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Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens.Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p-substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses.Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa, with minimum inhibitory concentrations ranging from 16 to 128 µg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128 µg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features.Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.
[Box: see text].
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Forestry constitutes an important agronomical activity in Uruguay, involving the cultivation of exotic trees mainly for cellulose pulp production with Eucalyptus species. Over the last decade, E. smithii emerged as a species of interest for cellulose pulping. However, its rapid expansion has coincided with high mortality rates among young trees ranging from 5 to 85%, especially during the first and second summer after plantation. Disease surveys conducted on nine E. smithii commercial fields and three nurseries in southern and eastern Uruguay, yielded a collection of 25 isolates from E. smithii root rot belonging to the Nectriaceae family. In this study, we aimed to identify and characterize these isolates employing phenotypical and molecular studies and to assess their pathogenicity on E. smithii seedlings. Based on morphological features, the Nectriaceae isolates were subdivided into two groups, one resembling Calonectria (n=15) and another Cylindrocarpon-like (n=10). DNA sequences of the partial histone H3 (his3), actine, calmodulin, RNA polymerase II second largest subunit, translation elongation factor 1-alpha (tef1) and ß-tubulin (tub2) genes were amplified for Calonectria, as well as partial his3, tef1, tub2 and internal-transcribed spacer and intervening 5.8S (ITS) for the Cylindrocarpon-like group. Based on phylogenetic analysis and phenotypical features three species were identified and characterized; Calonectria pauciramosa (n=15), Dactylonectria novozelandica (n=2), and a novel taxon which we describe here as Ilyonectria charruensis sp. nov. (n=8). The pathogenicity trials revealed that isolates from the three species significantly reduced both shoot and root dry weights of inoculated E. smithii seedlings compared to control plants.
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INTRODUCTION: Nattokinase (NK) is the primary ingredient of natto, a traditional Asian food made from fermented soybean by Bacillus subtilis natto. Studies have shown that natto reduces the risk of cardiovascular disease (CVD) mortality due to its fibrinolytic and antithrombotic properties. A new field of studies also demonstrates that NK can mitigate molecular pathways related to inflammation and oxidative stress and can be considered an adjuvant strategy for use in many non-communicable diseases (NCDs). This paper is a narrative review of the literature. A search was conducted in PubMed and ScienceDirect up to July 2024. AREAS COVERED: This review discusses the possible effects of NK on mitigating the common complications of NCDs, such as inflammation and oxidative stress. In addition, it provides an update on the most addressed areas related to NK's fibrinolytic and antithrombotic activities. EXPERT OPINION: Due to the fibrinolytic and antithrombotic activity of nattokinase, and more recently added to the anti-inflammatory and antioxidant effects, this enzyme can be used as a new adjuvant therapeutic strategy to mitigate inflammation and oxidative stress in NCDs, including CVD.
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Previous studies conducted in the municipality of Sibaté (Colombia) have revealed alarming findings regarding asbestos exposure in the region, as it is the site of the country's first mesothelioma cluster. Non-occupational asbestos exposure events were identified in this population, and the young age of the mesothelioma cases at the time of diagnosis suggests that asbestos exposure occurred during their childhood. The creation of landfilled zones in the 1980s and 1990s, utilizing friable asbestos among other disposed materials, may have been a significant asbestos exposure event contributing to the elevated number of mesothelioma cases. The objective of this study was to model various historical exposure scenarios related to the creation and interaction of the population with asbestos-contaminated landfilled zones, in light of the absence of asbestos monitoring in the region. The models utilized a multi-agent simulation process, focusing on a 10-year period (1986-1995). Various relevant variables were incorporated into the modeling process, including, for example, the number of children playing in the landfilled zones and the percentage of children carrying asbestos fibers on their clothes to their homes. A range of values for input data for the models were utilized, spanning from very conservative numbers to exposure-promoting values. The average number of exposed individuals estimated over 750 simulation runs, considering all scenarios, was 571, with a range between 31 and 3800 exposed individuals. The use of multi-agent simulation models can assist the understanding of past asbestos exposure events, especially when there is a lack of environmental surveillance data.
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Amianto , Exposición a Riesgos Ambientales , Amianto/análisis , Humanos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Mesotelioma/epidemiología , Mesotelioma/inducido químicamenteRESUMEN
Rhizophora mangle is commonly used in traditional medicine to treat infections, reduce inflammation, and promote healing. This study aimed to analyze the phytochemical profile of the methanolic extract of R. mangle leaves (MELRm) and evaluate its in vitro schistosomicidal activity against Schistosoma mansoni as well as its cytotoxicity. Plant material was collected in Itamaracá City, Pernambuco, Brazil. The extract was analyzed using UV/Vis spectrophotometry and high-performance liquid chromatography (HPLC). The motility, mortality, and cell viability of adult worms were assessed in a schistosomicidal assay, while cytotoxicity was evaluated through a colorimetric assay with MTT on RAW 264.7 cells. The primary compounds identified in MELRm were phenolic compounds. In the schistosomicidal assay, all concentrations of MELRs induced changes in the motility of adult worms. At a concentration of 400 µg/mL, MELRs resulted in 56.25% mortality after 72 h of incubation. After 120 h, mortality rates of 75%, 62.5%, and 50% were observed at MELRm concentrations of 400, 200, and 100 µg/mL, respectively. No eggs were detected at any MELRm concentration. MELRs did not show cytotoxicity towards RAW 264.7 cells at the concentrations tested. These results indicate that MELRs demonstrate schistosomicidal activity in vitro, suggesting they are promising candidates for in vivo studies.
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This study presents extended Immunity Agent-Based Model (IABM) simulations to evaluate vaccination strategies in controlling the spread of infectious diseases. The application of IABM in the analysis of vaccination configurations is innovative, as a vaccinated individual can be infected depending on how their immune system acts against the invading pathogen, without a pre-established infection rate. Analysis at the microscopic level demonstrates the impact of vaccination on individual immune responses and infection outcomes, providing a more realistic representation of how the humoral response caused by vaccination affects the individual's immune defense. At the macroscopic level, the effects of different population-wide vaccination strategies are explored, including random vaccination, targeted vaccination of specific demographic groups, and spatially focused vaccination. The results indicate that increased vaccination rates are correlated with decreased infection and mortality rates, highlighting the importance of achieving herd immunity. Furthermore, strategies focused on vulnerable populations or densely populated regions prove to be more effective in reducing disease transmission compared to randomly distributed vaccination. The results presented in this work show that vaccination strategies focused on highly crowded regions are more efficient in controlling epidemics and outbreaks. Results suggest that applying vaccination only in the densest region resulted in the suppression of infection in that region, with less intense viral spread in areas with lower population densities. Strategies focused on specific regions, in addition to being more efficient in reducing the number of infected and dead people, reduce costs related to transportation, storage, and distribution of doses compared to the random vaccination strategy. Considering that, despite scientific efforts to consolidate the use of mass vaccination, the accessibility, affordability, and acceptability of vaccines are problems that persist, investing in the study of strategies that mitigate such issues is crucial in the development and application of government policies that make immunization systems more efficient and robust.
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Bioinformatics has emerged as a valuable tool for screening drugs and understanding their effects. This systematic review aimed to evaluate whether in silico studies using anti-obesity peptides targeting therapeutic pathways for obesity, when subsequently evaluated in vitro and in vivo, demonstrated effects consistent with those predicted in the computational analysis. The review was framed by the question: "What peptides or proteins have been used to treat obesity in in silico studies?" and structured according to the acronym PECo. The systematic review protocol was developed and registered in PROSPERO (CRD42022355540) in accordance with the PRISMA-P, and all stages of the review adhered to these guidelines. Studies were sourced from the following databases: PubMed, ScienceDirect, Scopus, Web of Science, Virtual Heath Library, and EMBASE. The search strategies resulted in 1015 articles, of which, based on the exclusion and inclusion criteria, 7 were included in this systematic review. The anti-obesity peptides identified originated from various sources including bovine alpha-lactalbumin from cocoa seed (Theobroma cacao L.), chia seed (Salvia hispanica L.), rice bran (Oryza sativa), sesame (Sesamum indicum L.), sea buckthorn seed flour (Hippophae rhamnoides), and adzuki beans (Vigna angularis). All articles underwent in vitro and in vivo reassessment and used molecular docking methodology in their in silico studies. Among the studies included in the review, 46.15% were classified as having an "uncertain risk of bias" in six of the thirteen criteria evaluated. The primary target investigated was pancreatic lipase (n = 5), with all peptides targeting this enzyme demonstrating inhibition, a finding supported both in vitro and in vivo. Additionally, other peptides were identified as PPARγ and PPARα agonists (n = 2). Notably, all peptides exhibited different mechanisms of action in lipid metabolism and adipogenesis. The findings of this systematic review underscore the effectiveness of computational simulation as a screening tool, providing crucial insights and guiding in vitro and in vivo investigations for the discovery of novel anti-obesity peptides.
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Simulación por Computador , Obesidad , Péptidos , Animales , Humanos , Fármacos Antiobesidad/química , Fármacos Antiobesidad/farmacología , Biología Computacional , Simulación del Acoplamiento Molecular , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Péptidos/química , Péptidos/farmacologíaRESUMEN
English walnut (Juglans regia) cultivation has been expanding in recent years in Chile, with a surface of 9,000 ha planted in the Maule Region (35° 26' S, 71° 40' W), central Chile. In a field survey conducted between August (2022) and January (2023) in three localities of the Maule Region, several declined trees were observed. English walnuts exhibited small chlorotic leaves, cankers, dead twigs, and dieback of branches, with an incidence of 10 to 35% of trees affected per orchard. Internally, diseased branches exhibit brown to dark brown wood cankers. Symptomatic branches (n = 30) were collected and surface disinfected with 96% ethanol, and flamed. Pieces of wood (approximately 5 mm) were placed on potato dextrose agar (PDA), supplemented with 0.005% tetracycline, 0.01% streptomycin, and 0.1% Igepal CO-630 (Díaz et al. 2018), and incubated at 22°C for 5 days in darkness. Four isolates (VLC-1-6-20, VLC-1-10-20, VLC-1-12-20, and VLC-1-15-20) exhibited moderate growth rates (16.4 mm/day), developing a white hue to olivaceous black colonies after 7 days at 22°C on PDA. Chlamydospores were absent. Black pycnidia were formed individually or in clusters. The isolates produced aseptate, hyaline, and fusiform, with base truncate conidia measuring 24.8 ± 1.6 x 6.8 ± 0.63 µm (l/w = 3.1; n = 50). The four isolates characterized were amplified using of the internal transcribed spacer (ITS1/ITS4), a portion of beta-tubulin (Bt2a/Bt2b), and part of the translation elongation factor 1- α (EF1-728/EF1-968) genes (Phillips et al. 2013). Blast analyses showed 100, 99 and 100 % identity with ex-type isolate PD-484 of Neofusicoccum nonquaesitum for ITS (deposited as GenBank accession no. PP697845 to PP697848), Bt (PP789576 to PP789579) and EF1 (PP830824 to PP830827) regions, respectively. Combined phylogenetic analysis using MEGA 7 software and the maximum likelihood test clustered the four isolates with ex-type of N. nonquaesitum. Pathogenicity was performed using two isolates (VLC-1-6-20 and VLC-1-10-20), which were inoculated in healthy tree walnuts cv. Chandler (8 years old), using 40 µl of mycelial suspension (105 fragments of mycelium/ml) on rounded wounds in the middle of each attached young branch (n=30 branches) (Twizeyimana et al. 2013). Sterile distilled water was used as a control treatment. Pathogenicity tests were repeated twice. After 6 months, necrotic streaks with mean lengths of 13 mm and 28 mm were observed in the middle of wounded young branches. No necrotic lesions were observed in the control treatments. Reisolation of N. nonquaesitum was positive (100%) only from inoculated branches and molecularly identified (EF1-a), fulfilling Koch's postulates. Previously, N. nonquaesitum has been reported causing dieback on English walnut in California (Chen et al. 2014). To our knowledge, this is the first report of N. nonquaesitum causing canker and branch dieback of English walnut in central Chile. Previously, Diplodia mutila, Dothiorella sarmentorum, and N. austral have been associated with walnut dieback in Chile (Díaz et al. 2018; Iqbal et al. 2023; Barcos et al. 2023). In conclusion, it is imperative to implement epidemiological studies to avoid the spread and severity of branch dieback of walnuts in the Maule region, central Chile.
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This work aims to develop and validate a framework for the multiscale simulation of the biological response to ionizing radiation in a population of cells forming a tissue. We present TOPAS-Tissue, a framework to allow coupling two Monte Carlo (MC) codes: TOPAS with the TOPAS-nBio extension, capable of handling the track-structure simulation and subsequent chemistry, and CompuCell3D, an agent-based model simulator for biological and environmental behavior of a population of cells. We verified the implementation by simulating the experimental conditions for a clonogenic survival assay of a 2-D PC-3 cell culture model (10 cells in 10,000 µm2) irradiated by MV X-rays at several absorbed dose values from 0-8 Gy. The simulation considered cell growth and division, irradiation, DSB induction, DNA repair, and cellular response. The survival was obtained by counting the number of colonies, defined as a surviving primary (or seeded) cell with progeny, at 2.7 simulated days after irradiation. DNA repair was simulated with an MC implementation of the two-lesion kinetic model and the cell response with a p53 protein-pulse model. The simulated survival curve followed the theoretical linear-quadratic response with dose. The fitted coefficients α = 0.280 ± 0.025/Gy and ß = 0.042 ± 0.006/Gy2 agreed with published experimental data within two standard deviations. TOPAS-Tissue extends previous works by simulating in an end-to-end way the effects of radiation in a cell population, from irradiation and DNA damage leading to the cell fate. In conclusion, TOPAS-Tissue offers an extensible all-in-one simulation framework that successfully couples Compucell3D and TOPAS for multiscale simulation of the biological response to radiation.
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Reparación del ADN , Método de Montecarlo , Radiación Ionizante , Humanos , Reparación del ADN/efectos de la radiación , Simulación por Computador , Modelos Biológicos , Supervivencia Celular/efectos de la radiación , Daño del ADN , Relación Dosis-Respuesta en la Radiación , Línea Celular Tumoral , Roturas del ADN de Doble Cadena/efectos de la radiaciónRESUMEN
The advancement of fungal biocontrol agents depends on replacing cereal grains with low-cost agro-industrial byproducts for their economical mass production and development of stable formulations. We propose an innovative approach to develop a rice flour-based formulation of the beneficial biocontrol agent Trichoderma asperelloides CMAA1584 designed to simulate a micro-bioreactor within the concept of full biorefinery process, affording in situ conidiation, extended shelf-life, and effective control of Sclerotinia sclerotiorum, a devastating pathogen of several dicot agricultural crops worldwide. Rice flour is an inexpensive and underexplored byproduct derived from broken rice after milling, capable of sustaining high yields of conidial production through our optimized fermentation-formulation route. Conidial yield was mainly influenced by nitrogen content (0.1% w/w) added to the rice meal coupled with the fermentor type. Hydrolyzed yeast was the best nitrogen source yielding 2.6 × 109 colony-forming units (CFU)/g within 14 days. Subsequently, GControl, GLecithin, GBreak-Thru, GBentonite, and GOrganic compost+Break-Thru formulations were obtained by extrusion followed by air-drying and further assessed for their potential to induce secondary sporulation in situ, storage stability, and efficacy against Sclerotinia. GControl, GBreak-Thru, GBentonite, and GOrganic compost+Break-Thru stood out with the highest number of CFU after sporulation upon re-hydration on water-agar medium. Shelf-life of formulations GControl and GBentonite remained consistent for > 3 months at ambient temperature, while in GBentonite and GOrganic compost+Break-Thru formulations remained viable for 24 months during refrigerated storage. Formulations exhibited similar efficacy in suppressing the myceliogenic germination of Sclerotinia irrespective of their concentration tested (5 × 104 to 5 × 106 CFU/g of soil), resulting in 79.2 to 93.7% relative inhibition. Noteworthily, all 24-month-old formulations kept under cold storage successfully suppressed sclerotia. This work provides an environmentally friendly bioprocess method using rice flour as the main feedstock to develop waste-free granular formulations of Trichoderma conidia that are effective in suppressing Sclerotinia while also improving biopesticide shelf-life. KEY POINTS: ⢠Innovative "bioreactor-in-a-granule" system for T. asperelloides is devised. ⢠Dry granules of aerial conidia remain highly viable for 24 months at 4 °C. ⢠Effective control of white-mold sclerotia via soil application of Trichoderma-based granules.
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Ascomicetos , Reactores Biológicos , Fermentación , Oryza , Esporas Fúngicas , Reactores Biológicos/microbiología , Ascomicetos/crecimiento & desarrollo , Ascomicetos/metabolismo , Oryza/microbiología , Esporas Fúngicas/crecimiento & desarrollo , Nitrógeno/metabolismo , Hypocreales/metabolismo , Hypocreales/crecimiento & desarrollo , Agentes de Control Biológico/química , Trichoderma/metabolismo , Trichoderma/crecimiento & desarrollo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & controlRESUMEN
Giardiasis is an infection of the small intestine by protozoa of the genus Giardia, which has a wide range of susceptible hosts, including domestic and wild animals and humans. Giardia is a zoonotic agent and represents one of the main human parasites, with high prevalence and great importance in public health. This report aims to describe the parasitism of a non-captive Chital deer (Axis axis) by Giardia duodenalis. The animal, after being rescued by soldiers from the 2nd Platoon of the 2nd Company of the 2nd Battalion of the Environmental Military Police of the State of Santa Catarina, was sent to the Wildlife Studies Center (NEVS) of the University of Western Santa Catarina (UNOESC). During clinical care, an exposed fracture in the left pelvic limb and signs of acute respiratory failure were found. Fecal samples were collected for later parasitological diagnosis. Two techniques were applied: centrifugal flotation with zinc sulfate, to diagnose parasites of the gastrointestinal system, and Baermann, to search for parasitism in the respiratory tract. The investigation revealed the presence of Giardia duodenalis. The animal died on the same day of its arrival due to a cardiorespiratory arrest. The presence of this parasite in an invasive exotic deer species highlights its epidemiological importance, as it can act as a source of infection and spread the disease to humans and other animals.
Giardíase é uma infecção do intestino delgado por protozoários do gênero Giardia, o qual apresenta uma ampla variedade de hospedeiros suscetíveis, incluindo animais domésticos, selvagens e também humanos. Giardia é um agente zoonótico, e representa um dos principais parasitas de humanos, com alta prevalência e grande importância em saúde pública. Este relato tem como objetivo descrever o parasitismo de um indivíduo de cervo Chital (Axis axis) de vida livre por Giardia duodenalis. O animal, após ser resgatado por soldados do 2º Pelotão da 2ª Companhia do 2º Batalhão da Polícia Militar Ambiental do Estado de Santa Catarina, foi encaminhado ao Núcleo de Estudos em Vida Selvagem (NEVS) da Universidade do Oeste de Santa Catarina (UNOESC). Durante o atendimento clínico foi constatada fratura exposta no membro pélvico esquerdo e sinais de insuficiência respiratória aguda. Amostras de fezes foram coletadas para posterior diagnóstico parasitológico. Para isso, foram usadas duas técnicas: centrífugo-flutuação em sulfato de zinco, com o objetivo de diagnosticar parasitas do sistema gastrointestinal, e Baermann, com o objetivo de pesquisar parasitas do trato respiratório. Os achados revelaram presença de cistos de Giardia duodenalis. O animal morreu no mesmo dia de sua chegada, devido a uma parada cardiorrespiratória. A presença desse parasito em uma espécie de cervídeo exótico invasor destaca sua importância epidemiológica, pois o mesmo pode atuar como fonte de infecção e de disseminação da doença para o ser humano e/ou outros animais.
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Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. Due to its zoonotic transmission in Brazil, S. brasiliensis represents a significant health threat to humans and domestic animals. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains of S. brasiliensis and S. schenckii have shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activity in vitro against different strains of S. brasiliensis and S. schenckii. Fluorescent miltefosine localizes to the Sporothrix cell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreases S. brasiliensis fungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-α, IL-6, and IL-10 production. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis. IMPORTANCE: Sporotrichosis is an endemic disease in Latin America caused by different species of Sporothrix. This fungus can infect domestic animals, mainly cats and eventually dogs, as well as humans. Few drugs are available to treat this disease, such as itraconazole, terbinafine, and amphotericin B, but resistance to these agents has risen in the last few years. Alternative new therapeutic options to treat sporotrichosis are essential. Here, we propose milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, as a possible therapeutic alternative for treating sporotrichosis. Milteforan decreases S. brasiliensis fungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production.
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Antifúngicos , Enfermedades de los Gatos , Sporothrix , Esporotricosis , Animales , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiología , Esporotricosis/veterinaria , Gatos , Sporothrix/efectos de los fármacos , Antifúngicos/farmacología , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/microbiología , Humanos , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Fosforilcolina/uso terapéutico , Brasil , Pruebas de Sensibilidad Microbiana , Perros , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , RatonesRESUMEN
Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3âº-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3âº-MIH and its potential to enhance breast cancer management.
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Neoplasias de la Mama , Imagen por Resonancia Magnética , Nanopartículas , Dióxido de Silicio , Nanomedicina Teranóstica , Dióxido de Silicio/química , Animales , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Nanomedicina Teranóstica/métodos , Imagen por Resonancia Magnética/métodos , Ratones , Línea Celular Tumoral , Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Medios de Contraste/química , Gadolinio/química , Porosidad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Achieving more sustainable adaptation to social-environmental change demands the transformation of the narratives that provide the rationale for risk governance. These narratives often reflect long-standing beliefs about social and political relationships, ascribe actions and responsibilities, and specify solutions to risk. When such solutions are implemented through material investments in landscapes, these narratives become embedded in physical infrastructure with long legacies. Dominant narratives can mask a range of divergent problem framings. By masking alternatives, narratives can contribute to the persistence of unsustainable governance trajectories. Decision-support tools have begun to represent narratives as drivers of system dynamics; making narratives visible can reveal opportunities for more sustainable governance. We present the results of the project "The Dynamics of Multi-Scalar Adaptation in the Megalopolis", a dynamic, exploratory model of socio-hydrological risks in Mexico City that was designed to both endogenize and simultaneously challenge the dominant narratives that characterize water-risk governance in the city. Qualitative data characterize dominant narratives at city and borough scales. An agent-based model, informed by multicriteria decision analysis and coupled with hydrological, urbanization, and climatic model inputs, permitted the development of exploratory governance scenarios designed to challenge dominant narratives. Scenarios revealed how dominant narratives may contribute to the persistence of vulnerability "hotspots" in the city, despite stated goals of equity and vulnerability alleviation. Participatory workshops with representatives of the city government illustrate how making such narratives visible through exploratory modeling can lead to a questioning of prior assumptions and causal relations, recognition of a need for intersectoral collaboration, and insights into potential management strategies.
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European chestnut (Castanea sativa Mill.) currently reaches 1,470 ha, distributed from the Maule region to the Los Rios region in Chile. Almost 3000 tons of fruit have been exported in the last three years. A survey was carried out in January 2023 in an eight-year-old orchard located in Vilcún (38°34'46.22"S 72° 9'58.61"O), Araucanía Region. Chestnut trees with branch die back and reduced growth and vigor were detected. The incidence in the orchard was 3% (6 out of 200 trees) estimated by visual observation. Cross and longitudinal sections of the woody trunk of two trees were collected and examined, and an internal dark-brown discoloration to partial necrosis lesion was observed. To identify the causal agent, small pieces of wood from the edge of the symptomatic area were surface sterilized with 70% ethanol, rinsed twice with sterile distilled water, blotted on dry sterile filter paper, plated on potato dextrose agar (PDA) and incubated at 22°C. Fungal colonies were consistently isolated, and after 5 days, pure cultures were obtained by transferring mycelium to new PDA plates, preliminarily identified as Gnomoniopsis sp. (Visentin et al. 2012, Shuttleworth 2012). All cultures exhibited characteristics consistent with the description of G. castaneae (Syn. G. smithogilvyi), such as concentric development of greyish-brown mycelium, abundant stroma, hyaline conidia of 7.2 ±0.54 (6.1-8.1) X 2.3 ±0.26 (1.5-2.9) µm (n= 30), mainly biguttulate and fusoid. Total DNA was extracted, rDNA amplified using ITS1/ITS4 primers (White et al. 1990), and the fragment was Sanger sequenced and the sequence was deposited in GenBank (OR665735). BLAST analysis revealed a 99% identity to G. castaneae (MH384925). In addition, the DNA of the isolate was evaluated in a species-specific multiplex PCR (Silva-Campos et al. 2022), and the amplicons were electrophoretically separated, giving a similar band profile to G. smithogilvyi RGM 2903 and RGM 2904 strain from Chilean Collection of Microbial Genetic Resources. Pathogenicity of G. castaneae isolate (CV-11) was tested on ten replicates of 3-year-old C. sativa plants. Two wounds were made on the same season growing shoot and two on the previous season shoot. Longitudinal wounds (5 mm long, 4 mm wide and 2 mm depth) were made using a scalpel without removing the outer bark to inoculate the plants. Each wound was inoculated with a 5-mm mycelium plug, covered with the outer bark, and wrapped with Parafilm. Plugs of PDA were placed onto the wounds of two plants as control. The plants were kept in a growth chamber (22 ±1 0C and 90± 5% RH). All plants showed dark brown cankers measuring 20 to 40 mm long two weeks after inoculation. Also, most plants inoculated in the same season shoot presented wilted and chlorotic foliage. Mature conidiomata with cirri developed in most of the cankers. No symptoms were observed in the control. Fungal colonies of G. castaneae were reisolated on PDA from all inoculated chestnut plants and were not recovered from the controls. Recently, G. smithogilvyi has been identified as the causal agent of brown rot on chestnut nuts in Chile (Cisterna Oyarce et al. 2022); however, in several countries, it has also been associated as the causal agent of cankers in branch and stem of chestnut, as well as an endophyte in different hardwood species. Future studies on the incidence of this pathogen and its impact on chestnut yield should be carried out in the producing regions because it represents an emerging threat to Chilean chestnut production.
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BACKGROUND: Anemia-associated chronic kidney disease increases in more advanced stages with a subsequent acceleration in renal impairment progressing to end-stage renal disease. Although hepcidin and erythroferrone have been described as novel biomarkers of iron metabolism, there is still an area of ambiguity regarding iron utility in anemia-associated end-stage renal disease. OBJECTIVES: This study aims to determine the correlations between erythropoietin, erythroferrone, and hepcidin-25 in hemodialysis, and to evaluate the clinical utility of the hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness compared to reticulocyte maturation parameters. METHODS: Serum erythropoietin, erythroferrone, and hepcidin-25 levels in 35 dialysis-dependent patients on a maintenance dose of a short-acting erythropoiesis-stimulating agent were consequently assessed on Days 0, 5, and 7. The erythropoiesis activity was monitored by measuring the increment in reticulocyte maturation parameters. RESULTS: Though the effectiveness of erythropoiesis in these patients was not associated with the hepcidin-25/erythroferrone ratio, it was lower among those with effective erythropoiesis than those with ineffective erythropoiesis. The effective group showed a statistically significant increase in reticulocyte maturation parameters compared to the ineffective group. CONCLUSIONS: The findings show the pathogenesis of iron homeostasis in hemodialysis, the validity of hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness, and the advantageous monitoring of reticulocyte maturation measures to improve management of anemia-associated chronic kidney disease.
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Vasconcellea x heilbornii, known as babaco, is a hybrid native to Ecuador grown in small orchards in sub-tropical highland regions. Over the last decade, several viruses have been identified in babaco using high-throughput sequencing (HTS) (Cornejo-Franco et al. 2020, (Reyes-Proaño et al. 2023). In 2021, total RNA from a babaco plant showing distinctive leaf yellowing was extracted using the PureLink RNA Mini Kit (Thermo Fischer Scientific, USA) and subjected to HTS on an Illumina NovaSeq6000 system as 150 paired-end reads (Macrogen Inc., South Korea). Library construction was done using the TruSeq Stranded Total RNA Sample kit with Plant Ribo-Zero, as described (Villamor et al. 2022). Reads were processed using BBDuk and de novo assembled using SPAdes 3.15. both implemented in Geneious 2022. Contig analysis was done by BLASTx using the NCBI viral sequence database (as of November 2022). HTS generated 54 million reads, of which 12% assembled into contigs corresponding to genomes of previously reported babaco viruses including babaco virus Q (BabVQ), babaco nucleorhabdovirus 1 (BabRV1) and babaco ilarvirus 1 (BabIV1). Interestingly, 144 reads (0.0003%) assembled into seven contigs ranging from 100 to 480 nucleotides (nt) in length. These contigs showed homology, with 97% amino acid (aa) identity (100% query coverage), to regions of the RNA-dependent-RNA-polymerase (RdRp) of beet western yellows virus (BWYV, Acc. No. NC_004756), a member of the Polerovirus genus. To confirm the occurrence of BWYV in babaco, double-stranded RNA (dsRNA) was extracted from 15 g of leaf tissue from the original sample as described (Dodds et al. 1984) and used as template for reverse-transcription (RT)-PCR using overlapping primers designed to span all short contigs. RT-PCR amplified fragments were cloned into a pGEM®T-easy vector (Promega, USA) and sequenced by the Sanger method (Macrogen Inc., South Korea). The sequences were assembled into a single 2.7 kbp BWYV genome fragment comprising the complete protein 1 (P1) and partial RdRp gene (GenBank Acc. No. PP480670). Sequence alignments between the partially sequenced genome of the babaco isolate and its corresponding fragment from the closest BWYV isolate (NC_004756) revealed 94% and 97% identities at the nt and aa levels, respectively. To assess the prevalence of BWYV in babaco, 30 leaf samples showing yellowing symptoms from Pichincha (n=15) and Azuay (n=15) provinces were tested by RT-PCR using total RNA. Total RNA extraction and reverse transcription were done using the methodology described by Halgren et al. (2007). For RT-PCR, the primer set BWYV_Bab_F: 5'-CAGTGTCCTCCAAGTGCAACAT-3' / BWYV_Bab_R: 5'GGTTCCTTCCCAGTTTGGTGGT-3', which amplifies a 235 nt-long P1 region, was used. Three RT-PCR products from each positive sample were purified using the GeneJET PCR clean-up kit (Thermo Scientific, USA) and sequenced. BWYV was confirmed in 9 out of 15 samples (60%) from Pichincha, and in 10 out of 15 samples (64%) from Azuay. Samples were also tested for additional babaco viruses as described (Reyes-Proaño et al. 2023). All BWYV-infected plants turned out positive for papaya ringspot virus (PRSV), babaco mosaic virus (BabMV), BabVQ, and BabIV1. Hence, the impact of BWYV infection on babaco plants in single and mixed infections warrants further investigation. To the best of our knowledge, this is the first report of BWYV in a crop in Ecuador, and the first time it has been found in a Caricaceae species.
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Cultivation of yellow dragon fruit (Selenicereus megalanthus) in Peru has recently expanded (Verona-Ruiz et al. 2020). In August 2021, approximately 170 of 1,110 dragon fruit cuttings (15.3%) in the university's nursery (6°26'10'' S; 77°31'25'' W) showed basal rot symptoms. Initial symptoms included small brown spots on the base of stems, expanding towards the top that became soft and watery. All symptomatic plants eventually died, i.e., a severity of 100%. The disease was more prevalent on cuttings during the rooting phase than on well-established cuttings. We collected five symptomatic cuttings from throughout the nursery. Four sections of 1 × 1 cm2 of tissue adjacent to the diseased area were excised from each cutting, immersed for 1 min in 2% NaClO, rinsed twice with sterile distilled water, placed on potato dextrose agar (PDA) medium (four sections per Petri plate, five plates), and incubated at 25°C for 7 days. Morphologically similar mycelia grew from all sections, and five monosporic isolates were obtained, one per plate. Colonies grew fast, reaching 60 to 64 mm in 7 days, and produced violet-white cottony aerial mycelia with orange sporodochia on PDA, and abundant macro- and microconidia on synthetic nutrient-poor agar. Macroconidia were straight to slightly curved, typically with 2 to 3 septa, 16.6 to 23.3 × 1.7 to 3.7 µm (n = 30); microconidia were oval or kidney-shaped, and commonly hyaline, 6.7 to 16.4 × 2.5 to 4.7 µm (n = 40). Genomic DNA was extracted from isolate AFHP-100, then the ITS region and the TEF1 and RPB2 partial genes were amplified and sequenced (Accession numbers PP977433, OR437358, PP537149) following Gardes and Bruns (1993) and O'Donnell et al. (1998). We conducted a BLASTn search of ITS sequence against the NCBI "nr" database and local 'megablast' searches of TEF1 and RPB2 sequences against FUSARIUM-ID v.3.0 (Torres-Cruz et al. 2022). We found 100%, 98.19 to 99.84%, and 98.81 to 99.76% identities in ITS, TEF1, and RPB2 sequences, respectively, to the ex-epitype and other reference strains of Fusarium oxysporum (CBS 144134, NRRL26406, among others). A maximum likelihood phylogenetic analysis with a TEF1-RPB2 concatenated dataset with FUSARIUM-ID sequences also showed isolate AFHP-100 was F. oxysporum. A pathogenicity test was carried out by inoculating wounded healthy roots of three cuttings with submersion in a 5 × 106 conidia/ml suspension for 25 min. Then, the inoculated plants were planted in sterile soil. One cutting with wounded roots submerged in sterile water served as a control. In parallel, sterile soil was inoculated with 20 mL of the conidial suspension, and another three healthy cuttings were planted. A cutting planted in noninoculated soil also served as a control. Basal rot symptoms developed in all inoculated plants after 25 days. After re-isolation, the same fungus, corroborated based on micromorphology and TEF1 sequence (PP335689), was recovered, fulfilling Koch's postulates. The isolate was deposited in the KUELAP Herbarium (voucher KUELAP-3214), located and administered by the National University Toribio Rodriguez de Mendoza de Amazonas, in Chachapoyas, Peru. Fusarium oxysporum has been reported to cause basal stem rot in Bangladesh and Argentina (Mahmud et al. 2021; Wright et al. 2007), and stem blight in Malaysia (Mohd Hafifi et al. 2019) on dragon fruit. This is the first report of F. oxysporum causing basal rot in S. megalanthus in Peru. This fungus is among the most destructive plant pathogens, and the rapid expansion of the crop in Peru requires a comprehensive knowledge of the biotic factors influencing production. Therefore, this report is foundational to implementing proper control strategies.
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Introdução:A hipersensibilidade é uma doença que acomete grande parte da população que, por muitas vezes, também almejam uma melhor estética dos dentes através do clareamento e não alcançam seu objetivo devido sua condição sintomática.Objetivo:Verificar se uma paciente com hipersensibilidade dentinária e trincas no esmalte, ficaria sem dor após realização da blindagem do esmaltecom agentes dessensibilizantes de ação neural e oclusiva em sessão única e, ainda, se continuaria sem dor após o clareamento de consultório utilizando o peróxido de carbamida a 37%. Relato de caso:Paciente do sexo feminino, 31 anos, apresentava todos os elementos dentários com alta translucidez, muitas trincas e desgaste dental erosivo restrito à ponta de cúspide nos elementos 36 e 46. Após estes achados e associado àhistória clínica relatada de alta sensibilidade na dieta principalmente gelada, fechou-se o diagnóstico de um caso de hipersensibilidade dentinária. Foi realizado um procedimento dessensibilizante, em sessão única, com agentes de ação neural e oclusiva e, sequencialmente, clareamento dentário de consultório. A paciente relatou eliminação da sensibilidade com o tratamento dessensibilizante (blindagem do esmalte), o que levou àconcordância da paciente em realizar o clareamento com produto àbase de peróxido de carbamida a 37% que promete ausência de dor. Conclusões:o protocolo dessensibilizante utilizado cumpriu seu papel no quesito eliminação da dor com retorno da paciente às atividades diárias antes impossibilitadas (como ingerir bebidas geladas) e propiciou a realização de clareamento dentário sem dor, porém sem muito sucesso na mudança de cor alcançada (AU).
Introduction:Hypersensitivity is a disease that affects a large part of the population who, very often, also seek to improve the esthetics of their teeth through tooth bleaching and fail to achieve their goal due to their symptomatic condition.Objective:To ascertain whether a patient with dentin hypersensitivity and cracked enamel would be pain-free after enamel shielding with neuraland occlusive desensitizing agents in a single session, and whether she would continue to be pain-free after in-office tooth bleaching using 37% carbamide peroxide. Case report:A 31-year-old female patient who showcased high translucency in all dental elements, with many cracks and erosive tooth wear restricted to the cusp tips of elements 36 and 46. Following these findings and in association with the reported clinical history of high sensitivity, especially to cold diets, a diagnosis of dentin hypersensitivity was made. A single-session desensitizing procedure was carried out with neural and occlusive agents, and subsequently followed by in-office tooth bleaching. The patient reported the elimination of sensitivity with the desensitizing treatment (enamel shielding), which led to the patient agreeing to undergo teeth bleaching with a 37% carbamide peroxide-based product that guarantees no pain. Conclusions:The desensitizing protocol utilized fulfilled its role in terms of eliminating pain, with the patient returning to daily activities that had previously been impossible (such as drinking cold beverages) and allowing pain-free tooth bleaching to be carried out, but without much success in the color change achieved (AU).
Introducción: La hipersensibilidad es una enfermedad que afecta a gran parte de la población la cual, muchas veces, también pretende mejorar la estética de sus dientes a través del blanqueamiento y no alcanza su objetivo debido a su condición sintomática.Objetivo: Comprobar si una paciente con hipersensibilidad de la dentina y grietas en el esmalte estaría libre de dolor tras el blindaje del esmalte con agentes desensibilizantes neurales y oclusivos en una sola sesión, y, además, si seguiría estando libre de dolor tras el blanqueamiento dental en clínica utilizando peróxido de carbamida al 37%.Informe de caso: Una paciente de 31 años presentaba todos los elementos dentales con alta translucidez, con muchas grietas y desgaste dental erosivo restringido a las puntas de las cúspides de los elementos 36 y 46.Tras estos hallazgos y junto a la historia clínica descrita de alta sensibilidad especialmentefrente a una dieta fría, se realizó un diagnóstico de hipersensibilidad dentinaria. Se llevó a cabo un procedimiento de desensibilización en una sola sesión, con agentes neurales y oclusivos, seguido de un blanqueamiento dental clínico. La paciente declaró la eliminación de la sensibilidad con el tratamiento desensibilizante (blindaje del esmalte), lo que la llevó a aceptar el blanqueamiento con un producto a base de peróxido de carbamida al 37% que promete ser indoloro. Conclusiones: El protocolo de desensibilización utilizado cumplió su función en cuanto a la eliminación del dolor, permitiendo que la paciente volviera a realizar actividades cotidianas que antes le resultaban imposibles (como tomar bebidas frías) y permitiendo realizar el blanqueamiento dental sin dolor, pero sin mucho éxito en el cambio de color conseguido (AU).
Asunto(s)
Humanos , Femenino , Adulto , Blanqueamiento de Dientes , Esmalte Dental/anomalías , Sensibilidad de la Dentina/terapia , Desensibilizantes Dentinarios/uso terapéutico , DolorRESUMEN
The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC "Annex on Chemicals" some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman's assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed.