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1.
PLoS Pathog ; 20(7): e1012336, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39018347

RESUMO

Cullin-1-RING ubiquitin ligases (CRL1) or SCF1 (SKP1-CUL1-RBX1) E3 ubiquitin ligases are the largest and most extensively investigated class of E3 ligases in mammals that regulate fundamental processes, such as the cell cycle and proliferation. These enzymes are multiprotein complexes comprising SKP1, CUL1, RBX1, and an F-box protein that acts as a specificity factor by interacting with SKP1 through its F-box domain and recruiting substrates via other domains. E3 ligases are important players in the ubiquitination process, recognizing and transferring ubiquitin to substrates destined for degradation by proteasomes or processing by deubiquitinating enzymes. The ubiquitin-proteasome system (UPS) is the main regulator of intracellular proteolysis in eukaryotes and is required for parasites to alternate hosts in their life cycles, resulting in successful parasitism. Leishmania UPS is poorly investigated, and CRL1 in L. infantum, the causative agent of visceral leishmaniasis in Latin America, is yet to be described. Here, we show that the L. infantum genes LINF_110018100 (SKP1-like protein), LINF_240029100 (cullin-like protein-like protein), and LINF_210005300 (ring-box protein 1 -putative) form a LinfCRL1 complex structurally similar to the H. sapiens CRL1. Mass spectrometry analysis of the LinfSkp1 and LinfCul1 interactomes revealed proteins involved in several intracellular processes, including six F-box proteins known as F-box-like proteins (Flp) (data are available via ProteomeXchange with identifier PXD051961). The interaction of LinfFlp 1-6 with LinfSkp1 was confirmed, and using in vitro ubiquitination assays, we demonstrated the function of the LinfCRL1(Flp1) complex to transfer ubiquitin. We also found that LinfSKP1 and LinfRBX1 knockouts resulted in nonviable L. infantum lineages, whereas LinfCUL1 was involved in parasite growth and rosette formation. Finally, our results suggest that LinfCul1 regulates the S phase progression and possibly the transition between the late S to G2 phase in L. infantum. Thus, a new class of E3 ubiquitin ligases has been described in L. infantum with functions related to various parasitic processes that may serve as prospective targets for leishmaniasis treatment.

2.
J Med Virol ; 96(3): e29551, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506236

RESUMO

Respiratory Syncytial Virus (RSV) is an important cause of respiratory infection in humans. Severe cases are common in children ≤2 years old, immunocompromised individuals, and the elderly. In 2020, RSV infection reduced in Rio Grande do Sul (RS), southern Brazil; however, in 2021 resurgence of RSV was observed. This study analyzed epidemiological and genetic features of RSV infection cases reported in 2021 in RS. Nasopharyngeal samples collected from individuals with respiratory infection negative for SARS-CoV-2, Influenza A and B viruses were assessed for the presence of RSV by real time RT-qPCR. RSV-A and RSV-B genomic sequencing and phylogenetic reconstructions were performed for genotyping and clade characterization. Among 21,035 respiratory samples analyzed, 2,947 were positive for RSV, 947 of which were hospitalized patients. Positive cases were detected year-round, with the highest number in June-July (winter). Children <1 year comprised 56.28% (n = 533) of the hospitalized patients infected with RSV, whereas 14.46% (n = 137) were individuals >60 years. Of a total of 361 deaths, 14.68% (n = 53) were RSV positive, mostly patients >60 years old (73.58%, n = 39). Chronic kidney disease, cardiopathy, Down syndrome and neurological diseases were associated with RSV infection. RSV-A was identified in 58.5% (n = 117/200) of the patients, and RSV-B in 41.5% (n = 83/200). Of 95 RSV genomes recovered from SARI cases, 66 were RSV-A GA.2.3.5 genotype, while 29 were RSV-B GB.5.0.5a genotype. This study provides epidemiological and molecular data on RSV cases in RS during the COVID-19 pandemic and highlights that investigation of different respiratory viruses is essential for decision-making and disease prevention and control measures.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Humanos , Lactente , Idoso , Pré-Escolar , Pessoa de Meia-Idade , Vírus Sincicial Respiratório Humano/genética , Infecções por Vírus Respiratório Sincicial/epidemiologia , Filogenia , Brasil/epidemiologia , Pandemias , COVID-19/epidemiologia , SARS-CoV-2/genética , Influenza Humana/epidemiologia
3.
Microb Cell Fact ; 23(1): 51, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355518

RESUMO

BACKGROUND: In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. L-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. L-lysine α-oxidase, a flavoenzyme that degrades L-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of L-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. RESULTS: The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. CONCLUSIONS: The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.


Assuntos
Hypocreales , Leucemia , Neoplasias , Trichoderma , Humanos , Lisina , Apoptose , Leucemia/tratamento farmacológico , Necrose
4.
Environ Res ; 258: 119409, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38871272

RESUMO

Meropenem is a potent carbapenem antibiotic frequently used in medical settings. Several studies have confirmed the pervasive presence of these antibiotics in wastewater treatment plants and aquatic environments. However, the effects of these substances on non-target organisms, such as plants, have not been adequately monitored. Thus, this study aimed to assess the short-term impact of meropenem on the growth, photosynthesis, chlorophyll content, and enzyme activity of the macrophyte plant Lemna minor. The methods involved exposing the plant to meropenem under controlled conditions and assessing physiological and biochemical parameters to determine the impact on photosynthetic activity and oxidative stress. These analyses included growth rate, antioxidant enzyme activity, and photosynthetic capacity. The findings suggest that the growth rate of Lemna minor remained unaffected by meropenem at concentrations <200000 µgL-1. However, plants exposed to concentrations >20 µgL-1showed physiological alterations, such as decreased net photosynthesis rate (17%) and chlorophyll concentration (57%), compared to the control group. For acute toxicity assays, the calculated EC50 7-day and EC20 7-day were 1135 µgL-1and 33 µgL-1, respectively. In addition, in most treatments tested, meropenem caused an increase in the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity as a defense mechanism against oxidative stress. Our results suggest that meropenem affects photosynthetic processes and induces oxidative stress in the macrophyte plant Lemna minor. Further studies are needed to assess the physiological and metabolic interactions between antibiotics and primary producers at different long-term trophic levels.

5.
Glob Chang Biol ; 29(2): 391-403, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36203244

RESUMO

Approximately half of the global annual production of wastewater is released untreated into aquatic environments, which results in worldwide organic matter pollution in urban rivers, especially in highly populated developing countries. Nonetheless, information on microbial community assembly and assembly-driving processes in organic matter-polluted urban rivers remains elusive. In this study, a field study based on water and sediment samples collected from 200 organic matter-polluted urban rivers of 82 cities in China and Indonesia is combined with laboratory water-sediment column experiments. Our findings demonstrate a unique microbiome in these urban rivers. Among the community assembly-regulating factors, both organic matter and geographic conditions play major roles in determining prokaryotic and eukaryotic community assemblies, especially regarding the critical role of organic matter in regulating taxonomic composition. Using a dissimilarity-overlap approach, we found universality in the dynamics of water and sediment community assembly in organic matter-polluted urban rivers, which is distinctively different from patterns in eutrophic and oligotrophic waters. The prokaryotic and eukaryotic communities are dominated by deterministic and stochastic processes, respectively. Interestingly, water prokaryotic communities showed a three-phase cyclic succession of the community assembly process before, during, and after organic matter pollution. Our study provides the first large-scale and comprehensive insight into the prokaryotic and eukaryotic community assembly in organic matter-polluted urban rivers and supports their future sustainable management.


Assuntos
Microbiota , Rios , Cidades , Água , China
6.
Physiol Plant ; 174(1): e13595, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34766358

RESUMO

Increasing global temperatures could result in decreasing crop production by decreasing seed germination in the field due to thermodormancy acquisition. Certain metals appear to modulate seed thermodormancy, although the exact mechanisms of that effect have not yet been elucidated. We report here the effects of Zn on the thermodormancy of sorghum seeds. Seeds treated with 0 or 200 mg Zn L-1 were germinated at optimal (30°C) and supra-optimal (40°C) temperatures and their germinability and oxidative stress markers were evaluated. The integrative effects of Zn, abscisic acid (ABA), gibberellin (GA), and H2 O2 on the physiology of seed thermodormancy were examined. The supra-optimal germination temperature (40°C) induced seed thermodormancy, which was, however, alleviated by treatment with 200 mg Zn L-1 . Thermodormancy acquired at supra-optimal temperatures in sorghum seeds must reflect de novo synthesis and accumulation of ABA. Although Zn treatment did not prevent ABA accumulation, it increased the activities of mitochondrial ETC enzymes and decreased the antioxidant enzymes' activity, leading to the accumulation of H2 O2 . By increasing mitochondria activity and H2 O2 production, Zn may induce GA synthesis and alleviate thermodormancy in sorghum seeds. The pretreatment of sorghum seeds with Zn may therefore improve seed germination and assure increased crop performance under normal (30°C) or rising (up to 40°C) temperatures.


Assuntos
Giberelinas , Sorghum , Ácido Abscísico/farmacologia , Germinação , Giberelinas/farmacologia , Peróxido de Hidrogênio/farmacologia , Sementes/fisiologia , Zinco/farmacologia
7.
Int J Phytoremediation ; 24(9): 995-1003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34686072

RESUMO

Water contamination by antibiotics is an emerging global problem, with impacts on both public health and the environment. Erythromycin has been encountered in bodies of water throughout the world, which demands the development of efficient remediation technologies. We investigated the physiological responses and phytoremediation capacity of four species of aquatic macrophytes, two floating (Salvinia molesta and Lemna minor) and two submerged (Myriophyllum aquaticum and Rotala rotundifolia). The plants were exposed to relevant environmental concentrations of erythromycin (0 and 1.7 µg l-1) in artificially contaminated water for seven days. Physiological evaluations evidenced the ability of that antibiotic to promote oxidative events in those plants, such as the activation of antioxidant enzymes (ascorbate peroxidase and/or catalase). S. molesta exposed to erythromycin demonstrated accumulations of hydrogen peroxide and oxidative damage (lipid peroxidation) that was reflected in growth reductions. The erythromycin removal efficiency of floating plants varied from 9 to 12%, while submerged species varied from 31 to 44%. As such, submerged macrophyte species demonstrated the most efficient removal of erythromycin from contaminated waters, and are therefore more indicated for antibiotic phytoremediation projects.


For the very first time, the capacities of floating and submerged plant species used for removing erythromycin from contaminated water were compared. Moreover, plant physiological responses were related to their phytoremediation capacity. Our results promise to have direct impacts on plant and environmental science as well as in toxicology since they will contribute to a better understanding of the effects of antibiotics in plants and indicate species for better performance of phytoremediation programs aiming to reclaim the antibiotic erythromycin.


Assuntos
Araceae , Poluentes Químicos da Água , Antibacterianos , Biodegradação Ambiental , Eritromicina , Plantas , Água , Poluentes Químicos da Água/análise
8.
Ecotoxicol Environ Saf ; 216: 112193, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831726

RESUMO

The increasing use of antibiotics in animal production has become an emergent environmental problem. The large percentages of applied antibiotic doses eliminated in animal excrement often end up contaminating water resources, which are then used for irrigation - compromising agricultural production and/or food security. Here, we evaluated the effects of crop irrigation with water artificially contaminated by enrofloxacin (10 µg l-1) and its accumulation in soybean, bean, and corn tissues. Grain production was evaluated on the basis of grain dry weight plant-1, while enrofloxacin and ciprofloxacin (its breakdown metabolite) concentrations in plant tissues were evaluated by HPLC after harvesting. Diminished production was observed only in soybean plants irrigated with antibiotic-contaminated water. Enrofloxacin [1.68 ng g fresh weight (FW)-1 to 26.17 µg g FW-1] and ciprofloxacin (8.23 ng g FW-1 to 51.05 ng g FW-1), were found in all of the plant tissues (roots, leaves, and seeds) of the three species. Regardless of the species, the highest enrofloxacin concentrations were observed in their roots, followed by the leaves and seeds, while ciprofloxacin concentrations varied among the different plant tissues of the different species. The presence of enrofloxacin in the water used for irrigating soybeans can result in productivity losses and, as that antibiotic was encountered in plant tissues (leaves and seeds) of all of the three species analyzed that are consumed in the diets of both humans and animals, it can interfere with food security.

9.
Malar J ; 19(1): 404, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176792

RESUMO

BACKGROUND: To achieve malaria elimination, it is important to determine the role of human mobility in parasite transmission maintenance. The Alto Juruá basin (Brazil) exhibits one of the largest vivax and falciparum malaria prevalence in the Amazon. The goal of this study was to estimate the contribution of human commutes to malaria persistence in this region, using data from an origin-destination survey. METHODS: Data from an origin-destination survey were used to describe the intensity and motivation for commutations between rural and urban areas in two Alto Juruá basin (Brazil) municipalities, Mâncio Lima and Rodrigues Alves. The relative time-person spent in each locality per household was estimated. A logistic model was developed to estimate the effect of commuting on the probability of contracting malaria for a certain residence zone inhabitant commuting to another zone. RESULTS: The main results suggest that the assessed population is not very mobile. A total of [Formula: see text] households reported spending over [Formula: see text] of their annual person-hour in areas within the same residence zone. Study and work were the most prevalent commuting motivations, calculated at [Formula: see text] and [Formula: see text] respectively. Spending person-hours in urban Rodrigues Alves conferred relative protection to urban Mâncio Lima residents. The opposite effect was observed for those spending time in rural areas of both municipalities. CONCLUSION: Residence area is a stronger determinant for contracting malaria than commuting zones in the Alto Juruá region. As these municipalities are a hotspot for Plasmodium transmission, understanding the main local human fluxes is essential for planning control strategies, since the probability of contracting malaria is dependent on the transmission intensity of both the origin and the displacement area. The natural conditions for the circulation of certain pathogens, such as Plasmodium spp., combined with the Amazon human mobility pattern indicate the need for disease control perspective changes. Therefore, intersectoral public policies should become the basis for health mitigation actions.


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , População Rural/estatística & dados numéricos , Meios de Transporte/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Brasil/epidemiologia , Humanos , Modelos Logísticos , Prevalência
10.
Ecotoxicol Environ Saf ; 203: 111025, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888593

RESUMO

We investigated individual and combined effects of environmentally representative concentrations of amoxicillin (AMX; 2 µg l-1), enrofloxacin (ENR; 2 µg l-1), and oxytetracycline (OXY; 1 µg l-1) on the aquatic macrophyte Lemna minor. While the concentrations of AMX and ENR tested were not toxic, OXY decreased plant growth and cell division. OXY induced hydrogen peroxide (H2O2) accumulation and related oxidative stress through its interference with the activities of mitochondria electron transport chain enzymes, although those deleterious effects could be ameliorated by the presence of AMX and/or ENR, which prevented the overaccumulation of ROS by increasing catalase enzyme activity. L. minor plants accumulated significant quantities of AMX, ENR and OXY from the media, although competitive uptakes were observed when plants were submitted to binary or tertiary mixtures of those antibiotics. Our results therefore indicate L. minor as a candidate for phytoremediation of service waters contaminated by AMX, ENR, and/or OXY.


Assuntos
Amoxicilina/toxicidade , Araceae/efeitos dos fármacos , Enrofloxacina/toxicidade , Oxitetraciclina/toxicidade , Fotossíntese/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Amoxicilina/análise , Amoxicilina/metabolismo , Araceae/crescimento & desenvolvimento , Araceae/metabolismo , Biodegradação Ambiental , Catalase/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Enrofloxacina/análise , Enrofloxacina/metabolismo , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxitetraciclina/análise , Oxitetraciclina/metabolismo , Poluentes Químicos da Água/análise
11.
Ecotoxicol Environ Saf ; 189: 110021, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830604

RESUMO

The failure of the Fundão dam, the largest environmental disaster in the world's mining sector, was responsible for releasing millions of cubic meters of iron ore tailings into the environment. It affected thousands of hectares of the Atlantic Forest domain, one of the biodiversity hotspots for conservation. Considering the urgency to restore the flora of the affected area, we evaluated the effects that iron ore tailings from the Fundão reservoir have on the germination and initial growth of tree species native to the Atlantic Forest in the Rio Doce basin. We demonstrated that the tailings do not affect the seed germination, but do negatively interfere with plant growth. Lower biomass production, height, leaf area, chlorophyll concentration and photosynthesis as well as high concentration of iron was observed in plants grown in the tailings. Thus, we investigated if these deleterious effects were due to the presence of potentially toxic metals or nutritional deficiency imposed by low fertility of the tailings. We concluded that reduced growth was a result of nutritional limitations due to low nutrient availability, low organic matter content and low cation exchange capacity of the tailings. This conclusion was further supported by the application of fertilization, which reversed the deleterious effect of the waste on the growth of plants, assuring physiological levels of iron and nutrients in the shoot. Thus, this strategy should be considered for in situ recovery projects aiming to improve the performance of native plants.


Assuntos
Solo/química , Árvores/crescimento & desenvolvimento , Biomassa , Recuperação e Remediação Ambiental , Fertilização , Ferro/análise , Ferro/metabolismo , Mineração , Nutrientes/análise , Nutrientes/deficiência , Nutrientes/metabolismo , Floresta Úmida , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Árvores/classificação , Árvores/metabolismo
12.
Ecotoxicol Environ Saf ; 196: 110549, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251953

RESUMO

Chemicals used to assure agricultural production and the feasibility of planting sites often end up in bodies of water used for crop irrigation. In a pot study, we investigated the consequences associated with the irrigation of maize with water contaminated by ciprofloxacin (Cipro; 0, 0.2, 0.8, 1.4 and 2.0 µg l-1) and/or glyphosate (0, 5, 25 and 50 mg l-1) on yields and food safety. Glyphosate in concentrations ≥25 mg l-1 prevented plant establishment, regardless of Cipro presence. Evaluations made at the V5 stage of plants reveal that Cipro concentrations ≥0.8 µg l-1 and glyphosate decreased photosynthesis and induced changes in leaf anatomy and stem biophysical properties that may contribute to decreased kernel yields. When those chemicals were applied together, kernel yield reductions were accentuated, evidencing their interactive effects. Irrigation with contaminated water resulted in accumulations of Cipro and glyphosate (as well as its metabolite, aminomethylphosphonic acid) in plant tissues. Accumulation of these chemicals in plant tissues such as leaves and kernels is a problem, since they are used to feed animals and humans. Moreover, these chemicals are of potential toxicological concern, principally due to residue accumulations in the food chain. Specially, the antibiotic residue accumulations in maize tissues can assist the induction of antibiotic resistance in dangerous bacteria. Therefore, we point out the urgency of monitoring the quality of water used for crop irrigation to avoid economic and food-quality losses.


Assuntos
Antibacterianos/toxicidade , Ciprofloxacina/toxicidade , Glicina/análogos & derivados , Poluentes Químicos da Água/toxicidade , Zea mays/efeitos dos fármacos , Irrigação Agrícola , Animais , Antibacterianos/farmacocinética , Ciprofloxacina/farmacocinética , Produtos Agrícolas/anatomia & histologia , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/economia , Inocuidade dos Alimentos , Glicina/farmacocinética , Glicina/toxicidade , Humanos , Fotossíntese/efeitos dos fármacos , Folhas de Planta/anatomia & histologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Poluentes Químicos da Água/farmacocinética , Zea mays/anatomia & histologia , Zea mays/metabolismo , Glifosato
13.
Int J Phytoremediation ; 22(13): 1362-1371, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32672473

RESUMO

The synergistic relationship between arbuscular mycorrhizal fungi and plant species may play a key role in phytoremediation of arsenic(As)-contaminated soils. By using modified Leonard jars, we investigated both the distinct and integrative roles of arbuscular mycorrhizal fungi (AMF-Acaulospora scrobiculata) and rhizobia (BH-ICB-A8) isolated from As-contaminated soil on the capacity of Anadenanthera peregrina to reclaim arsenate [As(V)] from soil. AMF inoculation greatly increased plant phosphorous nutrition, as reflected in greater growth, and increased As-concentrations in the roots and shoots. While rhizobia inoculation alone increased nitrogen nutrition it did not promote plant growth or As-uptake. Rhizobia and AMF inoculation together had synergistic effects, however, increasing both the growth and the As-phytoremediation capacity of A. peregrina. Joint inoculation with rhizobia and AMF should therefore be considered a potential technique for rehabilitating As-contaminated areas using A. peregrina.


Assuntos
Fabaceae , Micorrizas , Rhizobium , Poluentes do Solo , Biodegradação Ambiental , Raízes de Plantas/química , Solo , Poluentes do Solo/análise
14.
Cutan Ocul Toxicol ; 39(2): 126-133, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32183539

RESUMO

Background: ultraviolet radiation types A and B (UV) (400-315nm and 315-280nm respectively) are the main components present in sunlight known to cause skin injuries. Arnica montana is a plant that has been widely studied for containing anti-inflammatory, healing and analgesic properties capable of preventing or ameliorating lesions. Here, we investigated the therapeutic effect of topical application of Arnica montana after UVB-induced cutaneous injuries in mice.Methods: mice were exposed to UVB radiation (Philips TL40W/12 RS lamp) in a period of 3 hours. After one hour of radiation exposure, the animals were treated with topical application of Arnica montana ointment (250 mg/g) in the ear. At the time of 16 hours after treatment, the parameters of edema, oxidative stress and inflammatory reaction were measured in the ear of mice.Results: our results demonstrated that topical treatment with Arnica montana reduced the UVB-induced inflammatory response as demonstrated by the reduction of ear edema, inhibition of myeloperoxidase activation, decrease of nuclear factor kappa B levels and reduction of proinflammatory cytokines levels, such as interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and interferon-gamma. In addition, Arnica montana ameliorated oxidative damage mediated by UVB radiation, as demonstrated by the reduction of lipid peroxidation, protein oxidation and increase of tissue antioxidant capacity and glutathione levels in the ear.Conclusion: we concluded that Arnica montana ointment is effective in alleviating the auricular inflammatory process and oxidative damage induced by acute UVB radiation, sustaining the traditional use of Arnica montana for the treatment of skin disorders.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Arnica , Edema/tratamento farmacológico , Transtornos de Fotossensibilidade/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Lesões Experimentais por Radiação/tratamento farmacológico , Raios Ultravioleta/efeitos adversos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Edema/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Pomadas , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Transtornos de Fotossensibilidade/metabolismo , Preparações de Plantas/farmacologia , Lesões Experimentais por Radiação/metabolismo
15.
Arch Biochem Biophys ; 663: 173-182, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30639329

RESUMO

Muscle wasting or atrophy is extensively associated with human systemic diseases including diabetes, cancer, and kidney failure. Accumulating evidence from transcriptional profiles has noted that a common set of genes, termed atrogenes, is modulated in atrophying muscles. However, the transcriptional changes that trigger the reversion or attenuation of muscle atrophy have not been characterized at the molecular level until now. Here, we applied cDNA microarrays to investigate the transcriptional response of androgen-sensitive Levator ani muscle (LA) during atrophy reversion. Most of the differentially expressed genes behaved as atrogenes and responded to castration-induced atrophy. However, seven genes (APLN, DUSP5, IGF1, PIK3IP1, KLHL38, PI15, and MKL1) did not respond to castration but instead responded exclusively to testosterone replacement. Considering that almost all proteins encoded by these genes are associated with the reversion of atrophy and may function as regulators of cell proliferation/growth, our results provide new perspectives on the existence of anti-atrogenes.


Assuntos
Androgênios/metabolismo , Perfilação da Expressão Gênica , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Animais , Jejum , Terapia de Reposição Hormonal , Masculino , Camundongos , Modelos Biológicos , Músculo Esquelético/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Orquiectomia , Ratos , Ratos Wistar , Testosterona/administração & dosagem
16.
Neurochem Res ; 44(9): 2202-2214, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31422521

RESUMO

Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose-response to MMA (1-10 mM), MA (1-10 mM) and IP (63-500 µM) was performed. Thereafter, flies were concomitantly exposed to MA (5 mM), MMA (5 mM) and/or IP (250 µg/mL) during 15 days for survival assay, and for 48 hs to MA (1 or 5 mM), MMA (1 or 5 mM) and/or IP (250 µg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.


Assuntos
Antioxidantes/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Ilex paraguariensis/química , Malonatos/toxicidade , Extratos Vegetais/farmacologia , Animais , Feminino , Locomoção/efeitos dos fármacos , Masculino , Compostos de Sulfidrila/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
17.
Stat Med ; 38(22): 4363-4377, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31292995

RESUMO

One difficulty for real-time tracking of epidemics is related to reporting delay. The reporting delay may be due to laboratory confirmation, logistical problems, infrastructure difficulties, and so on. The ability to correct the available information as quickly as possible is crucial, in terms of decision making such as issuing warnings to the public and local authorities. A Bayesian hierarchical modelling approach is proposed as a flexible way of correcting the reporting delays and to quantify the associated uncertainty. Implementation of the model is fast due to the use of the integrated nested Laplace approximation. The approach is illustrated on dengue fever incidence data in Rio de Janeiro, and severe acute respiratory infection data in the state of Paraná, Brazil.


Assuntos
Teorema de Bayes , Vigilância em Saúde Pública/métodos , Simulação por Computador , Epidemias , Humanos
18.
Am J Primatol ; 81(6): e23000, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31192493

RESUMO

Howler monkey capture is an arduous and expensive task requiring trained and specialized professionals. We compared strategies and methods to most efficiently capture Alouatta guariba clamitans in remnants of the Atlantic Forest in Rio de Janeiro and its bordering states of Minas Gerais and São Paulo. We tested whether or not the success of expeditions in the forest with anesthetic darts, nets, and baited traps differed with and without the support of an information network, a contact chain built with key institutions and inhabitants to continuously monitor howler monkey presence. The influence of forest conditions (vegetation type and fragment size) upon darting success was also evaluated. We captured 24 free-living A. guariba clamitans. No howler monkey was caught with traps, probably due to the predominantly folivore feeding to high local plant diversity providing a great variety of food options. Captures based on an information network were significantly more efficient in terms of numbers of caught monkeys than without it. Captures with darts were considerably more efficient when performed in semideciduous forests and small forest fragments as opposed to ombrophilous forests or large woods. Although we walked great distances within the forest searching for howler monkeys, all but one animal were captured at the forest fringes. Hindrances to search and the darting method in the Atlantic Forest, for example, the steep terrain, high tree canopies, hunt pressure, and low A. guariba clamitans population density, were mitigated with the use of the information network in this monkey capture. Moreover, the information network enhanced the surveillance of zoonotic diseases, which howler monkeys and other nonhuman primates are reservoirs in Brazil, such as malaria and yellow fever.


Assuntos
Alouatta/fisiologia , Imobilização/veterinária , Alouatta/parasitologia , Alouatta/virologia , Anestésicos/administração & dosagem , Animais , Brasil/epidemiologia , Florestas , Imobilização/métodos , Malária/epidemiologia , Doenças dos Macacos/epidemiologia , Febre Amarela/epidemiologia
19.
Pathophysiology ; 26(2): 137-143, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31040041

RESUMO

Some studies have showed that intake of blackberry juice (BBJ) can prevent urinary tract infections. However, there is a lack of studies that evaluate the mechanisms by which BBJ has protective effect. Thus, the aim of current study was to evaluate the effects of BBJ supplementation on cisplatin-induced renal pathophysiology in mice. Mice were supplemented with BBJ (10 mL/kg) for seven days. One hour after the last supplementation with BBJ, mice received cisplatin (10 mg/kg, i.p.). Seventy-two hours after cisplatin administration, blood was collected and biochemical analysis were performed (urea and creatinine), kidney was dissected and utilized in histological and oxidative evaluations. Cisplatin caused severe injury in renal tissue, in markers of renal damage (urea and creatinine) generated increased of plasmatic levels. Besides that, the cisplatin induced decreased of enzymes activities in renal tissue (superoxide dismutase, glutathione S-transferase and catalase). In contrast, BBJ supplementation protected against histopathological alterations through decreased in urea and creatinine levels and modulation of catalase enzyme activity. Thus, BBJ supplementation protected the renal system of mice from deleterious effects. We suggest that high concentrations of Cyanidin 3-O-glucoside and Cyanidin 3-O-rutinoside are responsible for antioxidant role of BBJ supplementation in renal pathophysiology induced by cisplatin exposure. Also, these results reinforcing the importance of including BBJ in the human diet aimed at preventing renal diseases.

20.
Mol Cell Neurosci ; 88: 93-106, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29369791

RESUMO

An increasing body of evidence indicates that the activation of indoleamine-2,3-dyoxigenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is involved in Aß1-42-neurotoxicity and AD pathogenesis. We have reported for the first time that brain IDO activation is related to Aß1-42 exposure in young mice. Because aging is characterized by a brain dyshomeostasis and because it remains the most dominant risk factor for AD, the purpose of this study was to determine whether aging is associated with a higher sensitivity to behavioural and neurochemical alterations elicited by an intracerebroventricular (i.c.v.) injection of Aß1-42 (400 pmol/mice), and whether KYN pathway is involved in these effects. We confirmed that aged mice displayed higher cognitive deficit in the object recognition test and higher anxiety-like behaviour in the elevated plus-maze and open field tests after the Aß1-42 administration. Aged mice also responded to Aß1-42 with a higher deficiency of brain-derived neurotrophic factor, glutathione levels and total radical-trapping antioxidant capacity, a higher IDO activity, and a higher KYN and KYN/tryptophan ratio in the prefrontal cortex and hippocampus. These effects of Aß1-42 were associated with a higher proinflammatory status, as measured by higher levels of interleukin-6, lower levels of interleukin-10 and higher expression of glial fibrillary acidic protein (GFAP) and allograft inflammatory factor 1 (Iba1) in the brain of aged mice. These results represent primary evidence suggesting that age-associated inflammatory signature and down-regulation of neuroprotectants in the brain render aged mice more vulnerable to Aß1-42-induced memory loss, anxiety symptoms and KYN pathway dysregulation.


Assuntos
Envelhecimento/fisiologia , Peptídeos beta-Amiloides/metabolismo , Ansiedade/fisiopatologia , Cognição/fisiologia , Transtornos da Memória/fisiopatologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/metabolismo , Córtex Pré-Frontal/metabolismo
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