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1.
Am J Trop Med Hyg ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744272

RESUMO

Nontyphoidal Salmonella is one of the major causes of self-limiting diarrheal disease and the most common foodborne pathogen worldwide. It is an important contributor to the burden of foodborne illness in South America, including Peru, where chicken and pork are important vehicles for Salmonella infection. Salmonella infections are underreported, particularly in low- and middle-income countries where concerted action tackling Salmonella along the chicken and pork chains, from primary production to retail, is urgently needed. To support and inform the implementation of new strategies to reduce Salmonella contamination of chicken and pork, this study describes the frequency and distribution of foodborne outbreaks attributed to Salmonella in Peru and evaluates the level of Salmonella in chicken and pork meat sold in markets of three regions of Peru. To that end, we analyzed historical reports of foodborne outbreaks, levels of Salmonella in chicken and pork sold in markets, and the number of mesophiles in the collected meat samples. As a result, the microbiological analysis reveals a widespread contamination of chicken (77.1%) and pork (26.8%) with Salmonella. It also pinpoints Salmonella as the causative agent in nearly half of the outbreaks (47.0%) where the potential origin is identified over a 11-year period with chicken, mayonnaise, and pork being the most likely food vehicles. These results suggest that Salmonella is a major contributor to foodborne illness in Peru and that the monitoring of mesophiles could be a good strategy for surveillance, generating data to support source attribution studies and ultimately evidence-informed policies.

2.
J Environ Qual ; 53(3): 287-299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38453688

RESUMO

Enhanced efficiency fertilizers (EEFs) can reduce nitrogen (N) losses in temperate agriculture but are less effective in the tropics. We aimed to design a new EEF and evaluate their performance in simple-to-complex tests with tropical soils and crops. We melt-extruded urea at different loadings into biodegradable polymer matrix composites using biodegradable polyhydroxyalkanoate (PHA) or polybutylene adipate-co-terephthalate (PBAT) polymers with urea distributed throughout the pellet. These contrast with commercially coated EEF that have a polymer-coated urea core. We hypothesized that matrix fertilizers would have an intermediate N release rate compared to fast release from urea or slow release from coated EEF. Nitrogen release rates in water and sand-soil columns confirmed that the matrix fertilizer formulations had a more progressive N release than a coated EEF. A more complex picture emerged from testing sorghum [Sorghum bicolor (L.) Moench] grown to maturity in large soil pots, as the different formulations resulted in minor differences in plant N accumulation and grain production. This confirms the need to consider soil interactions, microbial processes, crop physiology, and phenology for evaluating fertilizer performance. Promisingly, crop δ15N signatures emerged as an integrated measure of efficacy, tracking likely N conversions and losses. The three complementary evaluations combine the advantages of standardized high-throughput screening and more resource-intensive and realistic testing in a plant-soil system. We conclude that melt-blended biodegradable polymer matrix fertilizers show promise as EEF because they can be designed toward more abiotically or more microbially driven N release by selecting biopolymer type and N loading rate.


Assuntos
Agricultura , Fertilizantes , Nitrogênio , Polímeros , Fertilizantes/análise , Nitrogênio/análise , Agricultura/métodos , Solo/química , Biodegradação Ambiental , Sorghum
4.
New Phytol ; 240(4): 1405-1420, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37705460

RESUMO

Atmospheric conditions are expected to become warmer and drier in the future, but little is known about how evaporative demand influences forest structure and function independently from soil moisture availability, and how fast-response variables (such as canopy water potential and stomatal conductance) may mediate longer-term changes in forest structure and function in response to climate change. We used two tropical rainforest sites with different temperatures and vapour pressure deficits (VPD), but nonlimiting soil water supply, to assess the impact of evaporative demand on ecophysiological function and forest structure. Common species between sites allowed us to test the extent to which species composition, relative abundance and intraspecific variability contributed to site-level differences. The highest VPD site had lower midday canopy water potentials, canopy conductance (gc ), annual transpiration, forest stature, and biomass, while the transpiration rate was less sensitive to changes in VPD; it also had different height-diameter allometry (accounting for 51% of the difference in biomass between sites) and higher plot-level wood density. Our findings suggest that increases in VPD, even in the absence of soil water limitation, influence fast-response variables, such as canopy water potentials and gc , potentially leading to longer-term changes in forest stature resulting in reductions in biomass.


Assuntos
Folhas de Planta , Solo , Solo/química , Folhas de Planta/fisiologia , Floresta Úmida , Pressão de Vapor , Água/fisiologia , Abastecimento de Água , Transpiração Vegetal/fisiologia , Árvores/fisiologia
5.
Sci Total Environ ; 905: 167161, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730068

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated that Wastewater Based Epidemiology is a fast and economical alternative for monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the community level in high-income countries. In the present study, wastewater from a city in the Peruvian Highlands, which lacks a wastewater treatment plant, was monitored for one year to assess the relationship between the concentration of SARS-CoV-2 and the reported cases of COVID-19 in the community. Additionally, we compared the relationship between rotavirus (RV), norovirus genogroup II (NoV GGII), and human adenovirus (HAdV) with the number of reported cases of acute gastroenteritis. Before commencing the analysis of the samples, the viral recovery efficacy of three processing methods was determined in spiked wastewater with SARS-CoV-2. This evaluation demonstrated the highest recovery rate with direct analysis (72.2 %), as compared to ultrafiltration (50.8 %) and skimmed milk flocculation (5.6 %). Wastewater monitoring revealed that 72 % (36/50) of the samples tested positive for SARS-CoV-2, with direct analysis yielding the highest detection frequency and quantification of SARS-CoV-2. Furthermore, a strong correlation was observed between the concentration of SARS-CoV-2 in wastewater and the reported cases of COVID-19, mainly when we shift the concentration of SARS-CoV-2 by two weeks, which allows us to anticipate the onset of the fourth and fifth waves of the pandemic in Peru up to two weeks in advance. All samples processed using the skimmed milk flocculation method tested positive and showed high concentrations of RV, NoV GGII, and HAdV. In fact, the highest RV concentrations were detected up to four weeks before outbreaks of acute gastroenteritis reported in children under four years of age. In conclusion, the results of this study suggest that periodic wastewater monitoring is an excellent epidemiological tool for surveillance and can anticipate outbreaks of infectious diseases, such as COVID-19, in low- and middle-income countries.


Assuntos
Adenovírus Humanos , COVID-19 , Gastroenterite , Norovirus , Rotavirus , Criança , Humanos , Pré-Escolar , SARS-CoV-2 , COVID-19/epidemiologia , Peru/epidemiologia , Águas Residuárias , Gastroenterite/epidemiologia , Surtos de Doenças , Genótipo
6.
Am J Trop Med Hyg ; 109(3): 568-570, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37487566

RESUMO

Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a food and waterborne pathogen with severe public health implications. We report the first-time isolation of this pathogen in the Central Highlands of Peru through standardized culture procedures and polymerase chain reaction (PCR). Escherichia coli strains were cultured from rectal-anal swabs from dairy calves and beef from food markets. The latex agglutination test was used to detect O157 and H7 antigens, and multiplex real-time PCR was carried out to detect virulence-related genes. The STEC O157:H7 strains were isolated from 3.5% (1/28) of beef samples and from 6.0% (3/50) of dairy calves that also carried both eaeA and stx1 genes. Therefore, this pathogen is a potential cause of food/waterborne disease in the region, and its surveillance in both livestock and their products should be improved to characterize the impact of its zoonotic transmission. From 2010 to 2020, E. coli was suspected in 10 outbreaks reported to the Peruvian Ministry of Health. Isolates from future outbreaks should be characterized to assess the burden posed by STEC O157:H7 in Peru.


Assuntos
Escherichia coli O157 , Microbiologia de Alimentos , Carne Vermelha , Escherichia coli O157/genética , Escherichia coli O157/isolamento & purificação , Escherichia coli O157/patogenicidade , Carne Vermelha/microbiologia , Fezes/microbiologia , Animais , Bovinos , Indústria de Laticínios , Peru , Reação em Cadeia da Polimerase , Testes de Fixação do Látex , Fatores de Virulência/genética
7.
Biofouling ; 39(2): 145-156, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36971265

RESUMO

Empirical knowledge of natural plant extracts is increasingly proving to be a promising field. The effect of Calendula officinalis L. (CO) and Capsicum annum (CA) glycolic extracts (GlExt) have potential that should be further developed in microbial tests. The effect of CO-GlExt and CA-GlExt was evaluated on eight multidrug-resistant clinical strains of Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as collection strains for each bacterial. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract were determined in comparison with 0.12% chlorhexidine. The tests were performed on single species biofilms, at 5 min and 24 h, using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The MIC and MBC of the extract ranged from 1.56 to 50 mg mL-1 for all strains evaluated. Analysis of the MTT assay revealed a strong antimicrobial potential of CA-GlExt, comparable to chlorhexidine. The findings suggest that CA-GlExt is effective against multidrug-resistant strains of K. pneumoniae and P. aeruginosa in planktonic state and biofilms.


Assuntos
Calendula , Capsicum , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Klebsiella pneumoniae , Glicóis/farmacologia , Clorexidina/farmacologia , Plâncton , Biofilmes , Mentol/farmacologia , Cânfora/farmacologia , Extratos Vegetais/farmacologia , Testes de Sensibilidade Microbiana
8.
Sci Rep ; 12(1): 15446, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104446

RESUMO

The liver is among the few organs having the ability to self-regenerate in response to a severe damage compromising its functionality. The Aryl hydrocarbon receptor (Ahr) is a transcription factor relevant for the detoxification of xenobiotics but also largely important for liver development and homeostasis. Hence, liver cell differentiation is developmentally modulated by Ahr through the controlled expression of pluripotency and stemness-inducing genes. Here, 2/3 partial hepatectomy (PH) was used as a clinically relevant approach to induce liver regeneration in Ahr-expressing (Ahr+/+) and Ahr-null (Ahr-/-) mice. Ahr expression and activity were early induced after 2/3 PH to be gradually downmodulated latter during regeneration. Ahr-/- mice triggered liver regeneration much faster than AhR+/+ animals, although both reached full regeneration at the latest times. At initial stages after PHx, earlier regenerating Ahr-/- livers had upregulation of cell proliferation markers and increased activation of signalling pathways related to stemness such as Hippo-YAP and Wnt/ß-catenin, concomitantly with the induction of pro-inflammatory cytokines TNFa, IL6 and p65. These phenotypes, together with the improved metabolic adaptation of Ahr-/- mice after PHx and their induced sustained cell proliferation, could likely result from the expansion of undifferentiated stem cells residing in the liver expressing OCT4, SOX2, KLF4 and NANOG. We propose that Ahr needs to be induced early during regeneration to fine-tune liver regrowth to physiological values. Since Ahr deficiency did not result in liver overgrowth, its transient pharmacological inhibition could serve to improve liver regeneration in hepatectomized and transplanted patients and in those exposed to damaging liver toxins and carcinogens.


Assuntos
Regeneração Hepática , Receptores de Hidrocarboneto Arílico , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diferenciação Celular , Hepatectomia , Fígado/metabolismo , Fígado/cirurgia , Camundongos , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo
9.
JMIR Mhealth Uhealth ; 10(9): e35727, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066926

RESUMO

BACKGROUND: Wearables and their benefits for the safety and well-being of users have been widely studied and have had an enormous impact on the general development of these kinds of devices. Yet, the extent of research into the use and impact of wearable devices in the underwater environment is comparatively low. In the past 15 years, there has been an increased interest in research into wearables that are used underwater, as the use of such wearables has steadily grown over time. However, there has so far been no clear indication in the literature about the direction in which efforts for the design and construction of underwater wearable devices are developing. Therefore, the analysis presented in this scoping review establishes a good and powerful basis for the further development and orientation of current underwater wearables within the field. OBJECTIVE: In this scoping review, we targeted wearable devices for underwater use to make a comprehensive map of their capabilities and features and discuss the general direction of the development of underwater wearables and the orientation of research into novel prototypes of these kinds of devices. METHODS: In September 2021, we conducted an extensive search for existing literature on 4 databases and for grey literature to identify developed prototypes and early-stage products that were described and tested in water, could be worn and interacted with (eg, displays, buttons, etc), and were fully functional without external equipment. The studies were written in English, came from peer-reviewed academic sources, and were published between 2005 and 2021. We reviewed each title and abstract. The data extraction process was carried out by one author and verified by another author. RESULTS: In total, 36 relevant studies were included. Among these, 4 different categories were identified; 18 studies dealt primarily with safety devices, 9 dealt with underwater communication devices, 7 dealt with head-up displays, and 2 dealt with underwater human-computer interaction approaches. Although the safety devices seemed to have gained the most interest at the time of this study, a clear trend toward underwater communication wearables was identified. CONCLUSIONS: This review sought to provide a first insight into the possibilities and challenges of the technologies that have been used in and for wearable devices that are meant for use in the underwater environment. Among these, underwater communication technologies have had the most significant influence on future developments. Moreover, a topic that has not received enough attention but should be further addressed is human-computer interaction. By developing underwater wearables that cover 2 or more of the technology categories that we identified, the extent of the benefits of such devices can be significantly increased in the future.


Assuntos
Mergulho , Dispositivos Eletrônicos Vestíveis , Humanos , Tecnologia
10.
Aging (Albany NY) ; 14(10): 4281-4304, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35619220

RESUMO

Aging impairs organismal homeostasis leading to multiple pathologies. Yet, the mechanisms and molecular intermediates involved are largely unknown. Here, we report that aged aryl hydrocarbon receptor-null mice (AhR-/-) had exacerbated cellular senescence and more liver progenitor cells. Senescence-associated markers ß-galactosidase (SA-ß-Gal), p16Ink4a and p21Cip1 and genes encoding senescence-associated secretory phenotype (SASP) factors TNF and IL1 were overexpressed in aged AhR-/- livers. Chromatin immunoprecipitation showed that AhR binding to those gene promoters repressed their expression, thus adjusting physiological levels in AhR+/+ livers. MCP-2, MMP12 and FGF secreted by senescent cells were overproduced in aged AhR-null livers. Supporting the relationship between senescence and stemness, liver progenitor cells were overrepresented in AhR-/- mice, probably contributing to increased hepatocarcinoma burden. These AhR roles are not liver-specific since adult and embryonic AhR-null fibroblasts underwent senescence in culture, overexpressing SA-ß-Gal, p16Ink4a and p21Cip1. Notably, depletion of senescent cells with the senolytic agent navitoclax restored expression of senescent markers in AhR-/- fibroblasts, whereas senescence induction by palbociclib induced an AhR-null-like phenotype in AhR+/+ fibroblasts. AhR levels were downregulated by senescence in mouse lungs but restored upon depletion of p16Ink4a-expressing senescent cells. Thus, AhR restricts age-induced senescence associated to a differentiated phenotype eventually inducing resistance to liver tumorigenesis.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina , Receptores de Hidrocarboneto Arílico , Envelhecimento/metabolismo , Animais , Senescência Celular/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Fibroblastos/metabolismo , Fígado/metabolismo , Camundongos , Receptores de Hidrocarboneto Arílico/genética
11.
Front Cell Dev Biol ; 10: 884004, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465323

RESUMO

Transcription factor aryl hydrocarbon receptor (AHR) has emerged as one of the main regulators involved both in different homeostatic cell functions and tumor progression. Being a member of the family of basic-helix-loop-helix (bHLH) transcriptional regulators, this intracellular receptor has become a key member in differentiation, pluripotency, chromatin dynamics and cell reprogramming processes, with plenty of new targets identified in the last decade. Besides this role in tissue homeostasis, one enthralling feature of AHR is its capacity of acting as an oncogene or tumor suppressor depending on the specific organ, tissue and cell type. Together with its well-known modulation of cell adhesion and migration in a cell-type specific manner in epithelial-mesenchymal transition (EMT), this duality has also contributed to the arise of its clinical interest, highlighting a new potential as therapeutic tool, diagnosis and prognosis marker. Therefore, a deregulation of AHR-controlled pathways may have a causal role in contributing to physiological and homeostatic failures, tumor progression and dissemination. With that firmly in mind, this review will address the remarkable capability of AHR to exert a different function influenced by the phenotype of the target cell and its potential consequences.

12.
Front Cell Dev Biol ; 10: 841548, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372341

RESUMO

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promising drug with promyelinating properties. Clemastine penetrates the blood brain barrier efficiently and promotes remyelination in different animal models of neurodegeneration including multiple sclerosis, ischemia and Alzheimer's disease. However, its role in myelination during development is unknown. We showed that clemastine treatment during development increased oligodendrocyte differentiation in both white and gray matter. However, despite the increase in the number of oligodendrocytes, conduction velocity of myelinated fibers of corpus callosum decreased in clemastine treated mice. Confocal and electron microscopy showed a reduction in the number of myelinated axons and nodes of Ranvier and a reduction of myelin thickness in corpus callosum. To understand the mechanisms leading to myelin formation impairment in the presence of an excess of myelinating oligodendrocytes, we focused on microglial cells that also express muscarinic M1 receptors. Importantly, the population of CD11c+ microglia cells, necessary for myelination, as well as the levels of insulin growth factor-1 decrease in clemastine-treated mice. Altogether, these data suggest that clemastine impact on myelin development is more complex than previously thought and could be dependent on microglia-oligodendrocyte crosstalk. Further studies are needed to clarify the role of microglia cells on developmental myelination.

13.
PLoS One ; 17(3): e0264898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35286329

RESUMO

Taenia solium is an important cause of acquired epilepsy worldwide and remains endemic in Asia, Africa, and Latin America. Transmission of this parasite is still poorly understood despite the design of infection experiments to improve our knowledge of the disease, with estimates for critical epidemiological parameters, such as the probability of human-to-pig infection after exposure to eggs, still lacking. In this paper, a systematic review was carried out and eight pig infection experiments were analyzed to describe the probability of developing cysts. These experiments included different pathways of inoculation: with ingestion of proglottids, eggs, and beetles that ingested eggs, and direct injection of activated oncospheres into the carotid artery. In these experiments, different infective doses were used, and the numbers of viable and degenerated cysts in the body and brain of each pig were registered. Five alternative dose-response models (exponential, logistic, log-logistic, and exact and approximate beta-Poisson) were assessed for their accuracy in describing the observed probabilities of cyst development as a function of the inoculation dose. Dose-response models were developed separately for the presence of three types of cysts (any, viable only, and cysts in the brain) and considered for each of the four inoculation methods ("Proglottids", "Eggs", "Beetles" and "Carotid"). The exact beta-Poisson model best fit the data for the three types of cysts and all relevant exposure pathways. However, observations for some exposure pathways were too scarce to reliably define a dose-response curve with any model. A wide enough range of doses and sufficient sample sizes was only found for the "Eggs" pathway and a merged "Oral" pathway combining the "Proglottids", "Eggs" and "Beetles" pathways. Estimated parameter values from this model suggest that a low infective dose is sufficient to result in a 50% probability for the development of any cyst or for viable cyst infections. Although this is a preliminary model reliant on a limited dataset, the parameters described in this manuscript should contribute to the design of future experimental infections related to T. solium transmission, as well as the parameterization of simulation models of transmission aimed at informing control.


Assuntos
Besouros , Cisticercose , Cistos , Doenças dos Suínos , Taenia solium , Animais , Cisticercose/epidemiologia , Suínos , Doenças dos Suínos/epidemiologia
14.
Stem Cell Reports ; 16(9): 2351-2363, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34478649

RESUMO

Mammalian embryogenesis is a complex process controlled by transcription factors that regulate the balance between pluripotency and differentiation. Transcription factor aryl hydrocarbon receptor (AhR) regulates OCT4/POU5F1 and NANOG, both essential controllers of pluripotency, stemness and early embryo development. Molecular mechanisms controlling OCT4/POU5F1 and NANOG during embryogenesis remain unidentified. We show that AhR regulates pluripotency factors and maintains the metabolic activity required for proper embryo differentiation. AhR-lacking embryos (AhR-/-) showed a pluripotent phenotype characterized by a delayed expression of trophectoderm differentiation markers. Accordingly, central pluripotency factors OCT4/POU5F1 and NANOG were overexpressed in AhR-/- embryos at initial developmental stages. An altered intracellular localization of these factors was observed in the absence of AhR and, importantly, Oct4 had an opposite expression pattern with respect to AhR from the two-cell stage to blastocyst, suggesting a negative regulation of OCT4/POU5F by AhR. We propose that AhR is a regulator of pluripotency and differentiation in early mouse embryogenesis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular/genética , Desenvolvimento Embrionário/genética , Receptores de Hidrocarboneto Arílico/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Embrião de Mamíferos , Metabolismo Energético , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Genótipo , Glicólise , Via de Sinalização Hippo , Camundongos , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Estresse Oxidativo , Transporte Proteico , Receptores de Hidrocarboneto Arílico/metabolismo
15.
Front Psychiatry ; 12: 671223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504441

RESUMO

Functional Analytic Psychotherapy (FAP) offers a radically behavioral and transdiagnostic conception of the formation of the "self" and the appearance of a diversity of psychological problems. This study examined the extent to which a wide variety of psychological disorders (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility/aggressiveness, phobic anxiety, paranoid ideation, and psychoticism) and a global index of psychopathological severity may in fact be linked to problems of the "self" according to the FAP conception. Two questionnaires, one related to self-experience according to FAP and the other to find the scores on several different psychopathology scales, were administered to 280 adult Spaniards for this purpose. The results confirmed the transdiagnostic nature of the "self"-experience. There are significant and strong correlations between all the psychopathology scales studied and self-experience. Linear regression analyses also show that, along with age and gender, in some cases, the score on self-experience predicts each and every one of the psychopathological variables studied, in addition to the Global Severity Index. These results are discussed and related to the transdiagnostic approach to psychopathology.

16.
Cancers (Basel) ; 13(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34439225

RESUMO

Non-small cell lung adenocarcinoma (NSCLC) bearing K-RasG12D mutations is one of the most prevalent types of lung cancer worldwide. Aryl hydrocarbon receptor (AHR) expression varies in human lung tumors and has been associated with either increased or reduced lung metastasis. In the mouse, Ahr also adjusts lung regeneration upon injury by limiting the expansion of resident stem cells. Here, we show that the loss of Ahr enhances K-RasG12D-driven NSCLC in mice through the amplification of stem cell subpopulations. Consistent with this, we show that K-RasG12D;Ahr-/- lungs contain larger numbers of cells expressing markers for both progenitor Clara (SCGB1A1 and CC10) and alveolar type-II (SFTPC) cells when compared to K-RasG12D;Ahr+/+-driven tumors. They also have elevated numbers of cells positive for pluripotent stem cells markers such as SOX2, ALDH1, EPCAM, LGR5 and PORCN. Typical pluripotency genes Nanog, Sox2 and c-Myc were also upregulated in K-RasG12D;Ahr-/- lung tumors as found by RNAseq analysis. In line with this, purified K-RasG12D/+;Ahr-/- lung cells generate larger numbers of organoids in culture that can subsequently differentiate into bronchioalveolar structures enriched in both pluripotency and stemness genes. Collectively, these data indicate that Ahr antagonizes K-RasG12D-driven NSCLC by restricting the number of cancer-initiating stem cells. They also suggest that Ahr expression might represent a good prognostic marker to determine the progression of K-RasG12D-positive NSCLC patients.

17.
São José dos Campos; s.n; 2021. 62 p. graf, tab.
Tese em Português | LILACS, BBO - Odontologia | ID: biblio-1362540

RESUMO

O conhecimento dos efeitos dos extratos naturais de plantas vem cada vez mais se mostrando um campo promissor. Extratos de Calendula officinalis, Capsicum annuum e Hamamelis virginiana apresentam propriedades analgésicas, anti-inflamatórias, antioxidantes e potencial antimicrobiano que deve ser aprofundado. Assim, o objetivo foi avaliar ação antimicrobiana dos extratos glicólicos em culturas planctônicas e biofilmes de cepas padrão e clínicas de Klebsiella pneumoniae e Pseudomonas aeruginosa. Foi realizado o teste de microdiluição em caldo segundo Clinical and Laboratory Standards Institute, para determinação da Concentração Inibitória Mínima (CIM) e Concentração Microbicida Mínima (CMM) dos extratos. Foram realizados biofilmes monotípicos, nos tempos de contato de 5 min e 24 h, utilizando o teste de MTT. A CIM e CMM variaram de 1,56 a 50 mg/mL para todas as cepas avaliadas. C. annuum (50 mg/mL) apresentou redução de 0,25% entre 8,60% para cepa ATCC de P. aeruginosa (5 min) e em 24 h redução de 99,89% entre 99,99%, destacando-se os extratos de C. annuum (100 mg/mL) e os de C. officinalis. C. annuum (200 mg/mL) apresentou redução de 18% de K. pneumoniae (ATCC 4352). Em 24 h houve redução de 8,86%-75,74%, para o extrato de C. annuum (100 mg/mL). Os extratos apresentaram resultados mais satisfatórios quando expostos aos tratamentos de 24 horas. As cepas clínicas K1, K2 e K3 responderam ao tratamento de C. annuum (50 e 100 mg/mL) (p>0,05%). Para cepa clínica K4, os extratos de C. annuum (50 e 100 mg/mL) e C. officinalis (12,5 mg/mL) promoveram redução de viabilidade semelhante a clorexidina 2% (p>0,05%). O extrato de C. annuum (50 e 100 mg/mL), promoveu a redução de viabilidade de P1 e P2, enquanto o extrato de C. officinalis (25 e 50 mg/mL), reduziu P1 (p>0,05%). Para as cepas P3 e P4 o extrato de 50 e 100 mg/mL de C. annuum, apresentaram resultados semelhantes a clorexidina. Conclui-se que todos os extratos apresentaram ação antimicrobiana em cultura planctônica, no entanto, o extrato de C. annuum foi o que apresentou importante ação antibiofilme (24 h) sobre cepas clínicas multirresistentes de K. pneumoniae e P. aeruginosa, podendo ser considerado um potencial agente antimicrobiano.


Empirical knowledge of natural plant extracts is increasingly proving to be a promising field. Extracts of Calendula officinalis, Capsicum annuum and Hamamelis virginiana have analgesic, anti-inflammatory, antioxidant and antimicrobial potential that should be further developed. This research objective was to evaluate the antimicrobial action of glycolic extracts in planktonic cultures and biofilms of standard and clinical strains of Klebsiella pneumoniae and Pseudomonas aeruginosa. The broth microdilution test was performed according to the Clinical and Laboratory Standards Institute, to determine the Minimum Inhibitory Concentration (MIC) and Minimum Microbicide Concentration (MMC) of the extracts. Tests were performed on monotypic biofilms, at contact times of 5 min and 24 h, using the MTT test. The MIC and CMM of the extracts ranged from 1.56 to 50 mg/mL for all strains evaluated. C. annuum (50 mg/mL) showed a reduction of 0.25% between 8.60% for the ATCC strain of P. aeruginosa (5 min) and in 24 h a reduction of 99.89% between 99.99%, highlighting extracts from C. annuum (100 mg/mL) and from C. officinalis. C. annuum (200 mg/mL) showed an 18% reduction in K. pneumoniae (ATCC 4352). In 24 h there was a reduction of 8.86% between 75.74% for the extract of C. annuum (100 mg/mL). The extracts showed more satisfactory results when exposed to 24-hour treatments. Clinical strains K1, K2 and K3 responded to the treatment of C. annuum (50 and 100 mg/mL) (p>0.05%). For clinical strain K4, extracts of C. annuum (50 and 100 mg/mL) and C. officinalis (12.5 mg/mL) promoted a reduction in viability similar to chlorhexidine 2% (p>0.05%). The extract of C. annuum (50 and 100 mg/mL), reduced the viability of P1 and P2, while the extract of C. officinalis (25 and 50 mg/mL), reduced P1 (p>0.05% ). For strains P3 and P4, the extract of 50 and 100 mg/mL of C. annuum showed similar results to chlorhexidine. It is concluded that all extracts showed antimicrobial action in planktonic cultures, however, the extract of C. annuum was the one that showed an important antibiofilm action (24 h) on multiresistant clinical strains of K. pneumoniae and P. aeruginosa and can be considered a potential antimicrobial agent


Assuntos
Extratos Vegetais , Testes de Sensibilidade Microbiana , Biofilmes , Analgésicos , Anti-Infecciosos , Pseudomonas aeruginosa , Capsicum , Hamamelis , Klebsiella pneumoniae
18.
Int. j interdiscip. dent. (Print) ; 13(3): 181-185, dic. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1385170

RESUMO

RESUMEN: Introducción: El recubrimiento pulpar directo es un método para tratar la pulpa vital expuesta conservando su vitalidad. Tradicionalmente se ha utilizado el hidróxido de calcio como material de elección para este tratamiento, sin embargo, sus efectos adversos han promovido el desarrollo y utilización de agregado trióxido mineral (MTA), del cual aún existe controversia sobre una mayor efectividad. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos cuatro revisiones sistemáticas que en conjunto incluyeron siete estudios primarios, de los cuales, cuatro corresponden a ensayos aleatorizados. Concluimos que el recubrimiento directo con agregado trióxido mineral (MTA) comparado con hidróxido de calcio probablemente aumenta el éxito clínico y que podría aumentar la sobrevida pulpar, pero la certeza de la evidencia es baja.


ABSTRACT: Introduction: Direct pulp capping has been suggested as the treatment of exposed vital pulp. Conventionally calcium hydroxide (CH) has been the main biomaterial option for maintaining pulp vitality, but its adverse effects have promoted the development and use of mineral trioxide aggregate (MTA). However, there is still uncertainty regarding its effectiveness. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified four systematic reviews including seven studies overall, of which four were randomized trials. We conclude that direct pulp capping with mineral trioxide aggregate (MTA) probably improves clinical success rate and may improve pulp survival rate, however, the certainty of the evidence has been assessed as low.


Assuntos
Humanos , Hidróxido de Cálcio/administração & dosagem , Silicatos/administração & dosagem , Compostos de Cálcio/administração & dosagem , Compostos de Alumínio/administração & dosagem , Dentição Permanente , Cárie Dentária/terapia , Capeamento da Polpa Dentária/métodos , Óxidos , Tomada de Decisões , Combinação de Medicamentos , Agentes de Capeamento da Polpa Dentária e Pulpectomia
19.
Tree Physiol ; 40(6): 810-821, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32159813

RESUMO

Conifers are, for the most part, competitively excluded from tropical rainforests by angiosperms. Where they do occur, conifers often occupy sites that are relatively infertile. To gain insight into the physiological mechanisms by which angiosperms outcompete conifers in more productive sites, we grew seedlings of a tropical conifer (Podocarpus guatemalensis Standley) and an angiosperm pioneer (Ficus insipida Willd.) with and without added nutrients, supplied in the form of a slow-release fertilizer. At the conclusion of the experiment, the dry mass of P. guatemalensis seedlings in fertilized soil was approximately twofold larger than that of seedlings in unfertilized soil; on the other hand, the dry mass of F. insipida seedlings in fertilized soil was ~20-fold larger than seedlings in unfertilized soil. The higher relative growth rate of F. insipida was associated with a larger leaf area ratio and a higher photosynthetic rate per unit leaf area. Higher overall photosynthetic rates in F. insipida were associated with an approximately fivefold larger stomatal conductance than in P. guatemalensis. We surmise that a higher whole-plant hydraulic conductance in the vessel bearing angiosperm F. insipida enabled higher leaf area ratio and higher stomatal conductance per unit leaf area than in the tracheid bearing P. guatemalensis, which enabled F. insipida to capitalize on increased photosynthetic capacity driven by higher nitrogen availability in fertilized soil.


Assuntos
Ficus , Magnoliopsida , Traqueófitas , Fotossíntese , Folhas de Planta , Solo
20.
Ann Neurol ; 87(5): 670-676, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32052483

RESUMO

OBJECTIVE: Antibodies against neuronal N-methyl-D-aspartate receptors (NMDARs) in patients with anti-NMDAR encephalitis alter neuronal synaptic function and plasticity, but the effects on other cells of the nervous system are unknown. METHODS: Cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis (preabsorbed or not with GluN1) and a human NMDAR-specific monoclonal antibody (SSM5) derived from plasma cells of a patient, along the corresponding controls, were used in the studies. To evaluate the activity of oligodendrocyte NMDARs and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in vitro after exposure to patients' CSF antibodies or SSM5, we used a functional assay based on cytosolic Ca2+ imaging. Expression of the glucose transporter (GLUT1) in oligodendrocytes was assessed by immunocytochemistry. RESULTS: NMDAR agonist responses were robustly reduced after preincubation of oligodendrocytes with patients' CSF or SSM5 but remained largely unaltered with the corresponding controls. These effects were NMDAR specific, as patients' CSF did not alter responses to AMPA receptor agonists and was abrogated by preabsorption of CSF with HEK cells expressing GluN1 subunit. Patients' CSF also reduced oligodendrocyte expression of glucose transporter GLUT1 induced by NMDAR activity. INTERPRETATION: Antibodies from patients with anti-NMDAR encephalitis specifically alter the function of NMDARs in oligodendrocytes, causing a decrease of expression of GLUT1. Considering that normal GLUT1 expression in oligodendrocytes and myelin is needed to metabolically support axonal function, the findings suggest a link between antibody-mediated dysfunction of NMDARs in oligodendrocytes and the white matter alterations reported in patients with this disorder. ANN NEUROL 2020;87:670-676.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/metabolismo , Autoanticorpos/imunologia , Oligodendroglia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Adolescente , Adulto , Animais , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/farmacologia , Autoantígenos/imunologia , Células Cultivadas , Criança , Feminino , Transportador de Glucose Tipo 1/biossíntese , Humanos , Masculino , Oligodendroglia/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/imunologia , Adulto Jovem
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