RESUMO
BACKGROUND: Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated colorectal cancer (CAC) with poor prognosis. IBD etiology remains undefined but involves environmental factors, genetic predisposition, microbiota imbalance (dysbiosis) and mucosal immune defects. Mesenchymal stromal cell (MSC) injections have shown good efficacy in reducing intestinal inflammation in animal and human studies. However, their effect on tumor growth in CAC and their capacity to restore gut dysbiosis are not clear. METHODS: The outcome of systemic administrations of in vitro expanded human intestinal MSCs (iMSCs) on tumor growth in vivo was evaluated using the AOM/DSS model of CAC in C57BL/6J mice. Innate and adaptive immune responses in blood, mesenteric lymph nodes (MLNs) and colonic tissue were analyzed by flow cytometry. Intestinal microbiota composition was evaluated by 16S rRNA amplicon sequencing. RESULTS: iMSCs significantly inhibited colitis and intestinal tumor development, reducing IL-6 and COX-2 expression, and IL-6/STAT3 and PI3K/Akt signaling. iMSCs decreased colonic immune cell infiltration, and partly restored intestinal monocyte homing and differentiation. iMSC administration increased the numbers of Tregs and IFN-γ+CD8+ T cells in the MLNs while decreasing the IL-4+Th2 response. It also ameliorated intestinal dysbiosis in CAC mice, increasing diversity and Bacillota/Bacteroidota ratio, as well as Akkermansia abundance, while reducing Alistipes and Turicibacter, genera associated with inflammation. CONCLUSION: Administration of iMSCs protects against CAC, ameliorating colitis and partially reverting intestinal dysbiosis, supporting the use of MSCs for the treatment of IBD.
Assuntos
Neoplasias Associadas a Colite , Colite , Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Neoplasias Associadas a Colite/complicações , Neoplasias Associadas a Colite/patologia , Interleucina-6 , Camundongos Endogâmicos C57BL , Disbiose/complicações , Linfócitos T CD8-Positivos , RNA Ribossômico 16S , Fosfatidilinositol 3-Quinases , Colite/patologia , Inflamação , Colo/patologia , Doenças Inflamatórias Intestinais/patologia , Imunidade , Sulfato de Dextrana , Modelos Animais de DoençasRESUMO
BACKGROUND High altitude increases sunlight exposure, resulting in actinic keratosis, which predisposes people to skin cancer. The dermoscopy procedure evaluates keratotic and pigmented skin changes. This study aimed to describe the clinical and dermoscopic actinic changes in the lips of 25 indigenous children living at high altitude in Ecuador. MATERIAL AND METHODS An observational study was conducted in a public school in the Andes region of Ecuador (August-November 2019). Twenty-five children, males and females, age 5-15 years were assessed by complete physical examination, digital dermoscopic photographs, and punch biopsies. Descriptive statistics and Fisher's exact test were used to summarize and analyze the data. RESULTS We included 17 (68%) boys and 8 (32%) girls with a mean age of 9.8±2.0 years. Clinical lips findings reported desquamation [52% Upper Lip (UL); 40% Lower Lip (LL)], fissuring (8% UL; 8% LL), scabs (8% UL; 8% LL), and discoloration (40% UL; 20% LL). Dermoscopic features included a white-yellow lip color (24% UL; p=0.02). The main morphologic pattern of blood vessels was monomorphic (88% UL; p<0.001), polymorphous (60% LL; p<0.001), dotted pattern (64% UL; 28% LL; p=0.02), and linear-irregular (32% UL; 72% LL; p=0.01). Girls had radiating white structures on UL (p=0.025), while boys presented white structureless areas (UL 63.6%; LL 77.8%; p=0.032). No differences in dermoscopic findings were observed according to Fitzpatrick scale score (FSS). Punch biopsies showed no indications of actinic cheilitis. CONCLUSIONS Dermoscopic features in indigenous children living in high altitudes were related to actinic damage, but histopathological findings were negative.
Assuntos
Ceratose Actínica , Neoplasias Cutâneas , Masculino , Feminino , Humanos , Criança , Pré-Escolar , Adolescente , Lábio , Altitude , Equador , Neoplasias Cutâneas/patologia , Ceratose Actínica/diagnóstico , Ceratose Actínica/patologiaRESUMO
The impact of food literacy (FL) and nutrition literacy (NL) programs on lifestyles and health is recognized in the literature, yet few studies systematize it. This study aims to deepen the understanding of FL/NL from the characterization of programs in terms of (i) theoretical foundations, conceptualization and measuring instruments; (ii) characterization of the FL/NL programs and results and (iii) limitations and future directions declared. A scoping review of original articles addressing FL/NL programs from the Web of Science, Scopus and PubMed databases published between 2015 and 2023. There was a somewhat restricted view of the construct and the absence of a clear boundary between FL and NL. Half of the studies reported theoretical foundations. The most used model was Social Cognitive Learning Theory. More significant development of programs was observed in Australia, using quasi-experimental designs. Most of the studies informed positive results. Limitations of the studies related to the sampling process, absence of a control group and lack of follow-up. It is suggested that long-term interventions consider economic, social and cultural factors. Despite that theoretical and empirical aspects should be revised, FL/NL programs are a suitable strategy to mitigate the social and health effects of inadequate nutrition.
Assuntos
Alimentos , Estado Nutricional , Humanos , Aprendizagem , Austrália , Formação de ConceitoRESUMO
Natural products and secondary metabolites comprise an indispensable resource from living organisms that have transformed areas of medicine, agriculture, and biotechnology. Recent advances in high-throughput DNA sequencing and computational analysis suggest that the vast majority of natural products remain undiscovered. To accelerate the natural product discovery pipeline, cell-free metabolic engineering approaches used to develop robust catalytic networks are being repurposed to access new chemical scaffolds, and new enzymes capable of performing diverse chemistries. Such enzymes could serve as flexible biocatalytic tools to further expand the unique chemical space of natural products and secondary metabolites, and provide a more sustainable route to manufacture these molecules. Herein, we highlight select examples of natural product biosynthesis using cell-free systems and propose how cell-free technologies could facilitate our ability to access and modify these structures to transform synthetic and chemical biology.
Assuntos
Produtos Biológicos/metabolismo , Produtos Biológicos/química , Sequenciamento de Nucleotídeos em Larga Escala , Engenharia Metabólica , Estrutura MolecularRESUMO
Obesity is one of the main features of metabolic syndrome, where a low-grade chronic inflammation and gut dysbiosis contribute to the development of the related metabolic dysfunctions. Different probiotics have demonstrated beneficial effects on this condition, increasing the interest in the development of probiotic treatments. Lactobacillus fermentum CECT5716 has shown anti-inflammatory effects and capacity to modulate microbiota composition in different experimental models. In this study, L. fermentum CECT5716 was evaluated in a model of high fat diet-induced obesity in mice. It exerts anti-obesity effects, associated with its anti-inflammatory properties and amelioration of endothelial dysfunction and gut dysbiosis. The probiotic restores Akkermansia sp. abundance and reduced Erysipelotrichi class and Clostridium spp presence as well as increased Bacteroides proportion. In conclusion, this probiotic represents a very interesting approach. Our findings describe, for the first time, the ability of this probiotic to ameliorate experimental obesity through microbiome modulation, affecting different bacteria that have been reported to play a key role in the pathogenesis of obesity. Therefore, this suggests a potential use of L. fermentum CECT5716 in clinical practice, also taking into account that probiotic treatments have demonstrated to be relatively safe and well tolerated.
Assuntos
Disbiose/terapia , Microbioma Gastrointestinal , Limosilactobacillus fermentum , Obesidade/terapia , Probióticos/uso terapêutico , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/etiologia , Disbiose/metabolismo , Limosilactobacillus fermentum/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Probióticos/metabolismoRESUMO
PURPOSE: Probiotics have been shown to exert beneficial effects in IBD although their exact mechanisms are not completely understood. The aim of the present study was to assess the intestinal anti-inflammatory activity of different probiotics (Lactobacillus fermentum CECT5716, Lactobacillus salivarius CECT5713, Escherichia coli Nissle 1917, Saccharomyces boulardii CNCMI-745 in the dinitrobenzene sulfonic acid (DNBS) model of mouse colitis and correlate it with the modifications of the gut microbiota and the immune response, focusing on miRNA expression. METHODS: The probiotics were daily administered orally for 25 days. On day 19 colitis was induced by rectal installation of DNBS. At the end of the treatment, mice were sacrificed and the colonic damage was assessed biochemically by analysing the expression of different markers involved in the immune response, including miRNAs; and the colonic microbiota by pyrosequencing. Probiotics properties were also evaluated in vitro in different immune cell types (CMT-93 intestinal epithelial cells and bone marrow-derived macrophages), where the expression of different mRNAs and miRNAs was examined. RESULTS: All the probiotics displayed intestinal anti-inflammatory effects but slightly different, especially regarding miRNAs expression. Likewise, the probiotics ameliorated the colitis-associated dysbiosis, although showing differences in the main bacterial groups affected. CONCLUSION: Among the probiotics assayed, Lactobacillus fermentum CECT5716 and Escherichia coli Nissle 1917 appear to present the best intestinal anti-inflammatory effects, being the latter one of the few probiotics with reputed efficacy in human IBD. Therefore, Lactobacillus fermentum CECT5716 could be considered as a complementary nutritional strategy for IBD treatment.
Assuntos
Colite , Microbioma Gastrointestinal , MicroRNAs , Probióticos , Animais , Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Colite/terapia , Dinitrobenzenos/uso terapêutico , Camundongos , MicroRNAs/genética , Ácidos Sulfônicos/uso terapêuticoRESUMO
In crude extract-based cell-free protein synthesis (CFPS), DNA templates are transcribed and translated into functional proteins. Although linear expression templates (LETs) are less laborious and expensive to generate, plasmid templates are often desired over polymerase chain reaction-generated LETs due to increased stability and protection against exonucleases present in the extract of the reaction. Here we demonstrate that addition of a double stranded DNA-binding protein to the CFPS reaction, termed single-chain Cro protein (scCro), achieves terminal protection of LETs. This CroP-LET (scCro-based protection of LET) method effectively increases superfolder green fluorescent protein (sfGFP) expression levels from LETs in Escherichia coli CFPS reactions by sixfold. Our yields are comparable to other strategies that provide chemical and enzymatic DNA stabilization in E. coli CFPS. Notably, we also report that the CroP-LET method successfully enhanced yields in CFPS platforms derived from nonmodel organisms. Our results show that CroP-LET increased sfGFP yields by 18-fold in the Vibrio natriegens CFPS platform. With the fast-expanding applications of CFPS platforms, this method provides a practical and generalizable solution to protect linear expression DNA templates.
Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Escherichia coli/química , Escherichia coli/química , Proteínas de Fluorescência Verde/biossíntese , Vibrio/química , Sistema Livre de Células , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/genética , Plasmídeos , Vibrio/metabolismoRESUMO
Fumaria genus has been traditionally used for managing inflammatory and gastrointestinal disorders. The study evaluates the immunomodulatory potential of the total alkaloid fraction from Fumaria capreolata L. (AFC) in primary macrophages and the intestinal anti-inflammatory effect in a dextran sodium sulphate-induced colitis in mice. AFC inhibited LPS-stimulated bone marrow-derived macrophages gene expression program dose-dependently. In vivo, AFC markedly reduced macroscopic and microscopic signs of intestinal inflammation. Besides, it restored the colonic expression of pro-inflammatory and anti-inflammatory mediators, as well as enhanced the expression of intestinal barrier markers. These results demonstrate the potential of AFC extract as a therapeutic tool for the management of inflammatory bowel disease.
Assuntos
Alcaloides/química , Anti-Inflamatórios/química , Colite/tratamento farmacológico , Fumaria/química , Doenças Inflamatórias Intestinais/tratamento farmacológico , Extratos Vegetais/química , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Intestinos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Extratos Vegetais/farmacologiaRESUMO
INTRODUCTION: Many studies have showed the beneficial effects of the olive (Olea europaea) leaf extract (OLE) in experimental models of metabolic syndrome, which have been ascribed to the presence of phenolic compounds, like oleuropeoside. This study evaluated the effects of a chemically characterized OLE in high fat diet (HFD)-induced obesity in mice, describing the underlying mechanisms involved in the beneficial effects, with special attention to vascular dysfunction and gut microbiota composition. METHODS: C57BL/6J mice were distributed in different groups: control, control-treated, obese and obese-treated with OLE (1, 10 and 25â¯mg/kg/day). Control mice received a standard diet, whereas obese mice were fed HFD. The treatment was followed for 5 weeks, and animal body weight periodically assessed. At the end of the treatment, metabolic plasma analysis (including lipid profile) as well as glucose and insulin levels were performed. The HFD-induced inflammatory status was studied in liver and fat, by determining the RNA expression of different inflammatory mediators by qPCR; also, different markers of intestinal epithelial barrier function were determined in colonic tissue by qPCR. Additionally, flow cytometry of immune cells from adipose tissue, endothelial dysfunction in aortic rings as well as gut microbiota composition were evaluated. Faecal microbiota transplantation (FMT) to antibiotic-treated mice fed with HFD was performed. RESULTS: OLE administration reduced body weight gain, basal glycaemia and insulin resistance, and showed improvement in plasma lipid profile when compared with HFD-fed mice. The extract significantly ameliorated the HFD-induced altered expression of key adipogenic genes, like PPARs, adiponectin and leptin receptor, in adipose tissue. Furthermore, the extract reduced the RNA expression of Tnf-α, Il-1ß, Il-6 in liver and adipose tissue, thus improving the tissue inflammatory status associated to obesity. The flow cytometry analysis in adipose tissue corroborated these observations. Additionally, the characterization of the colonic microbiota by sequencing showed that OLE administration was able to counteract the dysbiosis associated to obesity. The extract reversed the endothelial dysfunction observed in the aortic rings of obese mice. FMT from donors HFD-OLE to recipient mice fed an HFD prevented the development of obesity, glucose intolerance, insulin resistance and endothelial dysfunction. CONCLUSION: OLE exerts beneficial effects in HFD-induced obesity in mice, which was associated to an improvement in plasma and tissue metabolic profile, inflammatory status, gut microbiota composition and vascular dysfunction.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Disbiose/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Obesidade/tratamento farmacológico , Olea , Extratos Vegetais/uso terapêutico , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Citocinas/genética , Dieta Hiperlipídica , Disbiose/metabolismo , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Resistência à Insulina , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , Obesidade/metabolismo , Obesidade/microbiologia , Fitoterapia , Extratos Vegetais/farmacologia , Folhas de PlantaRESUMO
Cell-based assays are finding wider use in evaluating compounds in primary screens for drug development, yet it is still challenging to measure enzymatic activities as an end point in a cell-based assay. This paper reports a strategy that combines state-of-the-art cantilever free polymer pen lithography (PPL) with self-assembled monolayer laser desorption-ionization (SAMDI) mass spectrometry to guide cell localization and measure cellular enzymatic activities. Experiments are conducted with a 384 spot array, in which each spot is composed of â¼400 nanoarrays and each array has a 10 × 10 arrangement of 750 nm features that present extracellular matrix (ECM) proteins surrounded by an immobilized phosphopeptide. Cells attach to the individual nanoarrays, where they can be cultured and treated with small molecules, after which the media is removed and the cells are lysed. Phosphatase enzymes in the proximal lysate can then act on the immobilized phosphopeptide substrate to convert it to the dephosphorylated form. After the lysate is removed, the array is analyzed by SAMDI mass spectrometry to identify the extent of dephosphorylation and, therefore, the amount of enzyme activity in the cell. This novel approach of using nanopatterning to mediate cell adhesion and SAMDI to record enzyme activities in the proximal lysate will enable a broad range of cellular assays for applications in drug discovery and research not possible with conventional strategies.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Proteínas da Matriz Extracelular/química , Espectrometria de Massas/métodos , Nanoestruturas/química , Análise Serial de Tecidos/métodos , Avaliação Pré-Clínica de Medicamentos/instrumentação , Ensaios Enzimáticos/instrumentação , Ensaios Enzimáticos/métodos , Inibidores Enzimáticos/farmacologia , Desenho de Equipamento , Células HeLa , Humanos , Proteínas Imobilizadas/química , Espectrometria de Massas/instrumentação , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Análise Serial de Tecidos/instrumentaçãoRESUMO
MOTIVATION: TCS is a widely used haplotype network reconstruction software, but lacks the capability of overlapping genetic with geographic structure, which is often a first step in phylogeographic analysis. RESULTS: tcsBU is a web-based program that extends the capabilities of TCS, by implementing haplotype classification into an arbitrary user-defined scheme, which is displayed as pie-chart like graphs embedded into the network. Taking advantage of modern graphic libraries, tcsBU also improves the speed at which the final network layout is reached. Networks can be saved as a Scalable Vector Graphics format. AVAILABILITY AND IMPLEMENTATION: tcsBU is available on-line at http://cibio.up.pt/software/tcsBU/. The source code is freely available from https://github.com/sairum/tcsbu/ under a standard MIT license.
Assuntos
Haplótipos , Software , Gráficos por ComputadorRESUMO
On page 3811, M. Mrksich and co-workers culture cells using self-assembled monolayers presenting cell adhesion ligands and enzyme substrates. A lysis buffer disrupts the cell membranes, releasing enzymes that modify the immobilized substrates. These modifications can be measured with SAMDI mass spectrometry, giving a high-throughput, cell-based assay.
Assuntos
Ensaios de Triagem em Larga Escala/métodos , Espectrometria de Massas/métodos , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Cell-based, high-throughput screening (HTS) assays are increasingly important tools used in drug discovery, but frequently rely on readouts of gene expression or phenotypic changes and require development of specialized, labeled reporters. Here a cell-based, label-free assay compatible with HTS is introduced that can report quantitatively on enzyme activities by measuring mass changes of substrates with matrix-assisted laser desorption/ionization mass spectrometry. The assay uses self-assembled monolayers to culture cells on arrays presenting substrates, which serve as reporters for a desired enzyme activity. Each spot of cells is treated with a compound, cultured and lysed, enabling endogenous enzymes to act on the immobilized peptide substrate. It is demonstrated that the assay can measure protein tyrosine phosphatase (PTP) activity from as few as five cells and a screen is described that identifies a compound that reduces PTP activity in cell lysates. This approach offers a valuable addition to the methods available for cell-based screening.
Assuntos
Espectrometria de Massas/métodos , Enzimas/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Especificidade por SubstratoRESUMO
BACKGROUND: Chronic kidney disease (CKD) is a disorder with high morbidity and mortality worldwide whose complications generate multiple costs. In Ecuador, only a few healthcare institutions have implemented management protocols aimed to reduce costs and to improve the quality of life of patients. The aim of this study is to evaluate the short-term (1-year) and long-term (5-year) costs and savings in the management of secondary hyperparathyroidism (SHPT) of hemodialyzed CKD patients by comparing calcitriol and paricalcitol in a large social security hospital in Quito, Ecuador. METHODS: The estimation model assessed the resources used in the management of SHPT by comparing prospectively the cost savings within 1-year and 5-year time horizon with calcitriol and paricalcitol. Hospitalization, erythropoietin (EPO), treatment doses, intravenous iron consumption, and medical supplies were estimated according international references, based on the initial parathormone level (iPTH) of patients. The Ecuadorian National Reference costs (2014-2015) and institutional costs were used to calculate treatment costs. A statistical sensitivity analysis was also performed. RESULTS: The study was based on data from 354 patients of whom 147 (41.4 %) had a value of iPTH in the range 300-600 pg/ml, 45 (12.8 %) in the range 601-800 pg/ml, and 162 (45.7 %) over 800 pg/ml. The 1-year estimated costs per patient for calcitriol and paricalcitol, respectively, were: medication, 63.88 USD and 1,123.44 USD; EPO, 19,522.95 USD and 16,478 USD; intravenous iron 143.21 USD and 187.76 USD. Yearly hospitalization costs per patient were 11,647.99 USD with calcitriol and 8,019.41 USD with paricalcitol. Total yearly costs per patient amounted to 31,378.02 USD with calcitriol and 25,809.50 USD with paricalcitol. Total savings using paricalcitol were 5,568.52 USD per patient compared with calcitriol. The 5-year cumulative medication costs were 319 USD for calcitriol and 2,403 USD for paricalcitol; EPO with calcitriol was 97,615 USD and with paricalcitol 82,394 USD; intravenous iron with calcitriol was 716 USD and paricalcitol 939 USD. Hospitalization costs for patients with calcitriol and paricalcitol were 43,095 USD and 62,595 USD, respectively. Total savings using paricalcitol amounted 32,414 USD per patient compared with calcitriol. CONCLUSIONS: Paricalcitol use generated more cost savings than calcitriol after 1 and 5 years.
Assuntos
Orçamentos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/economia , Falência Renal Crônica , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/economia , Calcitriol/administração & dosagem , Calcitriol/economia , Custos e Análise de Custo , Custos de Medicamentos , Equador , Ergocalciferóis/administração & dosagem , Ergocalciferóis/economia , Feminino , Hospitalização/economia , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Qualidade de Vida , Diálise Renal , Estudos RetrospectivosRESUMO
Immunomodulatory antibiotics have been proposed for the treatment of multifactorial conditions such as inflammatory bowel disease. Probiotics are able to attenuate intestinal inflammation, being considered as safe when chronically administered. The aim of the study was to evaluate the anti-inflammatory effects of doxycycline, a tetracycline with immunomodulatory properties, alone and in association with the probiotic Saccharomyces boulardii CNCMI-745. Doxycycline was assayed both in vitro (Caco-2 epithelial cells and RAW 264.7 macrophages) and in vivo, in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis and the dextran sodium sulfate (DSS) model of mouse colitis. In addition, the anti-inflammatory effect of the association of doxycycline and the probiotic was evaluated in vitro and in vivo in a DSS model of reactivated colitis in mice. Doxycycline displayed immunomodulatory activity in vitro, reducing IL-8 production by intestinal epithelial cells and nitric oxide by macrophages. Doxycycline administration to TNBS-colitic rats (5, 10 and 25 mg/kg) ameliorated the intestinal inflammatory process, being its efficacy comparable to that previously showed by minocycline. Doxycycline treatment was also effective in reducing acute intestinal inflammation in the DSS model of mouse colitis. The association of doxycycline and S. boulardii helped managing colitis in a reactivated model of colitis, by reducing intestinal inflammation and accelerating the recovery and attenuating the relapse. This was evidenced by a reduced disease activity index, colonic tissue damage and expression of inflammatory mediators. This study confirms the intestinal anti-inflammatory activity of doxycycline and supports the potential use of its therapeutic association with S. boulardii for the treatment of inflammatory bowel diseases, in which doxycycline is used to induce remission and long term probiotic administration helps to prevent the relapses.
Assuntos
Antibacterianos/uso terapêutico , Colite/tratamento farmacológico , Doxiciclina/uso terapêutico , Probióticos/uso terapêutico , Saccharomyces , Animais , Células CACO-2 , Colite/induzido quimicamente , Colite/patologia , Terapia Combinada , Citocinas/metabolismo , Sulfato de Dextrana , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Interleucina-8/antagonistas & inibidores , Interleucina-8/biossíntese , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Recidiva , Ácido TrinitrobenzenossulfônicoRESUMO
BACKGROUND: Unprotected intercourse with sex workers is one of the major risk factors for HIV infection. Consistent condom use is a prerequisite to lower the incidence of HIV. METHODS: We assessed the prevalence of condom use and its determinants among company workers engaged with commercial sexual partners in Ecuador. The study was based on a random sample of 115 companies and 1,732 workers stratified by province and working sector and utilized the "Behavioral Surveillance Surveys - Adult questionnaire" developed by Family Health International. RESULTS: Of the 1,561 sexually active workers, 311 (19.9%) reported having intercourse with sex workers. Among them 25.9% did not use a condom at the last sexual intercourse. As for condom use frequency over the last 12 months, 29/208 (13.9%) reported never, 23 (11.1%) sometimes, 24 (11.5%) almost every time and 132 (63.5%) every time. Factors adversely affecting condom use frequency over the last 12 months were female gender (OR = 4.56, 95% CI: 1.45-14.4), older age (OR = 1.07, 95% CI: 1.03-1.10), low educational level (OR = 4.69, 95% CI: 1.95-11.3) and married workers living with spouse (OR = 7.66, 95 % CI: 3.08-19.1). By contrast, factors such as age at first sexual intercourse, job category, HIV transmission and prevention measure knowledge, single workers, previous exposure to HIV intervention programs and having a casual sexual partner were not affecting condom use frequency. When considering condom use during the last sexual intercourse or during the past 12 months with commercial sexual partners, results were similar. CONCLUSIONS: Workers with low education, older age, female gender and those married living with their spouse should be targeted for specific educational interventions.
Assuntos
Preservativos/estatística & dados numéricos , Indústrias , Profissionais do Sexo/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Adulto , Fatores Etários , Estudos Transversais , Equador , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Prevalência , Fatores de Risco , Fatores Sexuais , Fatores SocioeconômicosRESUMO
Nanoparticles of a metal-organic framework (MOF), UiO-66-N3 (Zr6O4OH4(C8H3O4-N3)6), were synthesized. The surface of the MOF was covalently functionalized with oligonucleotides, utilizing a strain promoted click reaction between DNA appended with dibenzylcyclooctyne and azide-functionalized UiO-66-N3 to create the first MOF nanoparticle-nucleic acid conjugates. The structure of the framework was preserved throughout the chemical transformation, and the surface coverage of DNA was quantified. Due to the small pore sizes, the particles are only modified on their surfaces. When dispersed in aqueous NaCl, they exhibit increased stability and enhanced cellular uptake when compared with unfunctionalized MOF particles of comparable size.
Assuntos
DNA/química , Nanopartículas Metálicas/química , Compostos Organometálicos/química , Zircônio/química , Células HeLa , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Tamanho da Partícula , Propriedades de SuperfícieAssuntos
Apoptose/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Dexametasona/farmacologia , Genes p53 , Genótipo , Glutationa Transferase/genética , Humanos , Células Jurkat , Estimativa de Kaplan-Meier , Proteínas de Neoplasias/genética , Medicina de Precisão , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Obesity is associated with intestine dysbiosis and is characterized by a low-grade inflammatory status, which affects vascular function. In the present study, we evaluated the effects of a probiotic with immunomodulatory properties, Lactobacillus coryniformis CECT5711, in obese mice fed on an HFD (high-fat diet). The probiotic treatment was given for 12 weeks, and it did not affect the weight evolution, although it reduced basal glycaemia and insulin resistance. L. coryniformis administration to HFD-induced obese mice induced marked changes in microbiota composition and reduced the metabolic endotoxaemia as it decreased the LPS (lipopolysaccharide) plasma level, which was associated with a significant improvement in gut barrier disruption. Furthermore, it lowered TNFα (tumour necrosis factor α) expression in liver, improving the inflammatory status, and thus the glucose metabolism. Additionally, the probiotic reversed the endothelial dysfunction observed in obese mice when endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings was studied. It also restored the increased vessel superoxide levels observed in obese mice, by reducing NADPH oxidase activity and increasing antioxidant enzymes. Moreover, chronic probiotic administration for 2 weeks also improved endothelial dysfunction and vascular oxidative stress induced by in vivo administration of LPS in control mice fed on a standard chow diet. The results of the present study demonstrate an endothelial-protective effect of L. coryniformis CECT5711 in obese mice by increasing NO bioavailability, suggesting the therapeutic potential of this gut microbiota manipulation to prevent vasculopathy in obesity.
Assuntos
Endotoxemia/prevenção & controle , Inflamação/terapia , Lactobacillus , Obesidade/complicações , Probióticos/uso terapêutico , Animais , Colo/microbiologia , Dieta Hiperlipídica , Endotélio Vascular/fisiopatologia , Endotoxemia/etiologia , Hiperglicemia/terapia , Inflamação/etiologia , Resistência à Insulina/fisiologia , Lipopolissacarídeos/sangue , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Microbiota , Obesidade/microbiologia , Obesidade/fisiopatologia , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Probióticos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Aumento de Peso/fisiologiaRESUMO
Cutaneous apocrine adenocarcinoma (CAA) is a rare adnexal neoplasm that histologically can mimic breast carcinoma metastatic to the skin or apocrine carcinoma arising in ectopic breast tissue. It can present with a wide range of clinical modalities and can often simulate many benign processes, which delays its diagnosis and hinders its prognosis. We describe a case of a 33-year-old man who had a short-evolution small nodule in the right axilla with local lymph node metastases. The immunohistochemical characterization was closer to that of breast adenocarcinoma than to an adnexal neoplasm. This was established as the main differential diagnosis. Diagnosis of cutaneous apocrine adenocarcinoma may be difficult and immunomarkers are not specific. The anatomical criteria and systemic investigation are mandatory to establish the correct diagnosis.