ABSTRACT
Propolis is a natural resinous mixture produced by honeybees with numerous biological activities. Considering the recently reported potential of propolis as an adjuvant in COVID-19 treatment, a methodology for the fractionation of the hexane extract of Brazilian green propolis (HEGP) was developed for the obtention of prenylated biomarkers by countercurrent chromatography. The inhibition of the interaction between the receptor binding domain (RBD) of spike and ACE2 receptor was evaluated by the Lumitáµá´¹ immunoassay. Fractionation of HEGP was performed by both normal (CCC1 and CCC2, with extended elution) and reversed (CCC3) phase elution-extrusion modes with the solvent system hexane-ethanol-water 4:3:1. The normal elution mode of CCC1 (471 mg HEGP in a 80 mL column volume, 1.6 mm id) was scaled-up (CCC5, 1211 mg HEGP in a 112 mL column volume, 2.1 mm id), leading to the isolation of 89.9 mg of artepillin C, 1; 52.7 mg of baccharin, 2; and 26.6 mg of chromene, with purities of 93 %, 83 % and 88 %, respectively, by HPLC-PDA. Among the isolated compounds, artepillin C, 1, and baccharin, 2, presented the best results in the Lumitáµá´¹ immunoassay, showing 67% and 51% inhibition, respectively, at the concentration of 10 µM. This technique proved to be of low operational cost and excellent reproducibility.
ABSTRACT
The study of wasp venoms has captured attention due to the presence of a wide variety of active compounds, revealing a diverse array of biological effects. Among these compounds, certain antimicrobial peptides (AMPs) such as mastoparans and chemotactic peptides have emerged as significant players, characterized by their unique amphipathic short linear alpha-helical structure. These peptides exhibit not only antibiotic properties but also a range of other biological activities, which are related to their ability to interact with biological membranes to varying degrees. This review article aims to provide updated insights into the structure/function relationships of AMPs derived from wasp venoms, linking this knowledge to the potential development of innovative treatments against infections.
Subject(s)
Antimicrobial Peptides , Wasp Venoms , Wasp Venoms/pharmacology , Wasp Venoms/chemistry , Peptides/chemistryABSTRACT
Bacterial inoculants have been used in agriculture to improve plant performance. However, laboratory and field requirements must be completed before a candidate can be employed as an inoculant. Therefore, this study aimed to evaluate the parameters for inoculant formulation and the potential of Bacillus subtilis (B70) and B. pumilus (B32) to improve phosphorus availability in maize (Zea mays L.) crops. In vitro experiments assessed the bacterial ability to solubilize and mineralize phosphate, their adherence to roots, and shelf life in cassava starch (CS), carboxymethyl cellulose (CMC), peat, and activated charcoal (AC) stored at 4 °C and room temperature for 6 months. A field experiment evaluated the effectiveness of strains to increase the P availability to plants growing with rock phosphate (RP) and a mixture of RP and triple superphosphate (TS) and their contribution to improving maize yield and P accumulation in grains. The B70 was outstanding in solubilizing RP and phytate mineralization and more stable in carriers and storage conditions than B32. However, root adherence was more noticeable in B32. Among carriers, AC was the most effective for preserving viable cell counts, closely similar to those of the initial inoculum of both strains. Maize productivity using the mixture RPTS was similar for B70 and B32. The best combination was B70 with RP, which improved the maize yield (6532 kg ha-1) and P accumulation in grains (15.95 kg ha-1). Our results indicated that the inoculant formulation with AC carrier and B70 is a feasible strategy for improving phosphorus mobilization in the soil and maize productivity.
Subject(s)
Bacillus , Phosphates , Phosphates/metabolism , Bacillus/metabolism , Plant Roots/microbiology , Phosphorus/metabolism , Bacillus subtilis/metabolism , Soil , Zea mays/microbiologyABSTRACT
Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.
ABSTRACT
Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.
ABSTRACT
Introduction: This randomized clinical trial aimed to determine whether the XP-endo finisher combined with or without foraminal enlargement has any significant effect on the incidence and intensity of postoperative pain in necrotic pulps. Materials and Methods: Clinical pain levels were measured after 6, 12, 24, 48, and 72 hours and at 7 postoperative days. All treatments were performed by an endodontist in a single visit. One hundred and twenty patients were included. All patients had a single tooth treated. The patients were divided into four groups: No FE (None Foraminal Enlargement) (n=30), FE (Foraminal Enlargement) (n=30), No FE+XPF (None Foraminal Enlargement+XP-endo Finisher) (n=30) and XPF+FE (XP-endo Finisher and Foraminal Enlargement) (n=30). The canals were irrigated with sodium hypochlorite, shaped using WaveOne Gold Medium file, and then filled by using a matching single cone and AH-Plus sealer. The cavity was filled using glass ionomer cement. Pain intensity was assessed using the visual analog scale. The data were analyzed with the ANOVA and Games-Howell test. The significance level was 5%. Results: The XPF+FE group experienced a higher level of pain, being classified on the visual analog scale as moderate for 48 postoperative hours and mild for 7 postoperative days (P<0.05). In the other groups, the pain was mild, only with different time intervals (P>0.05). Conclusions: Foraminal enlargement associated with XP-endo Finisher may cause moderate postoperative pain.
ABSTRACT
We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)-6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets.
Subject(s)
Actin-Related Protein 2-3 Complex , Actins , Humans , Actin-Related Protein 2-3 Complex/genetics , Actin-Related Protein 2-3 Complex/metabolism , Actins/genetics , Actins/metabolism , Cell Movement , Germ-Line Mutation , Cytokines/geneticsABSTRACT
COVID-19 primarily affects the respiratory system and can cause changes in other systems. Early identification of patients with a higher potential for complications is critical to provide the best possible treatment to reduce the disease's lethality. This study aimed to analyze the behavior of hematologic biomarkers in predicting mortality in patients hospitalized with COVID-19. This retrospective cohort study used data from the medical records of patients hospitalized with COVID-19 between March and August 2020 in two referral hospitals for treatment of the disease in the city of Cuiabá (in the state of Mato Grosso, Brazil). Clinical and laboratory characteristics related to cardiovascular involvement and death during hospitalization were evaluated. Neutrophils, lymphocytes, and monocytes, as well as the neutrophil-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MRL), were used as potential biomarkers of death. A total of 199 patients were included (male: 113; mean age: 51.4 years). Leukocyte, neutrophil, and lymphocyte counts showed a statistically significant association with death, as did NLR and MRL. Satisfactory accuracy in predicting death was observed for leukocyte, neutrophil, lymphocyte, NLR, and MLR counts. The hematologic biomarkers studied may be useful for prognosticating hospitalized patients for the possibility of death from COVID-19.
ABSTRACT
Throughout evolution, plants have developed a highly complex defense system against different threats, including phytopathogens. Plant defense depends on constitutive and induced factors combined as defense mechanisms. These mechanisms involve a complex signaling network linking structural and biochemical defense. Antimicrobial and pathogenesis-related (PR) proteins are examples of this mechanism, which can accumulate extra- and intracellular space after infection. However, despite their name, some PR proteins are present at low levels even in healthy plant tissues. When they face a pathogen, these PRs can increase in abundance, acting as the first line of plant defense. Thus, PRs play a key role in early defense events, which can reduce the damage and mortality caused by pathogens. In this context, the present review will discuss defense response proteins, which have been identified as PRs, with enzymatic action, including constitutive enzymes, ß-1,3 glucanase, chitinase, peroxidase and ribonucleases. From the technological perspective, we discuss the advances of the last decade applied to the study of these enzymes, which are important in the early events of higher plant defense against phytopathogens.
ABSTRACT
Rationale: the use of anti-TNFα therapy, such as Infliximab (IFX), in patients with Chron's disease (CD) can lead to changes in body composition. Objective: to evaluate the body composition and functional capacity of patients with CD. Method: Cross-sectional study with patients with CD in clinical remission using IFX. For anthropometric evaluation, it was measured: weight, height and waist circumference; functional capacity by the hand grip strength test and body composition by bioelectric impedance. After that, the fat-free mass index and body fat index were calculated. Continouns variables were analyzed by Pearson or Spearman coefficient. For the multiple linear regression model, the time of use of IFX was used as a dependent variable and waist circumference, fat-free mass index, phase angle and handgrip strength were used as independent variables. Results: forty-three patients were evaluated, with an average of 43.1± 13.5 years of age. Of the total, 44.2% were overweight and 44.2% had increased waist circumference, 58.1% were classified with high to very high fat-free mass, 30.2% were below the adequacy parameter for fat-free mass index and 11.6% had reduced functional capacity. Conclusion: overweight, as well as increased waist circumference and body fat, is common in CD patients in clinical remission using Infliximab. Most patients had preserved functional capacity, however there wasn't association with time of use of IFX.
Introdução: o uso de terapia anti-TNFα, como o Infliximabe (IFX), em pacientes com doença de Chron (DC) pode levar a alterações na composição corporal. Objetivo: avaliar a composição corporal e capacidade funcional de pacientes com DC. Metodologia: estudo transversal com pacientes com DC em remissão clínica, em uso de IFX. Foi realizada avaliação antropométrica (peso, estatura e circunferência da cintura); avaliação de capacidade funcional (teste de força de pressão manual); e avaliação de composição corporal (impedância bioelétrica) com cálculo do índice de massa livre de gordura e índice de gordura corporal. Variáveis contínuas foram analisadas pelo coeficiente de correlação de Pearson ou Spearman. Para o modelo de regressão linear múltipla, o tempo de uso do IFX foi utilizado como variável dependente e circunferência da cintura, índice de massa magra, ângulo de fase e força de preensão manual foram utilizados como variáveis independentes. Resultados: foram avaliados 43 pacientes, com média de idade de 43,1± 13,5 anos. 44,2% estavam acima do peso e 44,2% possuíam circunferência da cintura aumentada, 58,1% foram classificados com índice de gordura corporal de alto a muito alto, 30,2% estavam abaixo do parâmetro de adequação para o índice de massa livre de gordura e 11,6% apresentaram capacidade funcional reduzida. Conclusão: o excesso de peso e o aumento de circunferência da cintura e gordura corporal é frequente em pacientes com DC em remissão clínica e em uso de IFX. A maioria dos pacientes apresentou capacidade funcional preservada, porém não houve associação com o tempo de uso do IFX.
Subject(s)
Humans , Male , Female , Adult , Body Composition , Crohn Disease , Muscle Strength , Infliximab , Anthropometry , Cross-Sectional StudiesABSTRACT
Due to inadequate treatment and incorrect management, wastewater with dyes has a great toxic potential as an environmental liability, representing a major concern. In this context, this work aims to investigate the potential application of nanostructured powdery systems (nanocapsules and liposomes) in the photodegradation of Rhodamine B (RhB) dye, under UV and visible irradiation. Curcumin nanocapsules and liposomes containing ascorbic acid and ascorbyl palmitate were prepared, characterized, and dried using the spray drying technique. The drying processes of the nanocapsule and the liposome showed yields of 88% and 62%, respectively, and, after aqueous resuspension of the dry powders, it was possible to recover the nanocapsule size (140 nm) and liposome size (160 nm). The dry powders were characterized by Fourier transform infrared spectroscopy (FTIR), N2 physisorption at 77 K, X-ray diffraction (XRD), and diffuse reflectance spectroscopy (DRS-UV). Under UV irradiation, 64.8% and 58.48% of RhB were removed with nanocapsules and liposomes, respectively. While under visible radiation, nanocapsules and liposomes were able to degrade 59.54% and 48.79% of RhB, respectively. Under the same conditions, commercial TiO2 showed degradation of 50.02% (UV) and 42.14% (visible). After 5 cycles of reuse, there was a decrease of about 5% for dry powders under UV irradiation and 7.5% under visible irradiation. Therefore, the nanostructured systems developed have potential application in heterogeneous photocatalysis for the degradation of organic pollutants, such as RhB, as they demonstrated superior photocatalytic performance to commercial catalysts (nanoencapsulated curcumin > ascorbic acid and ascorbyl palmitate liposomal > TiO2).
Subject(s)
Curcumin , Nanocapsules , Powders , Coloring Agents , Liposomes , Ascorbic AcidABSTRACT
OBJECTIVES: Primary objectives were to analyze the prevalence of obstructive sleep apnea in (1) boys and girls, and (2) severe asthma versus moderate and mild cases. The authors hypothesized that girls and severe asthma would have a higher prevalence of obstructive sleep apnea. METHODS: Cross-sectional evaluation of asthmatic children attending a tertiary Pediatric Pulmonology clinic. The authors performed a history, physical examination, pulmonary function test, and home sleep apnea test. RESULTS: The authors studied 80 consecutive patients, 7-18 years old, mean age of 11.6 years (standard deviation 2.7), 51.3% female, and 18.5% obese. Pulmonary function tests were obtained from 80 volunteers, 45% with obstruction pattern. Home sleep apnea tests were available from 76 volunteers, with a mean obstructive respiratory index of 1.8 events/h. Obstructive sleep apnea was found in 49 volunteers (61.2%). The authors did not find associations between obstructive sleep apnea and sex or asthma severity. CONCLUSIONS: Obstructive sleep apnea was frequent among these asthmatic children. Sex and asthma severity were not risk factors. Considering the interrelationship of both diseases, it is worth keeping in mind the possibility of obstructive sleep apnea among children and teenagers with asthma.
Subject(s)
Asthma , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Male , Adolescent , Humans , Child , Female , Cross-Sectional Studies , Prevalence , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/diagnosis , Asthma/complications , Asthma/epidemiology , Risk FactorsABSTRACT
Abstract Objectives: Primary objectives were to analyze the prevalence of obstructive sleep apnea in (1) boys and girls, and (2) severe asthma versus moderate and mild cases. The authors hypothesized that girls and severe asthma would have a higher prevalence of obstructive sleep apnea. Methods: Cross-sectional evaluation of asthmatic children attending a tertiary Pediatric Pulmonology clinic. The authors performed a history, physical examination, pulmonary function test, and home sleep apnea test. Results: The authors studied 80 consecutive patients, 7-18 years old, mean age of 11.6 years (standard deviation 2.7), 51.3% female, and 18.5% obese. Pulmonary function tests were obtained from 80 volunteers, 45% with obstruction pattern. Home sleep apnea tests were available from 76 volunteers, with a mean obstructive respiratory index of 1.8 events/h. Obstructive sleep apnea was found in 49 volunteers (61.2%). The authors did not find associations between obstructive sleep apnea and sex or asthma severity. Conclusions: Obstructive sleep apnea was frequent among these asthmatic children. Sex and asthma severity were not risk factors. Considering the interrelationship of both diseases, it is worth keeping in mind the possibility of obstructive sleep apnea among children and teenagers with asthma.
ABSTRACT
A morte materna pode ser classificada como diretas e indiretas, são resultantes de complicações obstétricas no decorrer da gestação, durante o parto e/ou no puerpério. Em 2020, com a eclosão da pandemia do coronavírus se tornou um grande obstáculo para a garantir a saúde materno-fetal. No contexto brasileiro, eliminar significativamente a mortalidade por fatores evitáveis é um imenso desafio da saúde pública, bem como da equidade social, de gênero e de raça. Considerando os efeitos da COVID-19 no Brasil este trabalho objetivou analisar a tendência da RMM no Brasil antes e após a pandemia, no período de 2019 a 2021. Foi realizado um estudo ecológico descritivo e quantitativo analítico da razão de mortalidade materna (RMM) no Brasil, construído mediante dados secundários de estatísticas vitais extraídos do Sistema de Informações sobre Nascidos Vivos (Sinasc) e do Sistema de Informações sobre Mortalidade (SIM) - Datasus, no período de 2019 a 2021. Os dados do SIM e do Sinasc, até o ano 2021, são considerados finalizados. No período estudado, contabilizaram-se no total 6.571 óbitos maternos no Brasil. De acordo com os dados estatísticos, em 2019, 2020 e 2021 foram notificados 1.576, 1.965 e 3.030 óbitos maternos ao SIM, respectivamente. Em 2020 e 2021, mostrou em todas as regiões um elevado números de óbitos maternos em relação a 2019. Ainda, em 2021 apresentou maior número de óbitos em comparação a 2020. Foi observado um aumento significativo da RMM no Brasil em 2020 e 2021, em decorrência da epidemia de covid-19. As causas indiretas foram as mais prevalentes relacionadas aos óbitos maternos. Por fim, as altas taxas de mortalidade materna no Brasil evidenciam a necessidade de efetiva aplicação de políticas públicas a fim de potencializar a redução dos óbitos maternos no País.
Maternal death can be classified as direct and indirect, they are consequences of obstetric complications during pregnancy, during delivery and/or in the puerperium. In 2020, with the outbreak of the coronavirus pandemic, it became a major obstacle to ensuring maternal and fetal health. In the Brazilian context, significantly eliminating mortality from preventable factors is an immense public health challenge, as well as social, gender and racial equity. Considering the effects of COVID-19 in Brazil, this work aimed to analyze the trend of MMR in Brazil before and after the pandemic, from 2019 to 2021. An ecological descriptive and quantitative analytical study of the maternal mortality ratio (MMR) was carried out in the Brazil, constructed using secondary statistical data extracted from the Information System on Live Births (Sinasc) and the Mortality Information System (SIM) - Datasus, from 2019 to 2021. Data from SIM and Sinasc, up to the year 2021, are considered completed. In the observed period, a total of 6,571 maternal deaths were recorded in Brazil. According to statistical data, in 2019, 2020 and 2021, 1,576, 1,965 and 3,030 maternal deaths were reported to the SIM, respectively. In 2020 and 2021, it showed a high number of maternal deaths in all regions compared to 2019. Also, in 2021 it showed a higher number of deaths compared to 2020. A significant increase in MMR was observed in Brazil in 2020 and 2021, in as a result of the covid-19 epidemic. Indirect causes were the most prevalent related to maternal deaths. Finally, the high maternal mortality rates in Brazil highlight the need for effective implementation of public policies in order to enhance the reduction of maternal deaths in the country.
La muerte materna puede ser clasificada como directa e indirecta, son consecuencias de complicaciones obstétricas durante el embarazo, durante el parto y/o en el puerperio. En 2020, con el estallido de la pandemia por coronavirus, se convirtió en un gran obstáculo para garantizar la salud materna y fetal. En el contexto brasileño, eliminar significativamente la mortalidad por factores prevenibles es un inmenso desafío de salud pública, así como de equidad social, de género y racial. Considerando los efectos de la COVID-19 en Brasil, este trabajo tuvo como objetivo analizar la tendencia de la TMM en Brasil antes y después de la pandemia, de 2019 a 2021. Se realizó un estudio ecológico descriptivo y cuantitativo analítico de la razón de mortalidad materna (RMM) en el Brasil, construido a partir de datos estadísticos secundarios extraídos del Sistema de Información sobre Nacidos Vivos (Sinasc) y del Sistema de Información sobre Mortalidad (SIM) - Datasus, de 2019 a 2021. Los datos del SIM y del Sinasc, hasta el año 2021, se consideran completos. En el período observado, se registraron un total de 6.571 muertes maternas en Brasil. Según los datos estadísticos, en 2019, 2020 y 2021, se notificaron al SIM 1.576, 1.965 y 3.030 muertes maternas, respectivamente. En 2020 y 2021, mostró un alto número de muertes maternas en todas las regiones en comparación con 2019. Asimismo, en 2021 mostró un mayor número de muertes en comparación con 2020. Se observó un aumento significativo de la RMM en Brasil en 2020 y 2021, en como resultado de la epidemia de covid-19. Las causas indirectas fueron las más prevalentes relacionadas con las muertes maternas. Por último, las altas tasas de mortalidad materna en Brasil ponen de relieve la necesidad de una aplicación eficaz de las políticas públicas con el fin de mejorar la reducción de las muertes maternas en el país.
ABSTRACT
Pancreatic islet beta cells are essential for maintaining glucose homeostasis. To understand the impact of aging on beta cells, we performed meta-analysis of single-cell RNA sequencing datasets, transcription factor (TF) regulon analysis, high-resolution confocal microscopy, and measured insulin secretion from nondiabetic donors spanning most of the human life span. This revealed the range of molecular and functional changes that occur during beta cell aging, including the transcriptional deregulation that associates with cellular immaturity and reorganization of beta cell TF networks, increased gene transcription rates, and reduced glucose-stimulated insulin release. These alterations associate with activation of endoplasmic reticulum (ER) stress and autophagy pathways. We propose that a chronic state of ER stress undermines old beta cell structure function to increase the risk of beta cell failure and type 2 diabetes onset as humans age.
ABSTRACT
Gossypium hirsutum L. represents the best cotton species for fiber production, thus computing the largest cultivated area worldwide. Meloidogyne incognita is a root-knot nematode (RKN) and one of the most important species of Meloidogyne genus, which has a wide host range, including cotton plants. Phytonematode infestations can only be partially controlled by conventional agricultural methods, therefore, more effective strategies to improve cotton resistance to M. incognita disease are highly desirable. The present study employed functional genomics to validate the involvement of two previously identified candidate genes, encoding dirigent protein 4-GhDIR4 and peroxiredoxin-2-GhPRXIIB, in cotton defense against M. incognita. Transgenic A. thaliana plant lines overexpressing GhDIR4 and GhPRXIIB genes were generated and displayed significantly improved resistance against M. incognita infection in terms of female nematode abundance in the roots when compared to wild-type control plants. For our best target-gene GhDIR4, an in-silico functional analysis, including multiple sequence alignment, phylogenetic relationship, and search for specific protein motifs unveiled potential orthologs in other relevant crop plants, including monocots and dicots. Our findings provide valuable information for further understanding the roles of GhDIR and GhPRXIIB genes in cotton defense response against RKN nematode. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03282-4.
ABSTRACT
AIMS: Synthetic glucocorticoids, including dexamethasone (DEX), are clinically prescribed due to their immunoregulatory properties. In excess they can perturb glucose homeostasis, with individuals predisposed to glucose intolerance more sensitive to these negative effects. While DEX is known to negatively impact ß-cell function, it is unclear how. Hence, our aim was to investigate the effect of DEX on ß-cell function, both alone and in combination with a diabetogenic milieu in the form of elevated glucose and palmitate. MAIN METHODS: Human pancreatic EndoC-ßH1 cells were cultured in the presence of high glucose and palmitate (glucolipotoxicity) and/or a pharmacological concentration of DEX, before functional and molecular analyses. KEY FINDINGS: Either treatment alone resulted in reduced insulin content and secretion, while the combination of DEX and glucolipotoxicity promoted a strong synergistic effect. These effects were associated with reduced insulin biosynthesis, likely due to downregulation of PDX1, MAFA, and the proinsulin converting enzymes, as well as reduced ATP response upon glucose stimulation. Genome-wide DNA methylation analysis found changes on PDE4D, MBNL1 and TMEM178B, all implicated in ß-cell function, after all three treatments. DEX alone caused very strong demethylation of the glucocorticoid-regulated gene ZBTB16, also known to influence the ß-cell, while the combined treatment caused altered methylation of many known ß-cell regulators and diabetes candidate genes. SIGNIFICANCE: DEX treatment and glucolipotoxic conditions separately alter the ß-cell epigenome and function. The combination of both treatments exacerbates these changes, showing that caution is needed when prescribing potent glucocorticoids in patients with dysregulated metabolism.
Subject(s)
Glucocorticoids , Insulin-Secreting Cells , Adenosine Triphosphate/metabolism , Dexamethasone/metabolism , Dexamethasone/toxicity , Epigenome , Glucocorticoids/metabolism , Glucocorticoids/pharmacology , Glucose/metabolism , Humans , Insulin/metabolism , Insulin-Secreting Cells/metabolism , Palmitates/pharmacology , Proinsulin/metabolism , Proinsulin/pharmacologyABSTRACT
We investigated the near-field distribution associated to the photonic mode of terahertz photonic micro-resonators by scattering scanning near-field optical microscopy. Probing individual THz micro-resonators concentrating electric fields is important for high-sensitivity chemical and biochemical sensing and fundamental light-matter interactions studies at the nanoscale. We imaged both electric field concentration predicted by numerical simulations and unexpected patterns that deviate from intuitive assumptions. We propose a scenario based on the combination of the near-field with the far-field pattern of the probe/resonator ensemble that is in excellent agreement with the experimental data and propose an image analysis procedure to recover the near-field of such structures.