitos da restrição alimentar severa e moderada durante a lactação sobre parâmetros metabólicos e morfológicos maternais e parâmetros cardiovasculares na prole na idade adulta
(Universidade Federal de Goiás, 2022-07-26) Cavalcante, Keilah Valéria Naves; Gomes, Rodrigo Mello; http://lattes.cnpq.br/3121095341590269; Pedrino, Gustavo Rodrigues; http://lattes.cnpq.br/1155446449250341; Pedrino, Gustavo Rodrigues; Costa, Renata Mazaro; Ferreira, Patricia Maria
Diseases developed in adulthood may be associated with conditions to which the individual was exposed in the early stages of life. It has long been postulated that changes in fetal development can trigger different effects on the newborn's quality of life. However, the great responsiveness to environmental/nutritional stimuli in postnatal phases such as lactation and puberty has been reported in the literature as an important factor in long-term phenotypic adaptation. Lactation is an important period of development, mainly due to leptin arises where the neuroendocrine circuitry is consolidated, so breast milk is the main source of nutrients for puppies in this growth phase. The objective of this study was to evaluate the effects caused on mothers due to food intervention, and the effects on cardiovascular parameters in the offspring, of both sexes, of mothers submitted to malnutrition during lactation. Pregnant Wistar rats were allocated to one of three experimental groups: Control (CO) to which a standard diet was offered ad libitum; Moderate Food Restriction (MFR, Moderate Food Restriction) for which a diet restricted to 50% of the daily consumption of the CO mothers was offered; and Severe Food Restriction (SFR) for which a low-protein diet (4.5 g protein / 100 g ration) was offered ad libitum. To maintain equity between litters, after calving all litters were adjusted to 9 pups (balancing the numbers of males and females). Feeding interventions were performed from the 1st to the 14th day of lactation, and from the 14th to the 21st day of lactation all dams received a standard diet ad libitum. The offspring of all groups were fed a standard rodent diet ad libitum throughout the experimental period. All animals were offered filtered water ad libitum. During the food intervention, the body mass and food intake of the mothers were monitored, and after weaning, samples were collected for serum biochemical measurements (Total Proteins, Albumin, Total Cholesterol, Triglycerides, HDL, TGO, Alkaline Phosphatase and Glucose) and breast milk. (Total proteins and Triglycerides), and histological analyzes (diameter of cardiomyocytes and thickness of the aorta). The offspring were followed up until 120 days of age, when the echocardiogram, invasive blood pressure recording, baroreflex test and vascular reactivity were performed. morphometric evaluation and sample collection. The protocols were approved by the UFG ethics committee (case number 023/2015). MFR mothers had reduced caloric and macronutrient intake due to the 50% food restriction protocol and had reduced ovarian adipose tissue weight. The SFR mothers showed a reduction in food intake, and consequently, there was a reduction in caloric and macronutrient intake, and a decrease in heart mass and an increase in brown adipose tissue. Males in the MFR group showed cardiovascular changes, such as increased blood pressure (BP), impaired baroreceptor sensitivity, cardiac remodeling, and changes in vascular reactivity. In contrast, males in the SFR group did not show changes in BP and cardiac tissue, however there was a loss in the sensitivity of the baroreceptors. Females from both food restriction groups did not show any cardiovascular changes, which indicates a cardioprotective effect when compared to their opposite sex pairs, possibly this cardioprotection is conferred by estrogen. Based on the results found, we conclude that moderate food restriction during lactation promotes functional and morphological cardiovascular changes in males in adulthood.
Diversidade, relações filogenéticas e perfil de expressão gênica de transportadores MFS em Trichoderma spp
(Universidade Federal de Goiás, 2021-04-21) Barbosa Filho, Jomal Rodrigues; Georg, Raphaela de Castro; http://lattes.cnpq.br/3971276154067590; Georg, Raphaela de Castro; Coelho, Alexandre Siqueira Guedes; Steindorff, Andrei Stecca
The Trichoderma genus comprises filamentous fungi with mycoparasitism ability and high tolerance to abiotic stresses, such as the presence of metals. In both conditions, cellular transporters are vital to nutrients absorption and metallic ion extrusion. Among those, the Major Facilitator Superfamily (MFS) correspond to the largest superfamily of secondary transporters found in every organism, however a deep understanding of those is needed in Trichoderma spp. The present work aimed to identify the MFS transporters from 32 species of this genus, as well as to study their phylogenetic relationship and gene expression profiles. Global MFS identification were performed in silico using the Trichoderma spp. reference proteomes available on the Mycocosm database from Joint Genome Institute (JGI), by searching for annotated aminoacid sequences using the BlastP tool. The sequences were categorized in their respective families, according to reference sequences from the Transporter Classification Database (TCDB), and maximum likelihood phylogenetic trees were estimated for each of the families, using the IQTREE software. Lastly, MFS genes expression profiles were investigated during mycoparasitism and presence of metals, using RNA-Seq public data. 8,467 putative MFS were identified in Trichoderma spp., with a mean of 264 ± 51 sequences, and this number was higher than those found in other organisms. Mycoparasitic species presented a higher number of MFS. 55.5% of the sequences showed 12 transmembrane helices and 85.5% showed molecular weights between 50 and 70 kDa, with a mean of 58 kDa. In total, 24 MFS families were identified in the analyzed species, and the families regarding to nutrition, maintenance of homeostasis and cell defense showed a higher number of members. We did not observed enrichment of families in any species analyzed. In the phylogenetic inference the sequences grouped according to their functions and not to their lineage, moreover, SHS and GPH families showed subdivisions. In T. harzianum, besides a higher number of differently expressed genes during mycoparasitism, a higher number of upregulated genes was also observed in this condition compared to those in the presence of metals. In the presence of cadmium, we observed a higher downregulation of MFS genes than in the presence of aluminum. We also observed that ACS and DHA2 families were mostly differentially expressed during mycoparasitism 24 h, whilst FHS and PHS were mostly differentially expressed during the presence of aluminum 1.5 and 3.0 mg/mL, and MCT during the presence of cadmium 2.0 mg/mL. This work shed light on the description of MFS transporters and their functions during some of the biotic and abiotic stresses faced by Trichoderma spp. in the course of its development on environment.
Efeito neuroprotetor da inibição do transportador de glicina do tipo 1 em modelos animais de dano estriatal
(Universidade Federal de Goiás, 2022-12-16) Ribeiro, Raul Izidoro Ribeiro; Pinto, Mauro Cunha Xavier; http://lattes.cnpq.br/0868250984727943; Pinto, Mauro Cunha Xavier; Giacomelli, Ágatha Oliveira; Vieira, Luciene Bruno
The striatum is a region of the brain associated with motor control, with changes in its function associated with neurodegenerative diseases such as Parkinson's and Huntington's. Although several factors are related to the neurodegeneration process in these diseases, the phenomenon of excitotoxicity and excessive stimulation of NMDA receptors (NMDAR) is a common point between them. An approach to prevent excitotoxicity is associated with the blockade of GlyT-1, which promotes the increase of glycine in the synaptic cleft, promoting a profound neuromodulation process. Based on this evidence, the objective of this work was to evaluate the effect of pretreatment with a type 1 glycine transporter inhibitor (NFPS) in animal models of Parkinson's disease (PD) and Huntington's disease (HD). Open field tests, cylinder test, rotarod and apomorphine-induced rotation tests were used to monitor motor changes in the experimental models. Western Blotting technique was performed to evaluate protein expression upon treatment with NFPS. The results suggest a neuroprotective effect, by preventing a reduction in movement, reducing striatal damage, and increasing the expression of proteins related to cell survival. Taken together, our data suggest that GlyT-1 inhibition has neuroprotective potential for striatal lesions associated with HD and PD.
Efeito transgeracional da obesidade materna por superalimentação precoce sobre os parâmetros biométricos da prole na vida adulta
(Universidade Federal de Goiás, 2022-08-29) Ferreira, Lucas Araújo; Gomes, Rodrigo Mello; http://lattes.cnpq.br/3121095341590269; Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Costa, Renata Mazaro e
Among the most prevalent non-communicable diseases today, obesity stands out at increasing levels each year. More recent data from the World Health Organization (WHO) indicate that about 650 million adults are obese, that is, many of these individuals are of reproductive age. Based on this information, the present study aims to evaluate the effects of obesity induced by the maternal postnatal overfeeding model on metabolic parameters in the offspring of Wistar rats in adulthood. For this, non-obese Wistar rats with 70 days of age were placed to cross with non-obese rats, constituting the F0 generation. Three days after conception of the first generation (F1), litter reduction was carried out in the proportion of 3 female animals per litter constituted by the reduced litter group (Small Litter, SL) and 9 female animals per litter for the control groups (Normal Litter, NL). At 70 days of age, F1 rats were crossed with non-obese rats and after conception of the second generation (F2), litters were standardized to 6 pups per mother (3 male pups and 3 female pups). After weaning, the F2 generation was separated into the following experimental groups: male and female offspring from NL mothers: M-NLO and F-NLO; and pups from SL mothers: M-SLO and F-SLO. The pups were followed up to 120 days of age, when euthanasia and sample collection were performed. Both M-SLO and F-SLO offspring had higher food intake and body mass gain throughout the experimental period, presented obese phenotype, increased pancreas mass and pancreatic islet area. However, biochemical analyzes revealed that only the M-SLO offspring had an increase in plasma concentrations of glucose and triglycerides. Molecular analyzes also showed that only the M-SLO offspring had a reduction in the expression of PI3K and p-AKT/AKT ratio in the hypothalamus. Taken together, our data evidence that postnatal maternal overfeeding induces an obese phenotype in both male and female offspring during adulthood, as well as pancreatic islet remodeling. However, only in male offspring dysregulation of biochemical parameters and of the insulin pathway in the hypothalamus was observed, evidencing a sex-specific mechanism.
Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
(Universidade Federal de Goiás, 2022-11-04) Marques, Bruno Lemes; Pinto, Mauro Cunha Xavier; http://lattes.cnpq.br/0868250984727943; Pinto, Mauro Cunha Xavier; Vitorino, Fernanda Giachini; Castro, Célio José de
Stroke is characterized by a disruption in the cerebral blood supply, leading to oxygen and glucose deprivation to the tissue. Cerebral ischemia involves enhanced glutamate release, abnormal NMDAR activation, and excitotoxicity. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission through NMDA receptors, suggesting an alternative stroke therapeutic strategy. This work investigated the neuroprotective and neurorestorative potential of GlyT1 inhibition in a mouse model of focal ischemia. Swiss mice subjected to permanent middle cerebral artery occlusion (MCAO) were randomized to receive three different doses of Sarcosine (125, 250, and 500 mg/kg) or vehicle before or after ischemia. Pretreatment with 250 and 500 mg/kg of Sarcosine led to neuroprotection against stroke, as demonstrated by reduction of infarct area and neurological deficits. Moreover, GluN2A/CaMKIV/CREB and BDNF/TrKB/Akt/mTOR pathways were enhanced by sarcosine. The sarcosine neuroprotection is also related to GluN2B subunit downregulation and a decrease in CaMKIIα phosphorylation. Additionally, we observed that post-stroke treatment with higher doses of Sarcosine improves the neurorepair process, which is evidenced by the marked reduction of the infarct area and motor deficits. Therefore, sarcosine pretreatment induced neuroprotection through the BDNF/TRKB and CaMKIV/CREB pathways, both processes trigged by NMDAR activity.
Estudo morfofisiológico dos efeitos do flavonoide crisina sobre o desenvolvimento pré-puberal da próstata de gerbilos (meriones unguiculatus)
(Universidade Federal de Goiás, 2017-07-24) Ribeiro, Naiara Cristina de Souza; Perez, Ana Paula da Silva; http://lattes.cnpq.br/4180462189994601; Santos, Fernanda Cristina Alcantara dos; http://lattes.cnpq.br/3025583084190459; Santos, Fernanda Cristina Alcantara dos; Georg, Raphaela de Castro; Oliveira, Sérgio Marcelino de
The prostate is a gland of the male reproductive system accessory, but not exclusively of males, and can be found in females of various mammals. Changes in hormone metabolism mediated by exogenous substances can interfere with the activity of this gland. An example is chrysin (5,7-dihydroflavone), a natural compound found in plants. This substance modulates the action of sex hormones, interfering with the synthesis and metabolism of steroid hormones. The objective of this study was to evaluate the effects of exposure to chrysin on the prepubertal development of the prostate of gerbils of both sexes. Thirty males and 30 females of adult gerbils were used. Each of these females was maintained with a male of the same age for mating to occur. After the cubs were born, three experimental groups were formed: 1) Control (dilution vehicle); 2) chrysin (25 mg/kg/day); 3) Positive Control (1 mg/kg/week testosterone cypionate). Males and females of all groups were treated from the 15th to the 42nd postnatal life and euthanized on the 43rd day (onset of puberty) and 90 days (onset adult). The organs were submitted to morphological, stereological and Immunohistochemical analysis. The results showed that pre-pubertal exposure to chrysin did not alter the structural parameters of the prostate of pubertal gerbils, thus increasing the frequency of androgenic (AR) and alpha estrogen (ERα) receptors. Testosterone promoted an increase in the volume and secretory activity of the alveoli at this stage of development. In male and female adult animals, chrysin promoted an increase of secretory epithelium presenting highly developed prostate glands, with a high rate of cell proliferation and high secretory activity. In addition, it maintained a significant increase in the rate of cell proliferation and the frequency of AR, and ERα-positive cells. The results allowed to conclude that the pre-pubertal exposure to chrysin caused permanent changes in development, which only became noticeable in adult life. Studies indicate that pre-pubertal exposure to flavonoid chrysin causes hormonal disorders that are capable of permanently altering prostate homeostasis. Since the high consumption of these flavonoids during the developmental stages one must be more careful since chrysin permanently changes the mofophisiology of hormone-dependent organs.
Efeito antipsicótico de novos inibidores do transportador de prolina (SLC6A7)
(Universidade Federal de Goiás, 2020-05-29) Carvalho, Gustavo Almeida de; Pinto, Mauro Cunha Xavier; http://lattes.cnpq.br/0868250984727943; Pinto, Mauro Cunha Xavier; Menegatti, Ricardo; Leite, Jacqueline Alves
Schizophrenia is a serious psychiatric disorder that expresses a complex set of positive, negative and/or cognitive symptoms. Some hypotheses attempt to explain the cause of schizophrenia, one of which is the glutamatergic hypothesis based on pharmacological evidence and pathophysiological studies that point to a hypofunction of NMDA receptor signaling in the brain. Proline transporters (SLC6A7) are predominantly expressed in the central nervous system (CNS) and are associated with glutamatergic neurotransmission, however, their role in regulating neural function and pharmacological potential is little known. The objective of this work was to pharmacologically characterize new prototypes of proline transporter inhibitors (SLC6A7) and to test the effect of one of these in a ketamine-induced psychosis model. The results presented here demonstrate that the compounds LQFM 215, LQFM 216 and LQFM 217 have a low impact on the viability of LUHMES cells and in culture of peripheral neurons and are capable of reducing the uptake of intracellular proline in synaptosomes. The compound LQFM 215 had a greater impact on the viability of LUHMES cells as well as on peripheral neurons and a greater inhibitory effect on the uptake of proline. In the behavior of mice, the compound LQFM 215 reduced the mobility of the animals, without prejudice to the working memory in the highest tested dose of 10 mg/kg and was not able to induce anxious or depressive behaviors. In the marble burying test the compound LQFM 215 in all the tested doses of 2.5, 5 and 10 mg/kg was able to stimulate this behavior. By testing the compound LQFM 215 in the ketamine-induced psychosis model, he was able to reduce the animals' induced hyperlocomotion at the tested doses of 20 and 30 mg/kg. The set of these results indicates that the compound LQFM 215 is a neuroactive compound with an effect on the mobility of animals and with antipsychotic potential. This work demonstrates that PROT inhibitors can be targets for the development of new antipsychotics.
Avaliação da atividade genotóxica, citotóxica e histopatológica de imunossupressores em diversos níveis celulares e organismos
(Universidade Federal de Goiás, 2019-08-29) Oliveira, Laís Camargo de; Carneiro, Cristiene Costa; http://lattes.cnpq.br/9930282180386562; Lee, Chen Chen; http://lattes.cnpq.br/4621907105842007; Lee, Chen Chen; Silva, Carolina Ribeiro e; Reis, Paulo Roberto de Melo
Prednisone (PD) and azathioprine (AZA) are widely used in the immunossupressive therapy of transplanted and autoimmune disease patients. The chronic use of immunossupressants has been correlated with the occurrence of several side effects and also with the increase of neoplasia in those patients. Considering that genotoxic activity is associated to the increase of risk of cancer development, this study evaluated mutagenic, genotoxic and cytotoxic activities PD and AZA using in vitro and in vivo assays. The mutagenic activity was evaluated using mutagenicity Ames test in Salmonella typhimurium TA100 strain. The evaluation of genotoxicity and cytotoxicity was performed using micronucleus and comet assays in mouse bone marrow cells. Moreover, it was evaluated the toxic effects of PD and AZA in organs (liver and kidneys) of mice. In the mutagenic Ames test PD didn’t showed significant difference compared to the negative control in all tested doses (p > 0,05). In contrast, AZA exhibited significant increase compared to negative control in the two higher doses (20 and 40 μg/plate) (p < 0,05). In the micronucleus test, PD showed genotoxic activity in all tested doses and times and was cytotoxic in two of the tested doses (1,0 mg/kg in 48 hours and 0,5 mg/kg in 120 hours). In the comet assay, PD showed high porcentage of DNA damage in all tested doses and times. Furthermore, the 120 hours treatment presented the highest genotoxic activity when compared to the other PD tested groups (p < 0,05). In the same assay, AZA showed significant increase in all doses and times of treatment when compared with negative control (p < 0,05). In the histopathological analyzes, it was observed a moderate to accentuated congestion in mice liver treated with PD and a discrete hyperemia in mice liver when treated with AZA. Therefore, PD did not showed mutagenic activity in Ames test, however it was genotoxic and cytotoxic in the in vivo assays, and presented moderated toxic effect in the histopatological analyses. AZA exhibited mutagenic and genotoxic activity in several genotoxicological assays performed, however it did not cause relevant toxicity in mice tissues.
Crisina previne a neurotoxicidade induzida por cloreto de alumínio em camundongos swiss machos
(Universidade Federal de Goiás, 2022-01-28) Campos, Hericles Mesquita; Ghedini, Paulo César; http://lattes.cnpq.br/5789550234984454; Ghedini, Paulo César; Duarte, Djane Braz; Munhoz, Carolina Demarchi
Chronic aluminium (Al) metal accumulation contributes to the progression of several neurological and neurodegenerative diseases. In particular, Al promotes oxidative damage, neuronal death, and functional decline resulting in deficits in cognition, memory and behavior. In this regard, the use of natural antioxidants can be a strategy to prevent the neurotoxicity of Al. Chrysin is a natural phenolic compound found in foods such as honey, passion fruit, and propolis and with antioxidant and anti-inflammatory properties. Here, we evaluated the chrysin neuroprotective effects against the neurotoxicity induced by chronic exposure to aluminium chloride (AlCl3), in mice (100 mg/kg, p.o.). The experimental protocol consisted of the treatment of mice with AlCl3 for ninety consecutive days, being the chrysin administration (10, 30. 100 mg/kg, p.o.) started on the forty-sixth day of the Al intake. Chrysin reduced the cognitive impairment induced by AlCl3 in the step-down passive avoidance task, normalizing the hippocampus acetylcholinesterase and butyrylcholinesterase activities. Along with this, chrysin decreased oxidative damage observed in the parameters of the lipid peroxidation, protein carbonylation, catalase and superoxide dismutase activities in the brain cortex and hippocampus. Furthermore, necrotic cells frequency was also decreased by chrysin in the same brain regions. These results highlighted that chrysin is able to reduce the neurotoxic effects associated with Al chronic exposure, being a potential compound present in foods that can be used for the benefit of mental health.

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