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Introduction: Soybean (Glycine max) is among the most important crops in the world, and its production can be threatened by biotic diseases, such as anthracnose. Soybean anthracnose is a seed-borne disease mainly caused by the hemibiotrophic fungus Colletotrichum truncatum. Typical symptoms are pre- and post-emergence damping off and necrotic lesions on cotyledons, petioles, leaves, and pods. Anthracnose symptoms can appear early in the field, causing major losses to soybean production. Material and Methods: In preliminary experiments, we observed that the same soybean cultivar can have a range of susceptibility towards different strains of C. truncatum, while the same C. truncatum strain can cause varying levels of disease severity in different soybean cultivars. To gain a better understanding of the molecular mechanisms regulating the early response of different soybean cultivars to different C. truncatum strains, we performed pathogenicity assays to select two soybean cultivars with significantly different susceptibility to two different C. truncatum strains and analyzed their transcriptome profiles at different time points of interaction (0, 12, 48, and 120 h post-inoculation, hpi). Results and Discussion: The pathogenicity assays showed that the soybean cultivar Gm1 is more resistant to C. truncatum strain 1080, and it is highly susceptible to strain 1059, while cultivar Gm2 shows the opposite behavior. However, if only trivial anthracnose symptoms appeared in the more resistant phenotype (MRP; Gm1-1080; Gm2-1059) upon 120 hpi, in the more susceptible phenotype (MSP; Gm-1059; Gm2- 1080) plants show mild symptoms already at 72 hpi, after which the disease evolved rapidly to severe necrosis and plant death. Interestingly, several genes related to different cellular responses of the plant immune system (pathogen recognition, signaling events, transcriptional reprogramming, and defense-related genes) were commonly modulated at the same time points only in both MRP. The list of differentially expressed genes (DEGs) specific to the more resistant combinations and related to different cellular responses of the plant immune system may shed light on the important host defense pathways against soybean anthracnose.
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In addition to being an antioxidant, thioredoxin (Trx) is known to stimulate signaling pathways involved in cell proliferation and to inhibit apoptosis. The aim of this study was to explore the role of Trx in some of these pathways along the progression of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male rats were first divided into two groups: monocrotaline (MCT - 60 mg/kg i.p.) and control (received saline), that were further divided into three groups: 1, 2, and 3 weeks. Animals were submitted to echocardiographic analysis. Right and left ventricles were used for the measurement of hypertrophy, through morphometric and histological analysis. The lung was prepared for biochemical and molecular analysis. One week after MCT injection, there was an increase in thioredoxin reductase (TrxR) activity, a reduction in glutathione reductase (GR) activity, and an increase in Trx-1 and vitamin D3 up-regulated protein-1 (VDUP-1) expression. Two weeks after MCT injection, there was an increase in VDUP-1, Akt and cleaved caspase-3 activation, and a decrease in Trx-1 and Nrf2 expression. PAH-induced by MCT promoted a reduction in Nrf2 and Trx-1 expression as well as an increase in Akt and VDUP-1 expression after three weeks. The increase in pulmonary vascular resistance was accompanied by increased TrxR activity, suggesting an association between the Trx system and functional changes in the progression of PAH. It seems that Trx-1 activation was an adaptive response to MCT administration to cope with pulmonary remodeling and disease progression, suggesting a potential new target for PAH therapeutics.
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Progressão da Doença , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Tiorredoxinas/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose , Sobrevivência Celular , Colágeno/metabolismo , Eletrocardiografia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertrofia Ventricular Direita/complicações , Hipertrofia Ventricular Direita/patologia , Masculino , Monocrotalina , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hipertensão Arterial Pulmonar/complicações , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Ratos WistarRESUMO
Cancer cachexia is a severe wasting condition that needs further study to find ways to minimise the effects of damage and poor prognosis. Skeletal muscle is the most impacted tissue in cancer cachexia; thus, elucidation of its metabolic alterations could provide a direct clue for biomarker research and be applied to detect this syndrome earlier. In addition, concerning the significant changes in the host metabolism across life, this study aimed to compare the metabolic muscle changes in cachectic tumour-bearing hosts at different ages. We performed 1H-NMR metabolomics in the gastrocnemius muscle in weanling and young adult Walker-256 tumour-bearing rats at different stages of tumour evolution (initial, intermediate, and advanced). Among the 49 metabolites identified, 24 were significantly affected throughout tumour evolution and 21 were significantly affected regarding animal age. The altered metabolites were mainly related to increased amino acid levels and changed energetic metabolism in the skeletal muscle, suggesting an expressive catabolic process and diverted energy production, especially in advanced tumour stages in both groups. Moreover, these changes were more severe in weanling hosts throughout tumour evolution, suggesting the distinct impact of cancer cachexia regarding the host's age, highlighting the need to adopting the right animal age when studying cancer cachexia.
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Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.
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Autofagia , Regulação da Expressão Gênica , Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Animais , Biomarcadores/metabolismo , Masculino , CamundongosRESUMO
PURPOSE: The main goal of this study was to determine the relationship of cleaved-caspase-3 (C3)-related apoptosis and hepatic proliferation, during the liver repopulation in a living liver donor rat model. MATERIAL/METHODS: Thirty-three animals were randomized into eleven groups and evaluated on postoperative from 3 âh until 384 âh after 30%-partial hepatectomy (30%-PHx). Liver sections (5 âµm) were processed by hematoxylin-eosin, and immunostaining for C3, accompanied by hepatic function test. C3 content and the hepatic lobule enlargement were analyzed by optical density, followed by cell counting. RESULTS: Transient variations of alanine transferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were found. Significant increase in the C3 levels, and cell nuclei number, were detected at 12 âh and 48 âh after 30%-PHx, evidencing a correlation of p â= â-0.3679. CONCLUSION: In the 30%-PHx rat model, C3-related apoptosis prevents proliferative pathological conditions during the hepatic lobule re-modeling.
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Apoptose , Caspase 3/metabolismo , Proliferação de Células , Hepatectomia/métodos , Regeneração Hepática , Fígado/patologia , Animais , Caspase 3/genética , Doadores Vivos/estatística & dados numéricos , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: We sought to determine the time course of changes in neuromuscular performance and muscle damage following a single rugby union match. METHODS: Fourteen male amateur rugby players (28.9 ± 3.5 yrs; 1.7 ± 5.1 m; 86.1 ± 11.1 kg) participated. Plasma activity of creatine kinase ([CK]) and lactate dehydrogenase (LDH), L-run test (change of direction) and 30-m sprint (T30; speed) with 10-m lap time (T10; acceleration) were assessed on six occasions: one week before the match (PRE) and immediately, 24, 48, 72, and 96 h post-match. RESULTS: Relative to PRE, LDH was elevated immediately post-match (+33.6% ± 13.6%; p < 0.001) and [CK] was elevated immediately (+64.1% ± 38.8%, p = 0.001) and 24 h post-match (+352% ± 317%; p = 0.024). L-run test time increased 16.0 ± 8.7% relative to PRE at 24 h post (p < 0.001) and remained elevated through 96 h post-match (p < 0.05). T10 and T30 times increased relative to PRE immediately post-match (+12.0% ± 10.4%, p = 0.008; and +6.1% ± 4.9%; p = 0.006, respectively), though T30 times were similar to baseline by 48 h post-match whereas T10 times remained elevated through 72 h post-match. CONCLUSIONS: A single, competitive rugby union match induces significant muscle damage and performance decrements with distinct time courses of recovery in amateur athletes. Notably, change of direction attributes (i.e., L-run) appear to have the longest time course to full recovery.
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Eucalyptus rust is caused by the biotrophic fungus, Austropuccinia psidii, which affects commercial plantations of Eucalyptus, a major raw material for the pulp and paper industry in Brazil. In this manuscript we aimed to uncover the molecular mechanisms involved in rust resistance and susceptibility in Eucalyptus grandis. Epifluorescence microscopy was used to follow the fungus development inside the leaves of two contrasting half-sibling genotypes (rust-resistance and rust-susceptible), and also determine the comparative time-course of changes in metabolites and proteins in plants inoculated with rust. Within 24 h of complete fungal invasion, the analysis of 709 metabolomic features showed the suppression of many metabolites 6 h after inoculation (hai) in the rust-resistant genotype, with responses being induced after 12 hai. In contrast, the rust-susceptible genotype displayed more induced metabolites from 0 to 18 hai time-points, but a strong suppression occurred at 24 hai. Multivariate analyses of genotypes and time points were used to select 16 differential metabolites mostly classified as phenylpropanoid-related compounds. Applying the Weighted Gene Co-Expression Network Analysis (WGCNA), rust-resistant and rust-susceptible genotypes had, respectively, 871 and 852 proteins grouped into 5 and 6 modules, of which 5 and 4 of them were significantly correlated to the selected metabolites. Functional analyses revealed roles for photosynthesis and oxidative-dependent responses leading to temporal activity of metabolites and related enzymes after 12 hai in rust-resistance; while the initial over-accumulation of those molecules and suppression of supporting mechanisms at 12 hai caused a lack of progressive metabolite-enzyme responses after 12 hai in rust-susceptible genotype. This study provides some insights on how E. grandis plants are functionally modulated to integrate secondary metabolites and related enzymes from phenylpropanoid pathway and lead to temporal divergences of resistance and susceptibility responses to rust.
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Fish oil, a rich source of n-3 fatty acids, has been studied for its beneficial effects in many diseases. Recent studies have shown the robust anti-inflammatory activity of fish oil (FO), when administered orally to rats, in models of acute inflammation. Herein, we investigated if treatment with fish oil preparation (FOP) could interfere with the recruitment of leukocytes into the joint cavity of arthritic rats. We also evaluated the effect of treatment on rolling behavior and leukocyte adhesion in vivo and on leukocyte chemotaxis in vitro. Treatment with FOP (75, 150, and 300 mg/kg) initiated on the day of induction of arthritis (day 0) and maintained for 21 days reduced the total number of leukocytes recruited into the joint cavity, the number of rolling and adhered leukocytes in arthritic rats, and leukocyte migration in response to stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and leukotriene B4 (LTB4). Together, our data provide evidence that FOP plays an important inhibitory role in the recruitment of leukocytes into the joint cavity of arthritic rats.
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Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Quimiotaxia de Leucócito/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Articulações/imunologia , Articulações/patologia , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucotrieno B4/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Hypocotyls/roots of four (anthracnose-resistant: ICA Quimbaya and CORPOICA 106; anthracnose-susceptible: Cargamanto Rojo and Cargamanto Mocho) common bean cultivars treated with salicylic acid (SA) as elicitor, were analyzed to determine the capacity for synthesizing defense-related isoflavonoids. Time-course and dose-response studies indicated that the maximum levels of isoflavonoids, occurred at 1.45 mM SA and between 96 and 144 h post-induction. Overall, anthracnose-resistant cultivars produced the defense-related isoflavonoids to superior amounts than the susceptible ones. Additionally, crude isoflavonoid extracts from SA-treated tissues cvs. ICA Quimbaya and Cargamanto Rojo displayed higher inhibitory effect against C. lindemuthianum than those from water-treated tissues. A comparison of the isoflavonoid-eliciting activity of a series of structurally-related compounds to SA revealed that isoflavonoid production may be differentially controlled. Acetyl-salicylic acid showed the best isoflavonoid-inducing effect. Results might be useful for crop protection programs through the selecting of common bean cultivars with better prospects of disease resistance, and the development of better isoflavonoid-eliciting agents.
Los hipocótilos/raíces de cuatro variedades de poroto (resistente a antracnosis: ICA Quimbaya y CORPOICA 106; susceptible a antracnosis: Cargamanto Rojo y Cargamanto Mocho) tratados con ácido salicílico (AS) como elicitor, se analizaron para determinar la capacidad para sintetizar isoflavonoides relacionados con la defensa. Los estudios en el curso del tiempo y dosis-respuesta indicaron que los niveles máximos de isoflavonoides, ocurrieron a una concentración de AS de 1.45 mM y entre 96 y 144 h post-inducción. En general, las variedades resistentes a la antracnosis produjeron los isoflavonoides relacionados con la defensa en cantidades superiores en comparación con las variedades susceptibles. Adicionalmente, los extractos de isoflavonoides crudos provenientes de tejidos tratados con AS var. ICA Quimbaya y Cargamanto Rojo desplegaron un efecto inhibitorio contra C. lindemuthianum mayor que aquellos resultantes de tejidos tratados con agua. Una comparación de la actividad inductora de isoflavonoides de una serie de compuestos estructuralmente relacionados con el AS reveló que la producción de isoflavonoides puede ser controlada diferencialmente. El ácido acetilsalicílico mostró el mejor efecto inductor de isoflavonoides. Los resultados pueden ser útiles para los programas de protección a cultivos a través de la selección de variedades con mejores perspectivas de resistencia a enfermedades, y el desarrollo de mejores agentes elicitores de isoflavonoides.
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Antifúngicos , Ácido Salicílico/administração & dosagem , Colletotrichum , Flavonoides , Phaseolus , Cumestrol , Relação Dose-Resposta a DrogaRESUMO
The occurrence of a weak auditory warning stimulus increases the speed of the response to a subsequent visual target stimulus that must be identified. This facilitatory effect has been attributed to the temporal expectancy automatically induced by the warning stimulus. It has not been determined whether this results from a modulation of the stimulus identification process, the response selection process or both. The present study examined these possibilities. A group of 12 young adults performed a reaction time location identification task and another group of 12 young adults performed a reaction time shape identification task. A visual target stimulus was presented 1850 to 2350 ms plus a fixed interval (50, 100, 200, 400, 800, or 1600 ms, depending on the block) after the appearance of a fixation point, on its left or right side, above or below a virtual horizontal line passing through it. In half of the trials, a weak auditory warning stimulus (S1) appeared 50, 100, 200, 400, 800, or 1600 ms (according to the block) before the target stimulus (S2). Twelve trials were run for each condition. The S1 produced a facilitatory effect for the 200, 400, 800, and 1600 ms stimulus onset asynchronies (SOA) in the case of the side stimulus-response (S-R) corresponding condition, and for the 100 and 400 ms SOA in the case of the side S-R non-corresponding condition. Since these two conditions differ mainly by their response selection requirements, it is reasonable to conclude that automatic temporal expectancy influences the response selection process.
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Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Atenção/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Estimulação Acústica/métodosRESUMO
Este trabajo revisa en qué medida el tratamiento farmacológico incide en el curso crónico de la esquizofrenia y de la depresión unipolar. Se propone contestar tres preguntas: ¿produce la curación del trastorno?; ¿incide significativamente en su evolución sintomática?; ¿limita o modifica sustancial mente la discapacidad resultante? A partir de analizar conceptualmente la bibliografía disponible, se concluye que los antipsicóticos mejoran el curso sintomático de la esquizofrenia, aunque su eficacia es limitada, y que no tienen incidencia en la discapacidad que acompaña al trastorno. Con respecto a la depresión se observa que un porcentaje importante de pacientes permanece sintomático a pesar de recibir tratamientos adecuados. No hay datos acerca de la eficacia de la farmacoterapia en la potencial discapacidad resultante de la depresión unipolar.
This work summarizes the efficacy of pharmacotherapy does it cure these diseases? Does it exert any significant effect on the symptomatic presentation of the disorders? Which is its action on the social dysfunction provoked by schizophrenia or depression?A conceptual analysis of available bibliography was performed. It could be concluded that antipsychotics improve the symptomatic course of schizophrenia, although their efficacy is limited, and that these drugs does not act on the social dysfunction provoked by the disease. With respect to depression, it could be concluded that a significant proportion of patients remain symptomatic despite receiving adequate treatments. No data about efficacy of pharmacotherapy on the dysfunction resultant from unipolar depression is available.
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Humanos , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Tempo , Esquizofrenia/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Doença Crônica , Transtornos MentaisRESUMO
Este trabajo revisa en qué medida el tratamiento farmacológico incide en el curso crónico de la esquizofrenia y de la depresión unipolar. Se propone contestar tres preguntas: ¿produce la curación del trastorno?; ¿incide significativamente en su evolución sintomática?; ¿limita o modifica sustancial mente la discapacidad resultante? A partir de analizar conceptualmente la bibliografía disponible, se concluye que los antipsicóticos mejoran el curso sintomático de la esquizofrenia, aunque su eficacia es limitada, y que no tienen incidencia en la discapacidad que acompaña al trastorno. Con respecto a la depresión se observa que un porcentaje importante de pacientes permanece sintomático a pesar de recibir tratamientos adecuados. No hay datos acerca de la eficacia de la farmacoterapia en la potencial discapacidad resultante de la depresión unipolar.(AU)
This work summarizes the efficacy of pharmacotherapy does it cure these diseases? Does it exert any significant effect on the symptomatic presentation of the disorders? Which is its action on the social dysfunction provoked by schizophrenia or depression?A conceptual analysis of available bibliography was performed. It could be concluded that antipsychotics improve the symptomatic course of schizophrenia, although their efficacy is limited, and that these drugs does not act on the social dysfunction provoked by the disease. With respect to depression, it could be concluded that a significant proportion of patients remain symptomatic despite receiving adequate treatments. No data about efficacy of pharmacotherapy on the dysfunction resultant from unipolar depression is available.(AU)
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Humanos , Esquizofrenia/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Tempo , Transtornos Mentais , Doença CrônicaRESUMO
The effect of different contextual stimuli on different ethanol-induced internal states was investigated during the time course of both the hypothermic effect of the drug and of drug tolerance. Minimitters were surgically implanted in 16 Wistar rats to assess changes in their body temperature under the effect of ethanol. Rat groups were submitted to ethanol or saline trials every other day. The animals were divided into two groups, one receiving a constant dose (CD) of ethanol injected intraperitoneally, and the other receiving increasing doses (ID) during the 10 training sessions. During the ethanol training sessions, conditioned stimuli A (tone) and B (buzzer) were presented at "state +" (35 min after drug injection) and "state -" (170 min after drug injection), respectively. Conditioned stimuli C (bip) and D (white noise) were presented at moments equivalent to stimuli A and B, respectively, but during the saline training sessions. All stimuli lasted 15 min. The CD group, but not the ID group, developed tolerance to the hypothermic effect of ethanol. Stimulus A (associated with drug "state +") induced hyperthermia with saline injection in the ID group. Stimulus B (associated with drug "state -") reduced ethanol tolerance in the CD group and modulated the hypothermic effect of the drug in the ID group. These results indicate that contextual stimuli acquire modulatory conditioned properties that are associated with the time course of both the action of the drug and the development of drug tolerance.