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1.
Cell ; 187(4): 814-830.e23, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38364788

ABSTRACT

Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show that RNLTR12-int-encoded RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int-like sequences (which we name RetroMyelin) are found in all jawed vertebrates, and we further demonstrate their function in regulating myelination in two different vertebrate classes (zebrafish and frogs). Our study therefore suggests that retroviral endogenization played a prominent role in the emergence of vertebrate myelin.


Subject(s)
Myelin Sheath , Retroelements , Animals , Gene Expression , Myelin Sheath/metabolism , Oligodendroglia/metabolism , Retroelements/genetics , RNA/metabolism , Zebrafish/genetics , Anura
2.
Development ; 150(12)2023 06 15.
Article in English | MEDLINE | ID: mdl-37309812

ABSTRACT

Targeted knock-in of fluorescent reporters enables powerful gene and protein analyses in a physiological context. However, precise integration of long sequences remains challenging in vivo. Here, we demonstrate cloning-free and precise reporter knock-in into zebrafish genes, using PCR-generated templates for homology-directed repair with short homology arms (PCR tagging). Our novel knock-in reporter lines of vesicle-associated membrane protein (vamp) zebrafish homologues reveal subcellular complexity in this protein family. Our approach enables fast and efficient reporter integration in the zebrafish genome (in 10-40% of injected embryos) and rapid generation of stable germline-transmitting lines.


Subject(s)
CRISPR-Cas Systems , Zebrafish , Animals , CRISPR-Cas Systems/genetics , Zebrafish/genetics , Gene Knock-In Techniques , Genome , Gene Editing
3.
Chem Biodivers ; : e202400679, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822223

ABSTRACT

Banisteriopsis (Malpighiaceae) is an important genus of neotropical savannas with related biological and medicinal activities but under-explored metabolomic profiles. We present a chemometric analysis for discriminating secondary metabolites of three species of Banisteriopsis (B. laevifolia, B. malifolia, and B. stellaris) leaves. Initially, each species was separately extracted with ethanol:water (4:1, v/v) and analysed by Ultra Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS/MS). The chromatographic profiles were subjected to Global Natural Product Social (GNPS) and Partial Least Squares Discriminant Analysis (PLS-DA). Eighty-nine compounds (cosine ≥ 0.90) were annotated, including flavonoids, phenolics, and acids. The chemometric analysis (VIP Score) showed each species' relative concentration of the more relevant compounds. In addition, four compounds that discriminate the metabolomic profiles of B. laevifolia, B. malifolia, and B. stellaris were identified by PLS-DA.

4.
Molecules ; 29(12)2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38930806

ABSTRACT

Pterocaulon polystachyum is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of non-volatile extracts may be related to the presence of coumarins, a promising group of secondary metabolites. In the present study, leaves and inflorescences previously used for the extraction of essential oils instead of being disposed of were subjected to extraction with supercritical CO2 after pretreatment with microwaves. An experimental design was followed to seek the best extraction condition with the objective function being the maximum total extract. Pressure and temperature were statistically significant factors, and the optimal extraction condition was 240 bar, 60 °C, and pretreatment at 30 °C. The applied mathematical models showed good adherence to the experimental data. The extracts obtained by supercritical CO2 were analyzed and the presence of coumarins was confirmed. The extract investigated for cytotoxicity against bladder tumor cells (T24) exhibited significant reduction in cell viability at concentrations between 6 and 12 µg/mL. The introduction of green technology, supercritical extraction, in the exploration of P. polystachyum as a source of coumarins represents a paradigm shift with regard to previous studies carried out with this species, which used organic solvents. Furthermore, the concept of circular bioeconomy was applied, i.e., the raw material used was the residue of a steam-distillation process. Therefore, the approach used here is in line with the sustainable exploitation of native plants to obtain extracts rich in coumarins with cytotoxic potential against cancer cells.


Subject(s)
Carbon Dioxide , Chromatography, Supercritical Fluid , Coumarins , Plant Extracts , Coumarins/chemistry , Coumarins/isolation & purification , Coumarins/pharmacology , Carbon Dioxide/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Humans , Chromatography, Supercritical Fluid/methods , Plant Components, Aerial/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification
5.
Proteomics ; 23(16): e2200230, 2023 08.
Article in English | MEDLINE | ID: mdl-37183273

ABSTRACT

Post-translational methylation of proteins, which occurs in arginines and lysines, modulates several biological processes at different levels of cell signaling. Recently, methylation has been demonstrated in the regulation beyond histones, for example, in the dynamics of protein-protein and protein-nucleic acid interactions. However, the presence and role of non-histone methylation in Trypanosoma cruzi, the etiologic agent of Chagas disease, has not yet been elucidated. Here, we applied mass spectrometry-based-proteomics (LC-MS/MS) to profile the methylproteome of T. cruzi epimastigotes, describing a total of 1252 methyl sites in 824 proteins. Functional enrichment and protein-protein interaction analysis show that protein methylation impacts important biological processes of the parasite, such as translation, RNA and DNA binding, amino acid, and carbohydrate metabolism. In addition, 171 of the methylated proteins were previously reported to bear phosphorylation sites in T. cruzi, including flagellar proteins and RNA binding proteins, indicating that there may be an interplay between these different modifications in non-histone proteins. Our results show that a broad spectrum of functions is affected by methylation in T. cruzi, indicating its potential to impact important processes in the biology of the parasite and other trypanosomes.


Subject(s)
Histones , Trypanosoma cruzi , Histones/metabolism , Trypanosoma cruzi/chemistry , Trypanosoma cruzi/genetics , Methylation , Chromatography, Liquid , Tandem Mass Spectrometry , Protozoan Proteins/genetics
6.
J Evol Biol ; 36(11): 1595-1608, 2023 11.
Article in English | MEDLINE | ID: mdl-37885128

ABSTRACT

Hybridization could be considered part of the evolutionary history of many species. The hybridization among sea turtle species on the Brazilian coast is atypical and occurs where nesting areas and reproductive seasons overlap. Integrated analysis of morphology and genetics is still scarce, and there is no evidence of the parental chromosome set distribution in sea turtle interspecific hybrids. In this study, chromosome markers previously established for pure sea turtle species were combined with morphological and molecular analyses aiming to recognize genetic composition and chromosome sets in possible interspecific hybrids initially identified by mixed morphology. The data showed that one hybrid could be an F2 individual among Caretta caretta × Eretmochelys imbricata × Chelonia mydas, and another is resulting from backcross between C. caretta × Lepidochelys olivacea. Native alleles of different parental lineages were reported in the hybrids, and, despite this, it was verified that the hybrid chromosome sets were still balanced. Thus, how sea turtle hybridism can affect genetic features in the long term is a concern, as the implications of the crossing-over in hybrid chromosomal sets and the effects on genetic function are still unpredictable.


Subject(s)
Turtles , Animals , Turtles/genetics , Biological Evolution , Reproduction , Chromosomes , Cytogenetic Analysis
7.
J Nucl Cardiol ; 30(6): 2327-2337, 2023 12.
Article in English | MEDLINE | ID: mdl-37165114

ABSTRACT

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.


Subject(s)
Chagas Cardiomyopathy , Chagas Disease , Pentoxifylline , Cricetinae , Animals , Female , Chagas Cardiomyopathy/diagnostic imaging , Pentoxifylline/pharmacology , Pentoxifylline/therapeutic use , Stroke Volume , Ventricular Function, Left , Tomography, X-Ray Computed , Inflammation , Perfusion
8.
Phys Chem Chem Phys ; 25(48): 32922-32930, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38018412

ABSTRACT

This work delves into the bonding nature of the pentagonal-pyramidal benzene and hexamethylbenzene dications, C6R62+ (R = H and CH3), which contain a hexacoordinate carbon. The study employs a range of methodologies to analyze a series of scalar fields, including electron density, electron localization function, local momentum representation, and the evaluation of the Coulomb hole through information theory-derived functions. The findings unveil that electron density undergoes transfer from the pentagonal ring to the apical group. As a result, the base of the complex accumulates the positive charge. Moreover, an extended electron density domain emerges between the carbon pentagon and the apical carbon atom. This phenomenon is related to the molecular orbitals with a dipolar character aligned with the principal axis of the molecule. The results also indicate an electron density polarization towards the apical carbon, coupled with an exclusion of electron density surrounding both the apical carbon and the lower portion of the pentagonal ring. These provide valuable insights into the complex bonding nature of hexacoordinate carbon and its implications for organic chemistry.

9.
J Nat Prod ; 86(3): 621-632, 2023 03 24.
Article in English | MEDLINE | ID: mdl-36848642

ABSTRACT

The Aedes aegypti (Diptera: Culicidae) mosquito is the vector of several arboviruses in tropical and subtropical areas of the globe, and synthetic pesticides remain the most widely used combat strategy. This study describes the investigation of secondary metabolites with larvicidal activity from the Malpighiaceae taxon using a metabolomic and bioactivity-based approach. The workflow initially consisted of a larvicidal screening of 394 extracts from the leaves of 197 Malpighiaceae samples, which were extracted using solvents of different polarity, leading to the selection of Heteropterys umbellata for the identification of active compounds. By employing untargeted mass spectrometry-based metabolomics and multivariate analyses (PCA and PLS-DA), it was possible to determine that the metabolic profiles of different plant organs and collection sites differed significantly. A bioguided approach led to the isolation of isochlorogenic acid A (1) and the nitropropanoyl glucosides karakin (2) and 1,2,3,6-tetrakis-O-[3-nitropropanoyl]-beta-glucopyranose (3). These nitro compounds exhibited larvicidal activity, possibly potentialized by synergistic effects of their isomers in chromatographic fractions. Additionally, targeted quantification of the isolated compounds in different extracts corroborated the untargeted results from the statistical analyses. These results support a metabolomic-guided approach in combination with classical phytochemical techniques to search for natural larvicidal compounds for arboviral vector control.


Subject(s)
Aedes , Insecticides , Animals , Plant Extracts/chemistry , Insecticides/chemistry , Glycosides/pharmacology , Glycosides/analysis , Larva , Mosquito Vectors , Plant Leaves/chemistry , Mass Spectrometry , Metabolomics
11.
Int J Mol Sci ; 24(6)2023 Mar 09.
Article in English | MEDLINE | ID: mdl-36982342

ABSTRACT

QTAIM and source function analysis were used to explore the non-covalent bonding in twelve different water clusters (H2O)n obtained by considering n = 2-7 and various geometrical arrangements. A total of seventy-seven O-H⋯O hydrogen bonds (HBs) were identified in the systems under consideration, and the examination of the electron density at the bond critical point (BCP) of these HBs revealed the existence of a great diversity of O-H⋯O interactions. Furthermore, the analysis of quantities, such as |V(r)|/G(r) and H(r), allowed a further description of the nature of analogous O-H⋯O interactions within each cluster. In the case of 2-D cyclic clusters, the HBs are nearly equivalent between them. However, significant differences among the O-H⋯O interactions were observed in 3-D clusters. The assessment of the source function (SF) confirmed these findings. Finally, the ability of SF to decompose the electron density (ρ) into atomic contributions allowed the evaluation of the localized or delocalized character of these contributions to ρ at the BCP associated to the different HBs, revealing that weak O-H⋯O interactions have a significant spread of the atomic contributions, whereas strong interactions have more localized atomic contributions. These observations suggest that the nature of the O-H⋯O hydrogen bond in water clusters is determined by the inductive effects originated by the different spatial arrangements of the water molecules in the studied clusters.

12.
Ecotoxicology ; 31(1): 161-167, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34773559

ABSTRACT

Caffeine is a contaminant frequently detected in water bodies. Growth trends in both human population and caffeine consumption per capita are expected to exacerbate the occurrence of caffeine in freshwaters. Yet the effects of caffeine on native fish fauna are poorly understood. We exposed larvae of an endemic Neotropical catfish (Rhamdia quelen) to a range of caffeine concentrations for 30 days. We found that larvae exposed to the highest concentration (16 mg L-1) showed skeletal deformations and reduced growth. We further compiled measured environmental concentrations of caffeine in surface freshwater globally and performed a risk assessment. Our analysis points to a low risk to R. quelen and equally sensitive fish species in ~90% of the freshwater ecosystems considered in our analysis. The risk quotient is higher in freshwater ecosystems of South and Central America, where R. quelen is endemic. Although the ecotoxicological risk is currently low in most places, increased caffeine consumption, exacerbated by the lack of sanitation, is expected to increase caffeine concentrations in many parts of the world, posing a threat of sublethal morphological effects to local fish species.


Subject(s)
Catfishes , Water Pollutants, Chemical , Animals , Caffeine/toxicity , Ecosystem , Fresh Water , Humans , Water Pollutants, Chemical/toxicity
13.
Molecules ; 27(3)2022 Jan 31.
Article in English | MEDLINE | ID: mdl-35164235

ABSTRACT

A widely disseminated native species from Australia, Acacia mearnsii, which is mainly cultivated in Brazil and South Africa, represents a rich source of natural tannins used in the tanning process. Many flowers of the Acacia species are used as sources of compounds of interest for the cosmetic industry, such as phenolic compounds. In this study, supercritical fluid extraction was used to obtain non-volatile compounds from A. mearnsii flowers for the first time. The extract showed antimicrobial activity and the presence of p-anisic acid, a substance with industrial and pharmaceutical applications. The fractionation of the extract was performed using a chromatographic column and the fraction containing p-anisic acid presented better minimum inhibitory concentration (MIC) results than the crude extract. Thus, the extraction process was optimized to maximize the p-anisic acid extraction. The response surface methodology and the Box-Behnken design was used to evaluate the pressure, temperature, the cosolvent, and the influence of the particle size on the extraction process. After the optimization process, the p-anisic acid yield was 2.51% w/w and the extraction curve was plotted as a function of time. The simulation of the extraction process was performed using the three models available in the literature.


Subject(s)
Acacia/chemistry , Bacteria/drug effects , Carbon Dioxide/chemistry , Chromatography, Supercritical Fluid/standards , Ethanol/chemistry , Hydroxybenzoate Ethers/pharmacology , Plant Extracts/pharmacology , Antioxidants/isolation & purification , Antioxidants/pharmacology , Flowers/chemistry , Hydroxybenzoate Ethers/isolation & purification , Models, Theoretical , Plant Extracts/isolation & purification
14.
J Clin Immunol ; 41(5): 1048-1063, 2021 07.
Article in English | MEDLINE | ID: mdl-33660144

ABSTRACT

Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy. METHODS: We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY. RESULTS: We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related - most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-γ on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (ΔψM), indicating mitochondrial dysfunction. CONCLUSION: Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-γ-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.


Subject(s)
Chagas Cardiomyopathy/genetics , Inflammation/genetics , Mitochondria/genetics , Adult , Aged , Aged, 80 and over , Female , Genetic Predisposition to Disease , Genetic Variation , Humans , Male , Middle Aged , Exome Sequencing
15.
Int J Equity Health ; 20(1): 197, 2021 08 30.
Article in English | MEDLINE | ID: mdl-34461895

ABSTRACT

BACKGROUND: Most estimates of visual impairment and blindness worldwide do not include data from specific minority groups as indigenous populations. We aimed to evaluate frequencies and causes of visual impairment and blindness in a large population sample from the Xingu Indigenous Park. METHODS: Cross-sectional study performed at Xingu Indigenous Park, Brazil, from 2016 to 2017. Residents from 16 selected villages were invited to participate and underwent a detailed ocular examination, including uncorrected (UVA) and best-corrected visual acuity (BCVA). The main cause of UVA < 20/32 per eye was determined. RESULTS: A total of 2,099 individuals were evaluated. Overall, the frequency of visual impairment and blindness was 10.00% (95% CI: 8.72-11.29%) when considering UVA, decreasing to 7.15% (95% CI: 6.04-8.25%) when considering BCVA. For each increasing year on age, the risk  of being in the visually impaired or blind category increased by 9% (p < 0.001). Cataracts (39.1%) and uncorrected refractive errors (29.1%) were the most frequent causes of visual impairment and blindness in this population. The main causes among those aged 45 years and more were cataracts (54.5%) while refractive errors were the main cause in adults aged 18 to 45 years (50.0%) and children up to 18 years old (37.1%). CONCLUSIONS: A higher frequency of visual impairment and blindness was observed in the indigenous population when compared to worldwide estimates with most of the causes being preventable and/or treatable. Blindness prevention programs should focus on accessibility to eye exam, cataract surgeries and eyeglass distribution.


Subject(s)
Blindness , Vision, Low , Adolescent , Adult , Blindness/epidemiology , Blindness/etiology , Brazil/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Health Status Disparities , Humans , Infant , Infant, Newborn , Middle Aged , Population Groups/statistics & numerical data , Prevalence , Vision, Low/epidemiology , Vision, Low/etiology , Young Adult
16.
Int J Cosmet Sci ; 43(2): 225-234, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33452685

ABSTRACT

OBJECTIVE: This study aims to correlate new experimental data relevant to the description of the combined evaporation/permeation process of a perfume applied onto the skin. METHODS: The vapour pressure data were measured by thermogravimetric analysis (TG-DTA). The Antoine constants and the Clarke and Glew parameters were determined for the same set of fragrance molecules to describe its low vapour pressures at new temperature ranges. The permeability coefficient of a set of 14 fragrance molecules in ethanolic solution was determined by Franz diffusion cell experiments, using porcine skin. The samples were analysed by gas chromatography with a flame ionization detector (GC/FID) and high-performance liquid chromatography with UV visible detector (HPLC/UV). A QSAR model was proposed to correlate the experimental data. RESULTS: The Antoine constants were determined and presented low standard deviations. The Clarke and Glew physically significant parameters were obtained along with its statistical analysis. The fitting is good since the magnitude order is in accordance with the literature, associated with the low correlation between the estimated parameters and low standard deviations. The presented correlation, based on a mixture using only ethanol as solvent, showed better results than previous QSAR models with a standard relative deviation ( σ r ) of 0.190, a standard error (SE) of 0.397 and a determination coefficient (R2 ) of 0.7786. CONCLUSION: The dataset is still small compared to larger and more general QSAR models; however, it is much more specific as to the type of solvent and class of materials studied. This work represents an advance for the modelling of the perfume diffusion process since it specifies important properties that until then had been treated in a more general way.


OBJECTIF: Cette étude vise à corréler de nouvelles données expérimentales pertinentes à la description du processus combiné d'évaporation/perméation d'un parfum appliqué sur la peau. MÉTHODES: Les données de pression de vapeur ont été mesurées par analyse thermogravimétrique (TG-DTA). Les constantes d'Antoine et les paramètres de Clarke & Glew ont été déterminés pour le même ensemble de molécules de parfum afin de décrire ses faibles pressions de vapeur à de nouvelles plages de température. Le coefficient de perméabilité d'un ensemble de 14 molécules de parfum en solution éthanolique a été déterminé par des expériences de cellules de diffusion de Franz, en utilisant de la peau de porc. Les échantillons ont été analysés par chromatographie en phase gazeuse avec un détecteur à ionisation de flamme (GC / FID) et chromatographie liquide haute performance avec détecteur UV visible (HPLC / UV). Un modèle QSAR a été proposé pour corréler les données expérimentales. RÉSULTATS: Les constantes d'Antoine ont été déterminées et ont présenté de faibles écarts types. Les paramètres physiquement significatifs de Clarke & Glew ont été obtenus avec son analyse statistique. L'ajustement est bon car l'ordre de grandeur est conforme à la littérature, associé à la faible corrélation entre les paramètres estimés et les faibles écarts types. La corrélation présentée, basée sur un mélange utilisant uniquement de l'éthanol comme solvant, a montré de meilleurs résultats que les modèles QSAR précédents avec un écart relatif standard (σr) de 0,190, une erreur standard (SE) de 0,397 et un coefficient de détermination (R2) de 0,7786. CONCLUSION: L'ensemble de données est encore petit par rapport aux modèles QSAR plus grands et plus généraux ; cependant, il est beaucoup plus spécifique quant au type de solvant et à la classe de matériaux étudiés. Ce travail représente une avancée pour la modélisation du processus de diffusion des parfums car il précise des propriétés importantes jusque-là traitées de manière plus générale.


Subject(s)
Odorants , Permeability , Gas Chromatography-Mass Spectrometry/methods , Thermogravimetry
17.
Homeopathy ; 110(4): 256-262, 2021 11.
Article in English | MEDLINE | ID: mdl-33946121

ABSTRACT

BACKGROUND: Nosodes are homeopathic preparations (HPs) obtained from tissues or substances associated with the targeted disease or from culture of the pathogenic agent. Nosodes are thought to modulate host resistance, easing symptoms or promoting cure. A few studies have been published about control of plant-parasitic nematodes with HPs, but none with nosodes. Conceptually, nosodes prepared from nematode infective stages might interact with the plant's pathogen-recognition system and initiate or modulate plant resistance to nematodes. OBJECTIVE: Our goal was to investigate whether nosodes prepared from second-stage juveniles (J2) of Meloidogyne enterolobii can affect the moderate resistance already existing in the lettuce cultivar 'Elisa'. METHODS: Nosodes at the Hahnemannian concentrations (cH) 6, 18, 30 and 42 were applied on lettuce plants through irrigation, with a constant daily dosage. The nosode treatment started at the seedling stage, before nematode inoculation with 3,000 eggs + J2 per plant. A series of absolute and relative controls, and 10 replicates per treatment, were employed. At harvest, variables related to plant growth and nematode reproduction were assessed. RESULTS: The nosode at 6, 18, and 30cH reduced (p <0.05) the nematode reproduction factor and root density. The nosode effect was cH-dependent since nematode reproduction was favored by treatment with 42cH. The nosode also affected (p <0.05) lettuce roots, which presented higher or lower fresh weight and volume depending on the cH applied and the condition-parasitized or not. CONCLUSION: Nosodes obtained from Meloidogyne J2 may affect plant parasitism by nematodes, possibly by interfering with plant resistance. The nature-positive or negative-and intensity of the nosode effect depends on the cH applied to the plants. Further studies are necessary to identify which cH values are more effective in reducing nematode reproduction without causing negative side effects on plant growth.


Subject(s)
Homeopathy , Materia Medica , Tylenchoidea , Animals , Lactuca
18.
Br J Cancer ; 123(4): 534-541, 2020 08.
Article in English | MEDLINE | ID: mdl-32499569

ABSTRACT

BACKGROUND: Host-microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear. METHODS: We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice. RESULTS: We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-ß gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice. CONCLUSIONS: Host-microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells.


Subject(s)
Anti-Bacterial Agents/adverse effects , Dysbiosis/immunology , Germ-Free Life , Interleukin-9/metabolism , Melanoma/microbiology , T-Lymphocytes/immunology , Animals , Cell Differentiation , Cell Line, Tumor , Dysbiosis/chemically induced , Dysbiosis/therapy , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Interleukin-4/metabolism , Male , Melanoma/immunology , Mice , Mucous Membrane/drug effects , Mucous Membrane/immunology , Neoplasm Transplantation , T-Lymphocytes/drug effects , Transforming Growth Factor beta/metabolism , Tumor Microenvironment
19.
Microb Pathog ; 142: 104063, 2020 Feb 24.
Article in English | MEDLINE | ID: mdl-32061821

ABSTRACT

Dental caries is a multifactorial chronic-infection disease, which starts with a bacterial biofilm formation caused mainly by Streptococcus mutans. The use of probiotics has shown numerous health benefits, including in the fight against oral diseases. Strains of Lactobacillus fermentum have already shown probiotic potential against S. mutans, but there are still few studies. Thus, the aim of our study was to evaluate the antimicrobial activity of the inoculum and metabolites produced by L. fermentum TcUESC01 against S. mutans UA159. For this, a growth curve of L. fermentum was performed and both the inoculum and the metabolites formed in the fermentation were tested against the growth of S. mutans UA159 in agar diffusion tests, and only its metabolites were tested to determine the minimum inhibitory concentration, minimal bactericidal concentration and inhibition of cell adhesion. Inhibition of biofilm formation, pH drop and proton permeability were also tested with the metabolites. The zone of inhibition began to be formed at 14 h and continued until 16 h. The inoculum containing L. fermentum also showed zone of inhibition. The MIC for the metabolites was 1280 mg/mL and the MBC was obtained with a concentration higher than the MIC equal to 5120 mg/mL. Half of the MIC concentration (640 mg/mL) was required to inhibit S. mutans adhesion to the surface of the microplates. In the biofilm analyzes, the treatment with the metabolites in the tested concentration was not able to reduce biomass, insoluble glucans and alkali soluble compared to the control biofilm (p > 0.05). The metabolites also did not affect acid production and acid tolerance of S. mutans cells in biofilms compared to saline group (p > 0.05). Lactic acid (50.38%) was the most abundant organic acid produced by L. fermentum. This is the first report showing that the metabolites produced by the Lactobacillus fermentum TcUESC01 have a potential to be used as an antimicrobial agent against S. mutans, showing anti-adherence and bactericidal activity against planktonic cells of S. mutans. Thus, further studies should be carried out in order to better understand the antimicrobial activity of metabolites of L. fermentum TCUESC01.

20.
Chemphyschem ; 21(6): 476-483, 2020 03 17.
Article in English | MEDLINE | ID: mdl-31943643

ABSTRACT

Herein, a detailed investigation of the surface modification of a zinc oxide (ZnO) nanorod electrode with FeOOH nanoparticles dispersed in glycine was conducted to improve the water oxidation reaction assisted by sunlight. The results were systematically analysed in terms of the general parameters (light absorption, charge separation, and surface for catalysis) that govern the photocurrent density response of metal oxide as photoanode in a photoelectrochemical (PEC) cell. ZnO electrodes surface were modified with different concentration of FeOOH nanoparticles using the spin-coating deposition method, and it was found that 6-layer deposition of glycine-FeOOH nanoparticles is the optimum condition. The glycine plays an important role decreasing the agglomeration of FeOOH nanoparticles over the ZnO electrode surface and increasing the overall performance. Comparing bare ZnO electrodes with the ones modified with glycine-FeOOH nanoparticles an enhanced photocurrent density can be observed from 0.27 to 0.57 mA/cm2 at 1.23 VRHE under sunlight irradiation. The impedance spectroscopy data aid us to conclude that the higher photocurrent density is an effect associated with more efficient surface for chemical reaction instead of electronic improvement. Nevertheless, the charge separation efficiency remains low for this system. The present discovery shows that the combination of glycine-FeOOH nanoparticle is suitable and environmentally-friend cocatalyst to enhance the ZnO nanorod electrode activity for the oxygen evolution reaction assisted by sunlight irradiation.

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