da Silva, B D B*
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Pesticides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to public and environmental health. The aim of the present study was to investigate the genotoxic potential of a commercial formulation of the fungicide mancozeb by the micronucleus test in bone marrow and the comet assay in total blood of Wistar rats. Adult male Wistar rats were treated with a solution of mancozeb at a concentration of 40 mg/kg/day, administered intraperitoneally for 18 consecutive days, and compared to a control group. The results indicate that mancozeb induced significantly higher DNA damage as detected by the comet assay and increased the frequency of micronuclei. The results show that mancozeb is genotoxic and may adversely affect the DNA integrity of exposed organisms.
- MeSH
- dithiokarb toxicita MeSH
- erytrocyty účinky léků metabolismus MeSH
- maneb toxicita MeSH
- mikrojaderné testy MeSH
- mikrojádra chromozomálně defektní účinky léků MeSH
- počet erytrocytů MeSH
- poškození DNA * MeSH
- potkani Wistar MeSH
- zineb toxicita MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling has fundamental roles in the regulation of the stem cell niche for both embryonic and adult stem cells. In zebrafish, male germ stem cell niche is regulated by follicle-stimulating hormone (Fsh) through different members of the TGF-β superfamily. On the other hand, the specific roles of TGF-β and BMP signaling pathways are unknown in the zebrafish male germ stem cell niche. Considering this lack of information, the present study aimed to investigate the pharmacological inhibition of TGF-β (A83-01) and BMP (DMH1) signaling pathways in the presence of recombinant zebrafish Fsh using testicular explants. We also reanalyzed single cell-RNA sequencing (sc-RNA-seq) dataset from adult zebrafish testes to identify the testicular cellular sites of smad expression, and to understand the physiological significance of the changes in smad transcript levels after inhibition of TGF-β or BMP pathways. Our results showed that A83-01 potentiated the pro-stimulatory effects of Fsh on spermatogonial differentiation leading to an increase in the proportion area occupied by differentiated spermatogonia with concomitant reduction of type A undifferentiated (Aund) spermatogonia. In agreement, expression analysis showed lower mRNA levels for the pluripotency gene pou5f3, and increased expression of dazl (marker of type B spermatogonia and spermatocyte) and igf3 (pro-stimulatory growth factor) following the co-treatment with TGF-β inhibitor and Fsh. Contrariwise, the inhibition of BMP signaling nullified the pro-stimulatory effects of Fsh, resulting in a reduction of differentiated spermatogonia and increased proportion area occupied by type Aund spermatogonia. Supporting this evidence, BMP signaling inhibition increased the mRNA levels of pluripotency genes nanog and pou5f3, and decreased dazl levels when compared to control. The sc-RNA-seq data unveiled a distinctive pattern of smad expression among testicular cells, primarily observed in spermatogonia (smad 2, 3a, 3b, 8), spermatocytes (smad 2, 3a, 8), Sertoli cells (smad 1, 3a, 3b), and Leydig cells (smad 1, 2). This finding supports the notion that inhibition of TGF-β and BMP signaling pathways may predominantly impact cellular components within the spermatogonial niche, namely spermatogonia, Sertoli, and Leydig cells. In conclusion, our study demonstrated that TGF-β and BMP signaling pathways exert antagonistic roles in the zebrafish germ stem cell niche. The members of the TGF-β subfamily are mainly involved in maintaining the undifferentiated state of spermatogonia, while the BMP subfamily promotes spermatogonial differentiation. Therefore, in the complex regulation of the germ stem cell niche by Fsh, members of the BMP subfamily (pro-differentiation) should be more predominant in the niche than those belonging to the TGF-β (anti-differentiation). Overall, these findings are not only relevant for understanding the regulation of germ stem cell niche but may also be useful for expanding in vitro the number of undifferentiated spermatogonia more efficiently than using recombinant hormones or growth factors.
- MeSH
- buněčná diferenciace genetika MeSH
- dánio pruhované * genetika MeSH
- folikuly stimulující hormon farmakologie metabolismus MeSH
- messenger RNA genetika MeSH
- pyrazoly * MeSH
- spermatogeneze genetika MeSH
- spermatogonie * metabolismus MeSH
- testis metabolismus MeSH
- thiosemikarbazony * MeSH
- transformující růstový faktor beta metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
To better understand the production of enzymes of industrial interest from microorganisms with biotechnological potential using lignocellulosic biomass, we evaluated the production of endoglucanase and xylanase from Aspergillus tamarii. CAZymes domains were evaluated in the genome, and a screening of the enzymatic potential of A. tamarii in various agricultural biomasses was done. The enzymatic profile could be associated with the biomass complexity, with increased biomass recalcitrance yielding higher activity. A time-course profile defined 48 h of cultivation as the best period for cultivating A. tamarii in sugarcane bagasse reached 12.05 IU/mg for endoglucanase and 74.86 IU/mg for xylanase. Using 0.1% (w/v) tryptone as the only nitrogen source and 12 μmol/L CuSO4 addition had an overall positive effect on the enzymatic activity and protein production. A 22 factorial central composite design was used then to investigate the simultaneous influence of tryptone and CuSO4 on enzyme activity. Tryptone strongly affected enzymatic activity, decreasing endoglucanase activity but increasing xylanase activity. CuSO4 supplementation was advantageous for endoglucanases, increasing their activity, and it had a negative effect on xylanases. But overall, the experimental design increased the enzymatic activity of all biomasses used. For the clean cotton residue, the experimental design was able to reach the highest enzyme activity for endoglucanase and xylanase, with 1.195 IU/mL and 6.353 IU/mL, respectively. More experimental studies are required to investigate how the biomass induction effect impacts enzyme production.
The aim of this study was to investigate the occurrence of toxic effects in liver tissue of rats treated with α-terpinene. All treatments were intraperitoneally administered at doses of 0.5, 0.75 and 1.0 ml kg−1 during 10 days. Liver samples were collected and assessed by histopathological analysis, caspases -1, -3, -8 assay, biomarkers of hepatic damage and determination of oxidant/antioxidant status (thiobarbituric acid-reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione S-transferase (GST) and glutathione peroxidase (GPx)). Additionally, the cytotoxic and genotoxic effects were evaluated by comet assay. An increase was observed on TBARS levels and GPx activity on the hepatic tissue. Instead, CAT and SOD activities decreased in rats treated with a dose of 1.0 ml kg−1 of α-terpinene. Concomitantly, ROS levels increased and GST levels decreased in rats treated with α-terpinene at doses of 0.5, 0.75 and 1.0 ml kg−1. Also, there was an increase in frequency of damage, damage index and caspases, while cell viability decreased in rats treated with α-terpinene. Alanine aminotransferase and aspartate aminotransferase increased in rats treated with 1.0 ml kg−1 of α-terpinene. Therefore, α-terpinene induces oxidative stress, cytotoxic and genotoxic effects in liver tissue involving the caspases activation.
- MeSH
- apoptóza účinky léků MeSH
- glutathiontransferasa účinky léků MeSH
- imunoanalýza MeSH
- játra * patologie účinky léků MeSH
- kaspasy * MeSH
- kometový test MeSH
- krysa rodu rattus MeSH
- monoterpeny * aplikace a dávkování toxicita MeSH
- oxidační stres MeSH
- poškození DNA účinky léků MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku analýza MeSH
- testy genotoxicity MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Klíčová slova
- úprava krevního tlaku, randomizovaná klinická studie,
- MeSH
- ambulantní monitorování metody využití MeSH
- antihypertenziva terapeutické užití MeSH
- hypertenze prevence a kontrola terapie MeSH
- lidé MeSH
- měření krevního tlaku metody využití MeSH
- randomizované kontrolované studie jako téma MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics properties to allow them crossing the blood-brain barrier, hampering cholinesterase reactivation at the central nervous system. In this work, we designed and synthesised novel isatin derivatives, linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties, and tested their reactivation potency against paraoxon- and NEMP-inhibited acetylcholinesterase in comparison to the standard antidote pralidoxime. Our results showed that these compounds displayed comparable in vitro reactivation also pointed by the in silico studies, suggesting that they are promising compounds to tackle organophosphorus poisoning.
PURPOSE: The main aim of the study was to describe the key factors involved in the preparation process of the Brazilian bronze medal kata team for the 2019 Pan American Games, focusing on the athletes' perceptions. METHODS: Three male athletes from the Brazilian team performed a semistructured interview to identify the following topics: specific time for preparation, training organization, supplementary support, and perception and suggestion about the efficiency of the preparation process. RESULTS: Data from interviews were gathered and coded, and the major themes were summarized as follows after performing content analysis of the data: (a) technical and tactical training took the major part of the preparation; (b) the high level of the coaches helped the team to reach the technical quality of the kata; (c) better psychological support during the preparation could improve the athletes' performance during the training and competition; and (d) the lack of financial support compromised the commitment of the athletes during the training routine. CONCLUSION: We concluded, based on the athletes' perception, that the most positive factor during preparation for a major competition was the high amount of time focused on technical-tactical training. Even with limitations to performing the physical training, the athletes recognized the importance of the physical component, to increase performance. Financial and psychological support could have helped the team to reach a better result (gold medal) attenuating the training distress.
- Publikační typ
- časopisecké články MeSH
Autophagy plays an essential role in body homeostasis achievement. One of the main proteins involved in this process is the LC3I, which, after lipidation, leads to the formation of LC3II that participates in the formation and maturation of autophagosome. This descriptive study verified the responses of LC3II to LC3I proteins, as well as the time-course of this ratio in mice livers after different types of acute physical exercise protocols. Eight-week-old male C57BL/6 mice were maintained three per cage with controlled temperature (22±2 °C) on a 12:12-h light-dark normal cycle with food (Purina chow) and water ad libitum. Mice were randomly divided into four groups: control (CT, sedentary mice), resistance (RE, submitted to a single bout of resistance exercise), endurance (EE, submitted to a single bout of endurance exercise), and concurrent (CE, submitted to a single bout of endurance combined with resistance exercise). The mice livers were extracted and used for the immunoblotting technique. The hepatic LC3B II/I ratio for the RE and EE groups were not altered during the different time-points. For the CE group, there was a decrease in this ratio 12h after exercise compared to time 0 and 18h. Also, the hepatic LC3B II/I ratios were not different among the acute physical exercise protocols along the time-course. The hepatic LC3B II/I ratio was not influenced by the endurance and resistance protocols but decreased in response to the concurrent protocol at 12h after the stimulus.
- MeSH
- autofagie fyziologie MeSH
- fyzická vytrvalost MeSH
- játra metabolismus MeSH
- kondiční příprava zvířat fyziologie MeSH
- kosterní svaly metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- proteiny asociované s mikrotubuly genetika metabolismus MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Carvacrol presents action in Salmonella Typhimurium biofilms, however the antibiofilm mechanism of this compound has not been fully established yet. In the present study, the aim was to evaluate protein profile changes in S. Typhimurium biofilm treated with carvacrol. Proteomic analysis of treated versus untreated biofilm showed several changes in proteins involved with S. Typhimurium biofilm and antioxidant activity. The proteins DsbA (thiol: disulfide interchange protein DsbA), LuxS (S-ribosylhomocysteine lyase), DksA (RNA polymerase binding transcription factor DksA), and SODs (superoxide dismutases) A, B and C had their synthesis decreased after treatment with carvacrol. These proteins play a key role in S. Typhimurium biofilm formation, demonstrating the dynamic antibiofilm action of carvacrol. The differentially expressed proteins identified provide possible action targets for future studies in order to gain more insight into the mechanism of action of carvacrol on S. Typhimurium biofilm.
- Klíčová slova
- karvakrol,
- MeSH
- 2D gelová elektroforéza MeSH
- antioxidancia MeSH
- biofilmy klasifikace účinky léků MeSH
- cymeny * MeSH
- hmotnostní spektrometrie MeSH
- proteiny analýza klasifikace účinky léků MeSH
- proteomika MeSH
- Salmonella typhimurium * patogenita účinky léků MeSH
- volné radikály MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
