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1.
Proc Natl Acad Sci U S A ; 121(40): e2407821121, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39316046

RESUMO

It is normally supposed that populations of the same species should evolve shared mechanisms of adaptation to common stressors due to evolutionary constraint. Here, we describe a system of within-species local adaptation to coastal habitats, Brassica fruticulosa, and detail surprising strategic variability in adaptive responses to high salinity. These different adaptive responses in neighboring populations are evidenced by transcriptomes, diverse physiological outputs, and distinct genomic selective landscapes. In response to high salinity Northern Catalonian populations restrict root-to-shoot Na+ transport, favoring K+ uptake. Contrastingly, Central Catalonian populations accumulate Na+ in leaves and compensate for the osmotic imbalance with compatible solutes such as proline. Despite contrasting responses, both metapopulations were salinity tolerant relative to all inland accessions. To characterize the genomic basis of these divergent adaptive strategies in an otherwise non-saline-tolerant species, we generate a long-read-based genome and population sequencing of 18 populations (nine inland, nine coastal) across the B. fruticulosa species range. Results of genomic and transcriptomic approaches support the physiological observations of distinct underlying mechanisms of adaptation to high salinity and reveal potential genetic targets of these two very recently evolved salinity adaptations. We therefore provide a model of within-species salinity adaptation and reveal cryptic variation in neighboring plant populations in the mechanisms of adaptation to an important natural stressor highly relevant to agriculture.


Assuntos
Adaptação Fisiológica , Brassica , Salinidade , Brassica/genética , Brassica/fisiologia , Brassica/metabolismo , Adaptação Fisiológica/genética , Tolerância ao Sal/genética , Transcriptoma , Genoma de Planta , Regulação da Expressão Gênica de Plantas , Variação Genética , Sódio/metabolismo , Ecossistema
2.
N Engl J Med ; 389(12): 1108-1120, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37733309

RESUMO

BACKGROUND: Detection of the BRAF V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with BRAF V600 mutations, findings that warrant further evaluation of this combination as first-line therapy. METHODS: In this phase 2 trial, patients with pediatric low-grade glioma with BRAF V600 mutations who were scheduled to receive first-line therapy were randomly assigned in a 2:1 ratio to receive dabrafenib plus trametinib or standard chemotherapy (carboplatin plus vincristine). The primary outcome was the independently assessed overall response (complete or partial response) according to the Response Assessment in Neuro-Oncology criteria. Also assessed were the clinical benefit (complete or partial response or stable disease for ≥24 weeks) and progression-free survival. RESULTS: A total of 110 patients underwent randomization (73 to receive dabrafenib plus trametinib and 37 to receive standard chemotherapy). At a median follow-up of 18.9 months, an overall response occurred in 47% of the patients treated with dabrafenib plus trametinib and in 11% of those treated with chemotherapy (risk ratio, 4.31; 95% confidence interval [CI], 1.7 to 11.2; P<0.001). Clinical benefit was observed in 86% of the patients receiving dabrafenib plus trametinib and in 46% receiving chemotherapy (risk ratio, 1.88; 95% CI, 1.3 to 2.7). The median progression-free survival was significantly longer with dabrafenib plus trametinib than with chemotherapy (20.1 months vs. 7.4 months; hazard ratio, 0.31; 95% CI, 0.17 to 0.55; P<0.001). Grade 3 or higher adverse events occurred in 47% of the patients receiving dabrafenib plus trametinib and in 94% of those receiving chemotherapy. CONCLUSIONS: Among pediatric patients with low-grade glioma with BRAF V600 mutations, dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival, and a better safety profile than standard chemotherapy as first-line therapy. (Funded by Novartis; ClinicalTrials.gov number, NCT02684058.).


Assuntos
Antineoplásicos , Glioma , Proteínas Proto-Oncogênicas B-raf , Criança , Humanos , Glioma/tratamento farmacológico , Glioma/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Antineoplásicos/uso terapêutico
3.
Mol Biol Evol ; 40(7)2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37352150

RESUMO

Snake venoms harbor a wide and diverse array of enzymatic and nonenzymatic toxic components, allowing them to exert myriad effects on their prey. However, they appear to trend toward a few optimal compositional scaffolds, dominated by four major toxin classes: SVMPs, SVSPs, 3FTxs, and PLA2s. Nevertheless, the latter appears to be restricted to vipers and elapids, as it has never been reported as a major venom component in rear-fanged species. Here, by investigating the original transcriptomes from 19 species distributed in eight genera from the Pseudoboini tribe (Dipsadidae: Xenodontinae) and screening among seven additional tribes of Dipsadidae and three additional families of advanced snakes, we discovered that a novel type of venom PLA2, resembling a PLA2-IIE, has been recruited to the venom of some species of the Pseudoboini tribe, where it is a major component. Proteomic and functional analyses of these venoms further indicate that these PLA2s play a relevant role in the venoms from this tribe. Moreover, we reconstructed the phylogeny of PLA2s across different snake groups and show that different types of these toxins have been recruited in at least five independent events in caenophidian snakes. Additionally, we present the first compositional profiling of Pseudoboini venoms. Our results demonstrate how relevant phenotypic traits are convergently recruited by different means and from homologous and nonhomologous genes in phylogenetically and ecologically divergent snake groups, possibly optimizing venom composition to overcome diverse adaptative landscapes.


Assuntos
Colubridae , Proteômica , Animais , Venenos de Serpentes/genética , Fosfolipases A2/genética , Filogenia , Colubridae/genética , Serpentes
4.
Mol Genet Genomics ; 299(1): 73, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39066857

RESUMO

Exploring the intricate relationships between plants and their resident microorganisms is crucial not only for developing new methods to improve disease resistance and crop yields but also for understanding their co-evolutionary dynamics. Our research delves into the role of the phyllosphere-associated microbiome, especially Actinomycetota species, in enhancing pathogen resistance in Theobroma grandiflorum, or cupuassu, an agriculturally valuable Amazonian fruit tree vulnerable to witches' broom disease caused by Moniliophthora perniciosa. While breeding resistant cupuassu genotypes is a possible solution, the capacity of the Actinomycetota phylum to produce beneficial metabolites offers an alternative approach yet to be explored in this context. Utilizing advanced long-read sequencing and metagenomic analysis, we examined Actinomycetota from the phyllosphere of a disease-resistant cupuassu genotype, identifying 11 Metagenome-Assembled Genomes across eight genera. Our comparative genomic analysis uncovered 54 Biosynthetic Gene Clusters related to antitumor, antimicrobial, and plant growth-promoting activities, alongside cutinases and type VII secretion system-associated genes. These results indicate the potential of phyllosphere-associated Actinomycetota in cupuassu for inducing resistance or antagonism against pathogens. By integrating our genomic discoveries with the existing knowledge of cupuassu's defense mechanisms, we developed a model hypothesizing the synergistic or antagonistic interactions between plant and identified Actinomycetota during plant-pathogen interactions. This model offers a framework for understanding the intricate dynamics of microbial influence on plant health. In conclusion, this study underscores the significance of the phyllosphere microbiome, particularly Actinomycetota, in the broader context of harnessing microbial interactions for plant health. These findings offer valuable insights for enhancing agricultural productivity and sustainability.


Assuntos
Doenças das Plantas , Folhas de Planta , Folhas de Planta/microbiologia , Folhas de Planta/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Resistência à Doença/genética , Microbiota/genética , Ecossistema , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Metagenômica/métodos , Metagenoma/genética , Filogenia , Brassicaceae/microbiologia , Brassicaceae/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-38305346

RESUMO

OBJECTIVE: The Berlin algorithm was developed to help diagnosing axial spondyloarthritis (axSpA), but new studies suggest some features typical of SpA are less specific than previously assumed. Furthermore, evidence is lacking for other SpA subtypes (e.g. peripheral SpA). We aimed to review the evidence on the performance of SpA features for diagnosing each SpA subtype. METHODS: Systematic literature review of studies reporting the diagnostic performance of ≥ 1 SpA feature in patients with suspected SpA. The external reference was the rheumatologist's diagnosis of SpA. Meta-analysis was performed, separately for each SpA subtype, to estimate pooled sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios. Meta-regression assessed the effect of covariates (e.g. feature's prevalence) on each feature's performance. RESULTS: Of 13 844 articles screened, 46 were included. Sacroiliitis on magnetic resonance imaging, damage on pelvic radiographs and elevated C-reactive protein (CRP) had the best balance between LR+ and LR- (LR + 3.9-17.0, LR- 0.5-0.7) for diagnosing axSpA. HLA-B27 had an LR+ lower than anticipated (LR + =3.1). Inflammatory back pain (IBP) had low LR + (LR+∼1), but substantially decreased the likelihood of axSpA when absent (LR-=0.3). Conversely, peripheral features and extra-musculoskeletal manifestations showed high LR + (LR+ 1.6-5.0), but were as common in axSpA as no-axSpA (LR-∼1). The specificity of most features was reduced in settings when these were highly prevalent. Limited data precluded a detailed analysis on diagnosing other SpA subtypes. CONCLUSION: Imaging features and CRP have good diagnostic value for axSpA. However, the specificity of other features, especially HLA-B27 and IBP, is lower than previously known.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38937277

RESUMO

OBJECTIVE: To compare health-related quality of life (HRQoL) and work productivity in axial spondyloarthritis (axSpA) and non-axSpA patients with chronic back pain of < 2 years (2 y). METHODS: Baseline and 2 y data of patients included in the SPondyloArthritis Caught Early cohort were analyzed. HRQoL was assessed by the physical (PCS) and mental component summary (MCS) scores of the 36-Item Short-Form Health Survey; and presenteeism, absenteeism, work productivity loss (WPL) and activity impairment (AI) by the Work Productivity and Activity Impairment questionnaire. Linear or zero-inflated negative binomial regression was conducted to compare 2 y outcomes between groups (axSpA and non-axSpA), adjusting for the baseline value, sex, age and use of nonsteroidal anti-inflammatory drugs. RESULTS: There were 265 axSpA and 108 non-axSpA patients: males 52% vs 26%, mean age 29 vs 31 years, respectively. At baseline, non-axSpA patients showed worse PCS (mean 28.6 axSpA vs 26.6 non-axSpA), presenteeism (31.1% vs 37.3%), absenteeism (8.2% vs 10.3%), WPL (34.7% vs 44.1%) and AI (39.6% vs 48.5%). MCS was not impaired in either group. After 2 y, PCS, presenteeism, WPL and AI significantly improved in both groups; absenteeism only in axSpA. In multivariable analysis, axSpA (vs non-axSpA) was associated with 22% less WPL (incidence rate ratio [95% CI]: 0.78 [0.62; 0.98]) and 18% less AI (0.82 [0.69; 0.97]). CONCLUSION: HRQoL and work productivity are more impaired in non-axSpA (vs axSpA) at baseline and still after 2 y. Although most outcomes improve in both groups, axSpA is associated with larger improvements in work productivity and activity impairment.

7.
PLoS Biol ; 19(9): e3001352, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34491982

RESUMO

Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy viral RNAs while sparing the host mRNAs that encode antiviral effectors. Here, we show that highly upregulated interferon-stimulated genes (ISGs), which encode antiviral proteins, have distinctive nucleotide compositions. We propose that self-targeting by antiviral effectors has selected for ISG transcripts that occupy a less self-targeted sequence space. Following interferon (IFN) stimulation, the CpG-targeting antiviral effector zinc-finger antiviral protein (ZAP) reduces the mRNA abundance of multiple host transcripts, providing a mechanistic explanation for the repression of many (but not all) interferon-repressed genes (IRGs). Notably, IRGs tend to be relatively CpG rich. In contrast, highly upregulated ISGs tend to be strongly CpG suppressed. Thus, ZAP is an example of an effector that has not only selected compositional biases in viral genomes but also appears to have notably shaped the composition of host transcripts in the vertebrate interferome.


Assuntos
Fosfatos de Dinucleosídeos , Fatores Reguladores de Interferon/genética , RNA Viral , Proteínas de Ligação a RNA/metabolismo , Células A549 , Linhagem Celular , Humanos , Interferon beta/farmacologia , RNA Mensageiro , Proteínas de Ligação a RNA/genética , Fenômenos Fisiológicos Virais , Vírus
8.
Anal Bioanal Chem ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39164506

RESUMO

Sample preparation in an analytical sequence increases the number of errors, is highly time-consuming, and involves the manipulation of hazardous reagents. Therefore, when an improvement in an analytical method is required, the sample preparation step needs to be optimised or redesigned. Moreover, this step can involve significant toxic reagents and a high volume of waste. In that regard, this study proposes a new procedure based on microwave-assisted wet digestion combining two green strategies: a miniaturised system (with a few microlitres of volume) and the only use of hydrogen peroxide. Three biological samples (human serum, urine, and plant in vitro material) were chosen due to their high potential for disease monitoring, toxicological studies, and biotechnology applications. Several trace elements (Ca, Cd, Co, Cu, Fe, Mg, Mn, Mo, Ni, Se, and Zn) were determined by inductively coupled plasma optical emission spectroscopy and inductively coupled plasma mass spectrometry. For human serum and urine, a certified reference material was used to check for accuracy; the recovery ranged from 72% (Cd, ICP-MS) to 105% (Mg, ICP OES) for serum, while for urine, they varied from 82% (Ni, ICP-MS) to 122% (Zn, ICP-MS). For the soybean callus sample (in vitro plant material), a comparison between the proposed method and the acid digestion method was conducted to evaluate the accuracy, and the results agreed. The detection limits were 0.001-60 µg L-1 (lowest for Cd), thus demonstrating a suitable sensitivity. Moreover, the decomposition efficiency was demonstrated by determining the residual carbon, and a low amount was found in the final product digested (below 0.8% w v-1). A green metric approach was calculated for the proposed method, and according to AGREEprep software, it was found to be around 0.4. Finally, the method was applied to urine samples collected in patients with COVID-19 and soybean callus cultivated with silver nanoparticles. This sample preparation method is a new acidless and miniaturised alternative for elemental analysis involving biological samples.

9.
Oral Dis ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696474

RESUMO

Functional salivary glands (SG) are essential for maintaining oral health, and salivary dysfunction is a persistent major clinical challenge. Several cancer therapies also have off-target effects leading to SG dysfunction. Recent advances highlight the role of SG immune populations in homeostasis, dysfunction and gland regeneration. Here, we review what is known about SG immune populations during development and postnatal homeostasis. We summarize recent findings of immune cell involvement in SG dysfunction following cancer treatments such as irradiation (IR) for head and neck cancers, immune transplant leading to graft-versus-host-disease (GVHD) and immune checkpoint inhibitor (ICI) treatment. The role of immune cells in SG in both homeostasis and disease, is an emerging field of research that may provide important clues to organ dysfunction and lead to novel therapeutic targets.

10.
Proc Natl Acad Sci U S A ; 118(20)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33972420

RESUMO

Venom is a key adaptive innovation in snakes, and how nonvenom genes were co-opted to become part of the toxin arsenal is a significant evolutionary question. While this process has been investigated through the phylogenetic reconstruction of toxin sequences, evidence provided by the genomic context of toxin genes remains less explored. To investigate the process of toxin recruitment, we sequenced the genome of Bothrops jararaca, a clinically relevant pitviper. In addition to producing a road map with canonical structures of genes encoding 12 toxin families, we inferred most of the ancestral genes for their loci. We found evidence that 1) snake venom metalloproteinases (SVMPs) and phospholipases A2 (PLA2) have expanded in genomic proximity to their nonvenomous ancestors; 2) serine proteinases arose by co-opting a local gene that also gave rise to lizard gilatoxins and then expanded; 3) the bradykinin-potentiating peptides originated from a C-type natriuretic peptide gene backbone; and 4) VEGF-F was co-opted from a PGF-like gene and not from VEGF-A. We evaluated two scenarios for the original recruitment of nontoxin genes for snake venom: 1) in locus ancestral gene duplication and 2) in locus ancestral gene direct co-option. The first explains the origins of two important toxins (SVMP and PLA2), while the second explains the emergence of a greater number of venom components. Overall, our results support the idea of a locally assembled venom arsenal in which the most clinically relevant toxin families expanded through posterior gene duplications, regardless of whether they originated by duplication or gene co-option.


Assuntos
Bothrops/genética , Venenos de Crotalídeos/genética , Evolução Molecular , Genoma/genética , Venenos de Serpentes/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Bothrops/classificação , Venenos de Crotalídeos/classificação , Feminino , Perfilação da Expressão Gênica/métodos , Filogenia , Proteoma/metabolismo , Proteômica/métodos , RNA-Seq/métodos , Análise de Sequência de DNA/métodos , Venenos de Serpentes/classificação
11.
Proc Natl Acad Sci U S A ; 118(17)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33875585

RESUMO

The role of natural selection in the evolution of trait complexity can be characterized by testing hypothesized links between complex forms and their functions across species. Predatory venoms are composed of multiple proteins that collectively function to incapacitate prey. Venom complexity fluctuates over evolutionary timescales, with apparent increases and decreases in complexity, and yet the causes of this variation are unclear. We tested alternative hypotheses linking venom complexity and ecological sources of selection from diet in the largest clade of front-fanged venomous snakes in North America: the rattlesnakes, copperheads, cantils, and cottonmouths. We generated independent transcriptomic and proteomic measures of venom complexity and collated several natural history studies to quantify dietary variation. We then constructed genome-scale phylogenies for these snakes for comparative analyses. Strikingly, prey phylogenetic diversity was more strongly correlated to venom complexity than was overall prey species diversity, specifically implicating prey species' divergence, rather than the number of lineages alone, in the evolution of complexity. Prey phylogenetic diversity further predicted transcriptomic complexity of three of the four largest gene families in viper venom, showing that complexity evolution is a concerted response among many independent gene families. We suggest that the phylogenetic diversity of prey measures functionally relevant divergence in the targets of venom, a claim supported by sequence diversity in the coagulation cascade targets of venom. Our results support the general concept that the diversity of species in an ecological community is more important than their overall number in determining evolutionary patterns in predator trait complexity.


Assuntos
Crotalinae/genética , Dieta/tendências , Venenos de Serpentes/genética , Adaptação Biológica/genética , Animais , Crotalinae/metabolismo , Dieta/veterinária , Expressão Gênica/genética , América do Norte , Filogenia , Comportamento Predatório/fisiologia , Proteômica/métodos , Seleção Genética/genética , Venenos de Serpentes/metabolismo , Dente/metabolismo , Transcriptoma/genética
12.
J Ren Nutr ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914380

RESUMO

OBJECTIVE: To assess the association of residual diuresis with sarcopenia in patients with Chronic Kidney Disease (CKD) on hemodialysis. METHODS: Through a cross-sectional study, patients on hemodialysis were subjected to a Dual Energy Radiologic Absorption (DEXA) exam to record muscle mass. Based on the volume of urine collected in 24 hours, patients were classified as anuric (diuresis ≤ 100 mL/day) or non-anuric (diuresis > 100 mL/day). Functional performance was evaluated by Short Physical Performance Battery (SPPB) and muscle strength by handgrip strength and 5-repetition sit-to-stand test. The association between the absence of residual urine and the presence of sarcopenia, low SPPB, and low muscle strength was analyzed using a binary logistic regression model. RESULTS: Ninety-two patients, with a mean age of 54.4 years (95% CI 51.3 - 57.4) and with a mean diuresis volume of 476.3 mL/day (95% CI 320.4 - 632.2) were evaluated (48 anuric and 44 non-anuric). Anuric patients had a 2.77 (95% CI 1.14 - 6.73) times greater probability of sarcopenia and had a 3.55 (1.14 - 11.0) times greater probability of low SPPB, regardless of gender, age, and time on dialysis. Gender was the other associated variable for the presence of sarcopenia, with males having a 3.30 (95% CI 1.34 - 8.13) times higher risk. There were no associations with muscle strength. CONCLUSION: The absence of residual diuresis in patients on hemodialysis is associated with a higher risk of sarcopenia and low functional performance.

13.
Chem Biodivers ; 21(7): e202400444, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38670923

RESUMO

Fungal infections are a public health problem that mainly affects immunosuppressed people, Candida spp. have been responsible for most sources of contamination and invasive fungal infections described around the world. The need arises to find new therapeutic approaches to combat growing infections. Plants and natural products have been considered a valuable source for discovering new molecules with active ingredients. Diosgenin is a sapogenin found in the families of Leguminosae and Dioscoreaceae, it is obtained mainly from the dioscin saponin through the hydrolysis method, it is a phytochemical that has been highlighted in the treatment of various diseases, as well as in combating microbial resistance. The present study aimed to evaluate the susceptibility of fungal strains to diosgenin, as well as verify the association with the reference drug and evaluate the inhibition of the virulence factor through morphological changes in the yeast state to the filamentous form of hyphae and pseudohyphae in strains of Candida albicans, Candida tropicalis and Candida krusei using the broth microdilution method and microculture technique. Antifungal assays revealed that diosgenin was not able to inhibit the growth of the tested strains. However, it was able to inhibit the fungal dimorphism of the strains evaluated, however further studies are recommended to verify its effectiveness against other virulence factors.


Assuntos
Antifúngicos , Candida , Diosgenina , Testes de Sensibilidade Microbiana , Diosgenina/farmacologia , Diosgenina/química , Diosgenina/análogos & derivados , Antifúngicos/farmacologia , Antifúngicos/química , Candida/efeitos dos fármacos , Virulência/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade
14.
Chem Biodivers ; 21(8): e202400786, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38777789

RESUMO

This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50>40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5 % was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors.


Assuntos
Analgésicos , Simulação de Acoplamento Molecular , Peixe-Zebra , Animais , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Tropanos/farmacologia , Tropanos/isolamento & purificação , Tropanos/química , Edema/tratamento farmacológico , Edema/induzido quimicamente , Carragenina/farmacologia , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 1/metabolismo , Bignoniaceae/química , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/química , Canais Iônicos Sensíveis a Ácido/metabolismo , Canais Iônicos Sensíveis a Ácido/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Estrutura Molecular
15.
Clin Oral Investig ; 28(9): 489, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39153029

RESUMO

OBJECTIVE: The present study aimed to determine the salivary flow and metabolomic profile of stimulated and unstimulated saliva in children. MATERIALS AND METHODS: Children who attended the Pediatric Dentistry Clinic of the State University of Rio de Janeiro -UERJ between 3 and 12 years of age were selected. Unstimulated and stimulated whole saliva, using mechanical stimulus, were collected. The samples were centrifuged at 12,000 g, 4oC for 1 h. The 1H- NMR spectra were acquired in 500 MHz equipment. The data were extracted into 0.03 ppm buckets in AMIX, and multivariate analysis (PLS-DA and O-PLS-DA) was performed in Metaboanalyst 2.0. For other analyses, such as salivary flow, the data was tabulated in the SPSS 20.0 statistical package, analyzed descriptively, and after applying the Wilcoxon test. The interval of confidence was set at 95%. RESULTS: The mean age was 7.5 (± 1.94), and 47.0% (n = 31) were female, 63.6% (n = 42). The median flow rate for stimulated saliva was 0.74 (IC 0.10-2.40) and was statistically higher (p < 0.001; Wilcoxon test) than unstimulated was 0.39 (IC 0.00-1.80). Children older than seven years old also presented a higher difference between unstimulated and stimulated saliva (p = 0.003; Mann-Whitney test). The PLS-DA and O-PLS-DA demonstrated a different profile in stimulated and unstimulated saliva. Acetate, glucose, propionate, and lysine were higher in the unstimulated whole saliva than in stimulated saliva. Isoleucine, N-acetyl sugar, hydroxybutyrate, glutamate, leucine, propionate, butyrate, valine, isoleucine, succinate, saturated fatty acid, and histidine were found in greater amounts in the saliva of patients with stimulated saliva. CONCLUSION: The stimulated saliva presented a higher flow rate, and older children exhibited a higher flow rate resulting from it's the stimulus. The mechanical stimulus increased the levels of the major metabolites.


Assuntos
Metabolômica , Saliva , Humanos , Saliva/química , Saliva/metabolismo , Feminino , Criança , Masculino , Pré-Escolar , Taxa Secretória , Espectroscopia de Ressonância Magnética/métodos , Brasil
16.
Molecules ; 29(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38930901

RESUMO

This study presents fibers based on methacrylic acid-methyl methacrylate (Eudragit L100) as Cu(II) adsorbents, resulting in antimicrobial complexes. Eudragit L100, an anionic copolymer synthesized by radical polymerization, was electrospun in dimethylformamide (DMF) and ethanol (EtOH). The electrospinning process was optimized through a 22-factorial design, with independent variables (copolymer concentration and EtOH/DMF volume ratio) and three repetitions at the central point. The smallest average fiber diameter (259 ± 53 nm) was obtained at 14% w/v Eudragit L100 and 80/20 EtOH/DMF volume ratio. The fibers were characterized using scanning electron microscopy (SEM), infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR), and differential scanning calorimetry (DSC). The pseudo-second-order mechanism explained the kinetic adsorption toward Cu(II). The fibers exhibited a maximum adsorption capacity (qe) of 43.70 mg/g. The DSC analysis confirmed the Cu(II) absorption, indicating complexation between metallic ions and copolymer networks. The complexed fibers showed a lower degree of swelling than the non-complexed fibers. The complexed fibers exhibited bacteriostatic activity against Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. This study successfully optimized the electrospinning process to produce thin fibers based on Eudragit L100 for potential applications as adsorbents for Cu(II) ions in aqueous media and for controlling bacterial growth.


Assuntos
Cobre , Ácidos Polimetacrílicos , Cobre/química , Ácidos Polimetacrílicos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Metacrilatos/química , Cinética , Varredura Diferencial de Calorimetria , Testes de Sensibilidade Microbiana
17.
J Sci Food Agric ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39113580

RESUMO

BACKGROUND: Multidrug-resistant bacteria in humans have prompted the search for alternative solutions derived from herbal medicines that can substitute antibiotics in livestock production. Thus, the goal of this study was to evaluate the phytogenic properties of Marrubium vulgare infusion (MVI) on weaned pigs. Thirty animals were randomly divided into five groups of six animals, each receiving a physiological solution, clenbuterol and the infusion extract at doses of 0.01 (MVI 1%), 0.1 (MVI 10%) and 0.2 (MVI 20%) mg kg-1 for 28 days. Biochemical parameters and the liquid chromatographic-electrospray ionization-mass spectrometric (LC-ESI-MS) chemical profiles of the infusion extract and animal serum were studied. RESULTS: The doses MVI 1 and 10% led to weight gain higher than the controls. No significant changes were noted in the biochemical parameters including erythrocytes, hemoglobin, hematocrit, mean corpuscular volume and others. Evaluation of enzymatic levels in blood revealed no significant changes. LC-ESI-MS data of MVI showed the presence of 34 secondary metabolites, and successive chromatographic purification of MVI yielded marrubiin and apigenin as major components. LC-ESI-MS data of animal serum showed the presence of a diterpene, a flavonoid and diverse cholic acid derivatives. CONCLUSION: Results indicated the doses MVI 1 and 10% promote weight gain with no significant alterations in blood biochemicals, and liver and kidney function. © 2024 Society of Chemical Industry.

18.
Microb Pathog ; 174: 105925, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36462578

RESUMO

Antimicrobial drugs are of great importance in the control of bacterial infections. Its indiscriminate use contributes to the consolidation of bacterial resistance. Its applicability is due to its secondary metabolites, such as saponins, which are compounds with relevant antibacterial action. Hecogenin acetate is a saponin present in plants of the agave genus with analgesic, antioxidant, antinociceptive, cardioactive, anticancer, antifungal and antimicrobial activity. The present work aimed to identify the antibacterial activity of hecogenin acetate against strains of E. coli, P. aeruginosa and S. aureus and to investigate the NorA and MepA efflux pump inhibitory activity of S. aureus strains. The Minimum Inhibitory Concentration was evaluated by broth microdilution. The Antibiotic Activity Modifier effect and the assessment of efflux pump inhibition were evaluated by microdilution with sub-inhibitory concentrations. Hecogenin acetate showed minimal inhibitory concentration without significant relevance. In the evaluation of the potentiating activity of the antibiotic action, a greater antagonistic behavior is noticed. In the analyzes performed with the efflux pump, it was noticed that the hecogenin acetate does not interfere in the efflux pump mechanism of the analyzed bacteria.


Assuntos
Antibacterianos , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Staphylococcus aureus , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Testes de Sensibilidade Microbiana , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo
19.
Am J Bot ; 110(10): e16235, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37661935

RESUMO

PREMISE: Cacti are characteristic elements of the Neotropical flora and of major interest for biogeographic, evolutionary, and ecological studies. We tested global biogeographic boundaries for Neotropical Cactaceae using specimen-based occurrences, coupled with data from visual observations, as a means to tackle the known collection biases in the family. METHODS: Species richness and record density were assessed for preserved specimens and human observations, and a bioregional scheme tailored to Cactaceae was produced using the interactive web application Infomap Bioregions, based on data from 261,272 point records cleaned through automated and manual steps. RESULTS: We found that areas in Mexico and southwestern USA, in eastern Brazil, and along the Andean region have the greatest density of records and the highest species richness. Human observations complement information from preserved specimens substantially, especially along the Andes. We propose 24 cactus bioregions, among which the most species-rich are northern Mexico/southwestern USA, central Mexico, southern central Mexico, Central America, Mexican Pacific coast, central and southern Andes, northwestern Mexico/extreme southwestern USA, southwestern Bolivia, northeastern Brazil, and Mexico/Baja California. CONCLUSIONS: The bioregionalization proposed shows biogeographic boundaries specific to cacti and can thereby aid further evolutionary, biogeographic, and ecological studies by providing a validated framework for further analyses. This classification builds upon, and is distinctive from, other expert-derived regionalization schemes for other taxa. Our results showcase how observation data, including citizen-science records, can complement traditional specimen-based data for biogeographic research, particularly for taxa with specific specimen collection and preservation challenges and those that are threatened or internationally protected.


Assuntos
Cactaceae , Humanos , México , Evolução Biológica , Brasil , Bolívia
20.
Avian Pathol ; 52(5): 362-376, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37470411

RESUMO

Avibacterium paragallinarum (A. paragallinarum) is the aetiological agent of infectious coryza (IC) in chickens and characterized by acute respiratory distress and severe drop in egg production. Vaccination is important in the control of IC outbreaks and the efficacy of vaccination is dependent on A. paragallinarum serovars included in the vaccine. Classical serotyping of A. paragallinarum is laborious and hampered by poor availability of antigens and antisera. The haemagglutinin, important in classical serotyping, is encoded by the HMTp210 gene. HMTp210 gene analysis has been shown to have potential as alternative to classical serotyping. The aim of the present study was to further investigate the potential of sequence analyses of partial region 1 of the HMTp210 gene, the HMTp210 hypervariable region and the concatenated sequences of both fragments. For this analysis, 123 HMTp210 gene sequences (field isolates, A. paragallinarum serovar reference strains and vaccine strains) were included. Evaluation of serovar references and vaccine strains revealed a need for critical evaluation, especially within Page serovar B and C. Phylogenetic analysis of HMTp210 region 1 resulted in a separation of Page serovar A, B and C strains. Analysis of the HMTp210 HVR alone was not sufficient to discriminate all nine different Kume serovar references. The concatenated sequences of HMTp210 region 1 and HMTp210 HVR resulted in 14 clusters with a high correlation with Page serovar and with the nine currently known Kume serovars and is therefore proposed as a novel genotyping method that could be used as an alternative for classical serotyping of A. paragallinarum.


Assuntos
Infecções por Haemophilus , Haemophilus paragallinarum , Doenças das Aves Domésticas , Animais , Sorotipagem/veterinária , Infecções por Haemophilus/veterinária , Infecções por Haemophilus/microbiologia , Genótipo , Filogenia , Galinhas , Haemophilus paragallinarum/genética , Doenças das Aves Domésticas/microbiologia
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