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1.
Toxicol Appl Pharmacol ; 483: 116805, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38191078

RESUMO

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.


Assuntos
Fluoxetina , Lactação , Humanos , Feminino , Criança , Ratos , Animais , Adulto , Fluoxetina/toxicidade , Leite Humano , Antidepressivos/farmacologia , Peso Corporal
2.
Chem Biodivers ; 21(7): e202400680, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38748618

RESUMO

The study aimed to assess the chemical composition of Miconia ibaguensis leaves extracts and fractions obtained from the ethanolic extract (EE), along with evaluating their antifungal, antibacterial, antidiabetic, and antioxidant activities. The ethyl acetate fraction (EAF) exhibited potent antifungal activity against Candida spp (1.95-3.90 µg mL-1) and potent antioxidant activity in the DPPH (1.74±0.07 µg mL-1), FRAP (654.01±42.09 µmol ETrolox/gsample), and ORAC (3698.88±37.28 µmol ETrolox/gsample) methods. The EE displayed inhibition against the α-amylase enzyme (8.42±0.05 µg mL-1). Flavonoids, hydrolysable tannins, triterpenoids, and phenolic acids, identified in the EE and fractions via (-)-HPLC-ESI-MS/MS analysis, were found to contribute to the species' biological activity potentially. These findings suggest promising avenues for further research and potential applications in pharmacology and natural products, offering new possibilities in the fight against global health issues.


Assuntos
Antibacterianos , Antifúngicos , Antioxidantes , Hipoglicemiantes , Melastomataceae , Testes de Sensibilidade Microbiana , Extratos Vegetais , Folhas de Planta , Folhas de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Melastomataceae/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Candida/efeitos dos fármacos , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Cromatografia Líquida de Alta Pressão
3.
BMC Genomics ; 24(1): 91, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36855067

RESUMO

BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.


Assuntos
Óleo de Soja , Transcriptoma , Animais , Masculino , Encéfalo , Cálcio , Dieta/veterinária , Ácidos Graxos , Óleo de Soja/farmacologia , Suínos
4.
Arch Insect Biochem Physiol ; 112(4): e22000, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36656770

RESUMO

Insects have become essential models in studying human metabolic diseases, mainly due to their low maintenance cost and available tools. Both mutations and modified diets induce metabolic states similar to human obesity and diabetes. Here, we explore the effect of a high-calorie, high-fat diet on the metabolism of the beetle Tribolium castaneum. Supplementation of the wheat flour diet with powdered egg yolk for 3 weeks increased the total triacylglycerol and accelerated larval development. In addition, this diet increased the triacylglycerol levels of adult beetles. However, this egg yolk supplementation did not alter the larvae's total glucose levels or lipogenic capacity and ATP citrate lyase activity. The diet also did not change the expression profile of several lipid and carbohydrate metabolism genes and insulin-like peptides. Thus, we conclude that the diet supplemented with egg yolk induces increased fat without causing diabetes phenotypes, as seen in other hypercaloric diets in insects.


Assuntos
Besouros , Tribolium , Humanos , Animais , Tribolium/metabolismo , Gema de Ovo , Pós/metabolismo , Farinha , Triticum , Dieta , Suplementos Nutricionais , Triglicerídeos/metabolismo
5.
Graefes Arch Clin Exp Ophthalmol ; 261(1): 171-184, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35881199

RESUMO

PURPOSE: Our aim was to evaluate the ocular surface in chronic smokers and to assess the benefit of sodium hyaluronate (SH) versus semi-fluorinated alkane (SFA) eyedrops on tear film, meibomian glands, and corneal epithelial thickness (CET). METHODS: This prospective randomized single-blinded study included smokers, who applied one eyedrop of Hyabak® on one eye (SH group) and one eyedrop of EvoTears® on the fellow eye (SFA group) 4 times daily for 2 months, and age-matched non-smokers. Ocular surface parameters, including tear film break-up time (TBUT) test and corneal fluorescein staining (CFS) score, lipid layer thickness (LLT), meibography (LipiView®), and CET measurements (Zeiss Cirrus HD-5000®), were assessed at baseline and after treatment. RESULTS: Seventy-eight eyes were included in the smokers group (39 in the SH subgroup and 39 in the SFA subgroup) and 42 eyes in the control group. At baseline, the smokers group had a higher prevalence of dry eye (100% vs 0%, p < 0.001) and of meibomian gland dysfunction (MGD) and lower CET measurements than controls (p < 0.05). TBUT, CFS, and LLT (controls vs SFA group: 64.02 ± 1.87 nm vs 49.56 ± 4.33 nm, p = 0.05) improved in the SFA subgroup after treatment, but not in the SH subgroup, and became equivalent to those of controls. Prevalence of dry eye decreased in the smokers group after treatment (controls vs SH group vs SFA group: 0% vs 12.82% vs 16.26%, p > 0.05). Meibomian gland morphological parameters and CET did not improve after treatment (p < 0.05). CONCLUSIONS: Smoking is associated with dry eye, MGD, and corneal epithelial thinning that seem to be only partially reversible with topical lubricants, preferably SFA.


Assuntos
Síndromes do Olho Seco , Epitélio Corneano , Disfunção da Glândula Tarsal , Humanos , Glândulas Tarsais , Nicotiana , Estudos Prospectivos , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/etiologia , Lágrimas , Lipídeos
6.
BMC Musculoskelet Disord ; 24(1): 397, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37202816

RESUMO

BACKGROUND: People with patellofemoral pain (PFP) exhibit impaired psychological and pain processing factors (i.e., kinesiophobia, pain catastrophizing and pressure pain thresholds [PPTs]). However, it remains unclear whether these factors have different presentations in women and men with PFP, as well as whether their correlation with clinical outcomes differ according to sex. The aims of this study were to: (1) compare psychological and pain processing factors between women and men with and without patellofemoral pain (PFP); (2) investigate their correlation with clinical outcomes in people with PFP. METHODS: This cross-sectional study included 65 women and 38 men with PFP, 30 women and 30 men without PFP. The psychological and pain processing factors were assessed with the Tampa Scale of Kinesiophobia, Pain Catastrophizing Scale, and PPTs of shoulder and patella measured with an algometer. Clinical outcomes assessed were self-reported pain (Visual Analogue Scale), function (Anterior Knee Pain Scale), physical activity level (Baecke's Questionnaire), and physical performance (Single Leg Hop Test). Generalized linear models (GzLM) and effect sizes [Cohen's d] were calculated for group comparisons and Spearman's correlation coefficients were calculated to investigate correlations between outcomes. RESULTS: Women and men with PFP had higher kinesiophobia (d = .82, p = .001; d = .80, p = .003), pain catastrophizing (d = .84, p < .001; d = 1.27, p < .001), and lower patella PPTs (d = -.85, p = .001; d = -.60, p = .033) than women and men without PFP, respectively. Women with PFP had lower shoulder and patella PPTs than men with PFP (d = -1.24, p < .001; d = -.95, p < .001), but there were no sex differences in those with PFP for psychological factors (p > .05). For women with PFP, kinesiophobia and pain catastrophizing had moderate positive correlations with self-reported pain (rho = .44 and .53, p < .001) and moderate negative correlations with function (rho = -.55 and -.58, p < .001), respectively. For men with PFP, only pain catastrophizing had moderate positive correlations with self-reported pain (rho = .42, p = .009) and moderate negative correlations with function (rho = -.43, p = .007). CONCLUSIONS: Psychological and pain processing factors differ between people with and without PFP and between sexes, respectively. Also, correlations between psychological and pain processing factors with clinical outcomes differ among women and men with PFP. These findings should be considered when assessing and managing people with PFP.


Assuntos
Síndrome da Dor Patelofemoral , Masculino , Humanos , Feminino , Síndrome da Dor Patelofemoral/diagnóstico , Estudos Transversais , Dor , Limiar da Dor , Medição da Dor
7.
BMC Musculoskelet Disord ; 24(1): 372, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170262

RESUMO

BACKGROUND: Patellofemoral pain (PFP) is a common knee disorder that causes persistent pain, lower self-reported function and quality of life. People with PFP also present with altered psychological factors, which are associated with higher levels of pain and dysfunction. Mindfulness-based interventions (MBI) generally consist of meditative practices developed to provide a holistic approach to chronic conditions. However, the effects of MBI on clinical and psychological outcomes for people with PFP remains understudied. METHODS: This assessor-blinded, parallel, two-arm randomized clinical trial aims to investigate the effects of adding an 8-week online MBI program to exercise therapy and patient education on clinical and psychological factors for people with PFP. We also aim to investigate whether psychological factors mediate changes in pain and function. Sixty-two participants with PFP will be recruited and randomized into one of two treatment groups (Mindfulness or Control group). Both groups will receive an 8-week intervention involving exercise therapy and education delivered through an online platform. The Mindfulness group will additionally receive a MBI component including formal and informal practices. Outcomes will be assessed online at baseline, intervention endpoint (follow-up 1) and 12 months after intervention completion (follow-up 2). Comparisons between groups will be performed at all time points with linear mixed models. A mediation analysis will be performed using a 3-variable framework. DISCUSSION: Exercise therapy and patient education are considered the "best management" options for PFP. However, unsatisfactory long-term prognosis remains an issue. It is known that people with PFP present with altered psychological factors, which should be considered during the evaluation and treatment of people with PFP. Adding a MBI to the current best treatment for PFP may improve short and long-term effects by addressing the underlying psychological factors. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR-4yhbqwk, registered in April 6, 2021.


Assuntos
Terapia por Exercício , Atenção Plena , Síndrome da Dor Patelofemoral , Humanos , Terapia por Exercício/métodos , Atenção Plena/métodos , Síndrome da Dor Patelofemoral/diagnóstico , Síndrome da Dor Patelofemoral/terapia , Educação de Pacientes como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Sensors (Basel) ; 23(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37430493

RESUMO

It is crucial to monitor the levels of Non-Ionizing Radiation (NIR) to which the general population may be exposed and compare them to the limits defined in the current standards, in view of the rapid rise of communication services and the prospects of a connected society. A high number of people visits shopping malls and since these locations usually have several indoor antennas close to the public, it is therefore a kind of place that must be evaluated. Thus, this work presents measurements of the electric field in a shopping mall located in Natal, Brazil. We proposed a set of six measurement points, following two criteria: places with great the flow of people and the presence of one or more Distributed Antenna System (DAS), co-sited or not with WiFi access points. Results are presented and discussed in terms of the distance to DAS (conditions: near and far) and flow density of people in the mall (scenarios: low and high number of people). The highest peaks of electric field measured were 1.96 and 3.26 V/m, respectively corresponding to 5% and 8% of the limits defined by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the Brazilian National Telecommunication Agency (ANATEL).


Assuntos
Eletricidade , Telecomunicações , Humanos , Brasil , Radiação não Ionizante
9.
J Pediatr Nurs ; 73: e83-e92, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37596116

RESUMO

OBJECTIVE: To examine the quality of life of children who depend on health technologies as expressed in their own words. METHODS: A parallel and convergent mixed methods design was employed with 30 aged five to 12 year old children who depend on health technologies. Data collection was done through a characterization form, Pediatric Quality of Life Inventory 4.0 questionnaire with the total sample in quantitative phase; semi-structured interviews with a subset of nine participants in qualitative phase. Quantitative and qualitative data were analyzed using descriptive statistics and deductive thematic content analyses, respectively. RESULTS: Findings from PedsQL 4.0 showed that quality of life for children who depend on health technologies is average. However, data integration through mixed methods showed that this average goes beyond quantitative data through hearing the children's own voices. The results from data integration pointed out that children recognize their limitations and adapt to them; what most affects their quality of life is the emotional domain; children reported suffering prejudice due to their physical limitations; and that the school positively impacts their quality of life. CONCLUSIONS: Data integration highlighted that children acknowledge their limitations and pain generated by these devices. Concerns about the future and the ability to do things that other children the same age can do was the most impactful aspect on their quality of life. IMPLICATIONS FOR PRACTICE: Nursing care plans should consider that what affects most children who depend on health technologies' quality of life is anxiety for the future of being incapacitated or dependent.


Assuntos
Tecnologia Biomédica , Enfermagem Pediátrica , Qualidade de Vida , Criança , Pré-Escolar , Humanos
10.
Rev Argent Microbiol ; 55(1): 49-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35803842

RESUMO

Leptospirosis is a neglected zoonosis that is widely distributed in the world. Although it is endemic in Argentina, prevalence remains unknown. The aims of the study were: (i) to determine the prevalence of leptospirosis in humans from a rural community in Tandil Argentina, (ii) to identify infecting Leptospira spp. serogroups, (iii) to identify factors associated with the infection, (iv) to estimate the population attributable fraction (PAF) of the risk factors and (v) to determine the spatial patterns of disease presentation and related risk factors. Blood samples from 202 participants were collected. A survey was conducted to obtain clinical and epidemiological data. Serological testing was performed by the microscopic agglutination test (MAT). Univariate and multivariate methods were applied to evaluate associations. Spatial clusters were investigated for seroprevalence and risk factors. Antibodies were found in 32.2% of participants (95% CI: 25.8-39.1). The most prevalent serogroup was Hebdomadis followed by Sejroe; Icterohaemorrhagiae; Tarassovi and Canicola. Living at lower altitudes (OR: 13.04; 95% CI: 2.60-65.32); not having access to water supply network (OR: 2.95; 95% CI: 1.30-6.69); living close to flooded streets (OR: 2.94; 95% CI: 1.14-7.69) and practicing water sports (OR: 3.12; 95% CI: 1.12-8.33) were associated with seropositivity. Factors related with housing characteristics, services and infrastructure had the higher PAF (from 17% to 81%). A spatial cluster with higher rates of positivity and of the main risk factors was determined. This work contributes useful data for specific preventive measures that should be implemented for the control of the disease.


Assuntos
Leptospira , Leptospirose , Humanos , População Rural , Estudos Soroepidemiológicos , Argentina/epidemiologia , Leptospirose/epidemiologia , Anticorpos Antibacterianos , Fatores de Risco , Análise Espacial
11.
J Vasc Bras ; 22: e20220144, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38162983

RESUMO

Lymphedema is a chronic and progressive disease characterized by fluid accumulation, causing tissue edema as a result of a compromised lymphatic system. Diagnostic ultrasound (DUS) is a method capable of assessing soft tissue characteristics that can be used reliably to diagnose lymphedema as well as for measuring tissue compliance in a clinical setting. This is a systematic review, aiming to evaluate articles that made use of DUS in management of lymphedema secondary to breast cancer. A total of 570 articles were selected, exported to the Rayyan QCRI review program, and then screened by two researchers. From this search, 25 articles were selected after the authors reached consensus and were catalogued as to their main results. Diagnostic ultrasound was identified as an advantageous method that is safe, minimally invasive, low cost, and radiation free and is useful for evaluating the efficacy of therapies used in lymphedema treatment.

12.
Eur J Pediatr ; 181(9): 3511-3521, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35840777

RESUMO

We performed a quality improvement project to necrotizing enterocolitis (NEC) and published our results about the initiative in 2021. However, aspects on the safety of the cooling and how to do therapeutic hypothermia with low technology to preterm infants are not described in this previous reporter. Thus, we aim to describe the steps and management to apply hypothermia in preterm infants using low technology and present the safety aspects regarding the initiative. We performed a quality improvement project to NEC in a reference hospital for neonatology (intensive care unit). Forty-three preterm infants with NEC (modified Bell's stage II/III) were included: 19 in the control group (2015-2018) and 24 in the hypothermic group (2018-2020). The control group received standard treatments. The hypothermia group received standard treatment and underwent passive cooling (35.5 °C, used for 48 h after NEC diagnosis). We reported cooling safety to NEC, assessing hematological and gasometrical parameters, coagulation disorders, clinical instability, and neurological disorders. We described how to perform cooling to preterm infants using incubators' servo-control and the occurrence and management of dysthermia during the cooling. We turn-off the incubator and used the esophageal probe to monitor the temperature every 15 min; if the temperature dropped, the incubator was turned on with a rewarming speed of 0.5 °C/h. The participants' average weights and gestational ages were 1186 g and 32 weeks, respectively. There were no differences among hematological indices, serum parameters (sodium, potassium, creatinine, lactate, and bicarbonate), pH, pCO2, and pO2/FiO2 between the groups during treatment and after rewarming. We did not observe dysthermia, bradycardia, hemodynamic instability, apnea, seizure, bleeding, peri-intraventricular hemorrhage, or any alterations in ventilatory parameters due to the cooling technique in preterm babies. This simple technique was performed without intercurrences through a rigorous team evaluation, with a target cooling speed of 0.5 °C/h. The target temperature was successfully reached between the second and third hours of life with the incubator control in 21 children; ice bags were used in only three cases. The temperature was maintained at the expected level during the programmed cooling period. CONCLUSION: Mild controlled hypothermia for preterm infants with NEC is safe. The cooling of preterm infants could be performed through passive methods, using the servo-control of the incubators for temperature management. WHAT IS KNOWN: • Mild controlled hypothermia to NEC treatment is feasible and associated with a decrease in NEC surgery, short bowel, and death. • Mild controlled hypothermia to preterm is feasible and can be performed through low technology and passive cooling. WHAT IS NEW: • Mild controlled hypothermia to preterm is safe and does not associate with safety adverse effects during and after the cooling. • Preterm infants can be cooled through passive methods by just using the servo control of the incubator, presenting acceptable temperature variance, without dysthermia, achieving and remaining at the target temperature with a proper cooling speed. Mild controlled temperature for preterm infants does not need an additional cooling device.


Assuntos
Enterocolite Necrosante , Hipotermia Induzida , Hipotermia , Criança , Enterocolite Necrosante/terapia , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/métodos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Tecnologia
13.
Caries Res ; 56(5-6): 447-454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36215950

RESUMO

This study evaluated the remineralizing effect of a toothpaste containing surface pre-reacted glass-ionomer (S-PRG) filler on demineralized enamel in situ. For this, 180 bovine enamel samples were demineralized by using a microcosm biofilm model for 3 days. Thereafter, the samples were randomly signed to 15 healthy volunteers and to 3 cross-over in situ phases corresponding to the following treatments: (1) toothpaste containing 1,500 ppm F as NaMFP (positive control, Colgate®Cavity Protection), (2) toothpaste containing 5% S-PRG filler (Shofu®), and (3) placebo toothpaste (negative control prepared by Shofu®). Four demineralized enamel blocks were fixed into each palatal appliance per phase. The volunteers wore the appliances for 5 days and were trained to brush their teeth 2 times for 2 min a day, while one drop of the toothpaste's slurry (1:3) was dripped on each sample for the same period. The surface hardness and TMR analyses were done and analyzed by ANOVA/Tukey and t test (p < 0.05). S-PRG filler and Colgate® toothpastes were equally able to improve 2-2.5× enamel remineralization by the analysis of % surface hardness recovery. However, S-PRG toothpaste was the only one able to significantly improve ΔΔZ (the integrated mineral loss recovery: 1,489 ± 503 %vol.µm) compared to placebo (1,050 ± 467 %vol.µm), while Colgate® did not differ from placebo. No differences were seen between the groups with respect to ΔLD. S-PRG filler and Colgate® toothpastes show similar potential to remineralize the lesion surface. However, S-PRG toothpaste is better to recover mineral loss at the subsurface area.


Assuntos
Fluoretos , Cremes Dentais , Animais , Bovinos , Humanos , Esmalte Dentário/patologia , Fluoretos/farmacologia , Minerais , Fluoreto de Sódio/farmacologia , Remineralização Dentária/métodos , Cremes Dentais/farmacologia , Cremes Dentais/uso terapêutico
14.
Curr Genet ; 67(4): 663-672, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33751147

RESUMO

The CRISPR-Cas are adaptive immune systems found in archaea and bacteria, responsible for providing sequence-specific resistance against foreign DNA. Strains of Pseudomonas aeruginosa may carry CRISPR/Cas system types I-F, I-E and/or I-C; however, several aspects related to the epidemiology and functionality of these systems have not yet been revealed. Here, we report 13 genomes of clinical strains of P. aeruginosa from Brazil that were positive for CRISPR/Cas system types I-F and I-E, a rare feature in this species. The phylogenetic tree, which was constructed with 161 other publicly available genomes, suggested no direct relationship between positive strains, and the various types of CRISPR/Cas systems were spread throughout the tree. Comparative analysis of the genetic locations of type I-F and a specific orphan CRISPR array (without cas genes), named the LES locus, showed sequence similarities between this orphan locus and type I-F, but these LES loci were inserted in a different genomic location. We also report the presence of prophages, the presence of anti-CRISPR genes, and possibly the presence of self-targeting spacers. Here, we conclude that CRISPR/Cas is highly associated with certain lineages and is spread throughout the phylogenetic tree, showing no clear pattern of evolutionary distribution. Moreover, the LES locus might be a CRISPR1 locus related to type I-F that may have been misplaced and maintained over time. Furthermore, strains carrying I-F and I-E are rare, and not all of them are closely related. Further functional work is needed to better comprehend if aspects reported in this study are functional, including the LES locus, self-targeting spacers, anti-CRISPR protection, and I-F/I-E-carrying lineages.


Assuntos
Sistemas CRISPR-Cas/genética , Genoma Bacteriano/genética , Genômica , Pseudomonas aeruginosa/genética , Bactérias/genética , Brasil , Humanos , Filogenia , Pseudomonas aeruginosa/patogenicidade
15.
Pharmacol Res ; 173: 105911, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34560251

RESUMO

In melanomas, therapy resistance can arise due to a combination of genetic, epigenetic and phenotypic mechanisms. Due to its crucial role in DNA supercoil relaxation, TOP1 is often considered an essential chemotherapeutic target in cancer. However, how TOP1 expression and activity might differ in therapy sensitive versus resistant cell types is unknown. Here we show that TOP1 expression is increased in metastatic melanoma and correlates with an invasive gene expression signature. More specifically, TOP1 expression is highest in cells with the lowest expression of MITF, a key regulator of melanoma biology. Notably, TOP1 and DNA Single-Strand Break Repair genes are downregulated in BRAFi- and BRAFi/MEKi-resistant cells and TOP1 inhibition decreases invasion markers only in BRAFi/MEKi-resistant cells. Thus, we show three different phenotypes related to TOP1 levels: i) non-malignant cells with low TOP1 levels; ii) metastatic cells with high TOP1 levels and high invasiveness; and iii) BRAFi- and BRAFi/MEKi-resistant cells with low TOP1 levels and high invasiveness. Together, these results highlight the potential role of TOP1 in melanoma progression and resistance.


Assuntos
DNA Topoisomerases Tipo I , Resistencia a Medicamentos Antineoplásicos , Melanoma , Neoplasias Cutâneas , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/metabolismo , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Melanoma/mortalidade , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade
16.
Bioorg Med Chem Lett ; 50: 128334, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34425202

RESUMO

Compounds capable of inhibiting the efflux pump mechanism are a promising alternative against bacterial resistance because, when combined with antibiotics, they can increase the effectiveness of these drugs by inhibiting active efflux. Elaiophylin, derived from Streptomyces hygroscopicus, is a natural antibiotic that exhibits a variety of biological activities, including antibacterial activity. However, its potential as an inhibitor of the bacterial efflux mechanism has not been investigated. This study evaluated the ability of Elaiophylin to inhibit the NorA efflux pump in Staphylococcus aureus strains. Therefore, tests were performed to obtain the Minimum Inhibitory Concentration (MIC) and to verify the ability of Elaiophylin to potentiate the MIC of the antibiotic Norfloxacin and Ethidium Bromide (EtBr), known substrates of NorA efflux. Real-time PCR and molecular docking assays were also performed to assess the potential of Elaiophylin against NorA. The strains SA-1199 (wild type) and SA-1199B (NorA over-expressed) of S. aureus were used for this study. The results showed that Elaiophylin significantly decreased the MIC of Norfloxacin and EtBr, increasing the activity of these substrates against S. aureus, which carries the efflux protein NorA. However, Elaiophylin provided a non-significant reduction in norA gene expression, however, molecular docking demonstrated a high binding affinity between Elaiophylin and NorA efflux protein, indicating that Elaiophylin can act as a potential NorA in S. aureus.


Assuntos
Proteínas de Bactérias/metabolismo , Macrolídeos/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Streptomyces/química , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Sítios de Ligação , Farmacorresistência Bacteriana Múltipla , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Macrolídeos/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Conformação Proteica , Relação Estrutura-Atividade
17.
J Hum Nutr Diet ; 34(4): 670-678, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33811690

RESUMO

BACKGROUND: The social isolation enforced as a result of the new coronavirus (COVID-19) pandemic may impact families' lifestyle and eating habits. The present study aimed to assess the behaviour and dietary patterns of Brazilian children and adolescents during the social isolation imposed by the COVID-19 pandemic. METHODS: The present study was conducted using an online, anonymous cross-sectional survey with 589 children and 720 adolescents from Brazil during a nationwide social isolation policy. The Mann-Whitney U-test or the Kruskal-Wallis with the Dunn post-hoc method and a radar chart were used to compare the weekly consumption of each food by age group and isolation status. p < 0.05 was considered statistically significant. Analyses were conducted using R statistical software, version 4.0.2 (R Foundation for Statisitical Computing). RESULTS: We found that isolated families showed breakfast eating habits and the consumption of raw salad, vegetables, beans and soft drinks. Lower-class isolated families and those from the Northeast region consumed fruits, juices, vegetables and beans less frequently. Compared to children, adolescents were less isolated (p = 0.016), less active (p < 0.001), exposed to longer screen time (p < 0.001), showed an inadequate sleeping pattern (p = 0.002) and were from lower-class families (p < 0.001). CONCLUSIONS: Social isolation affected the eating habits of children and adolescents. Non-isolated families presented a lower consumption of healthy food, especially those among the lower class, from Northeast Brazil, as well as adolescents.


Assuntos
COVID-19/prevenção & controle , Dieta/estatística & dados numéricos , Comportamento Alimentar/psicologia , Quarentena/psicologia , Isolamento Social/psicologia , Adolescente , Brasil , Criança , Estudos Transversais , Dieta/psicologia , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , SARS-CoV-2
18.
Chem Biodivers ; 18(8): e2100307, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34086414

RESUMO

Brazilian green and red propolis stand out as commercial products for different medical applications. In this article, we report the antimicrobial activities of the hydroalcoholic extracts of green (EGP) and red (ERP) propolis, as well as guttiferone E plus xanthochymol (8) and oblongifolin B (9) from red propolis, against multidrug-resistant bacteria (MDRB). We undertook the minimal inhibitory (MIC) and bactericidal (MBC) concentrations, inhibition of biofilm formation (MICB50 ), catalase, coagulase, DNase, lipase, and hemolysin assays, along with molecular docking simulations. ERP was more effective by displaying MIC and MBC values <100 µg mL-1 . Compounds 8 and 9 displayed the lowest MIC values (0.98 to 31.25 µg mL-1 ) against all tested Gram-positive MDRB. They also inhibited the biofilm formation of S. aureus (ATCC 43300 and clinical isolate) and S. epidermidis (ATCC 14990 and clinical isolate), with MICB50 values between 1.56 and 6.25 µg mL-1 . The molecular docking results indicated that 8 and 9 might interact with the catalase's amino acids. Compounds 8 and 9 have great antimicrobial potential.


Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Própole/química , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Benzofenonas/química , Benzofenonas/isolamento & purificação , Benzofenonas/metabolismo , Benzofenonas/farmacologia , Sítios de Ligação , Biofilmes/efeitos dos fármacos , Brasil , Catalase/química , Catalase/metabolismo , Domínio Catalítico , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Própole/metabolismo , Própole/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
19.
Eur J Immunol ; 49(7): 1038-1051, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30939218

RESUMO

Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution phase of inflammation is unknown. Here, we investigated the effects of inhibition of S1P receptors and the blockade of S1P synthesis in BALB/c mice and human neutrophils. S1P and S1PR1-3 receptors expression were increased in cells from the pleural cavity stimulated with LPS. Using different antagonists of S1PRs and inhibitors of different steps of the metabolic pathway of S1P production, we show that S1P and its receptors are involved in regulating neutrophil survival and resolution of inflammation in the pleural cavity. Given the role of the S1P-S1PR axis in resolution of inflammation, we sought to identify whether blockade at different levels of the sphingosine-1-phosphate synthesis pathway could affect neutrophil survival in vitro. Inhibitors of the S1P pathway were also able to induce human neutrophil apoptosis. In addition, blockade of S1P synthesis or its receptor facilitated the efferocytosis of apoptotic neutrophil. Taken together, our data demonstrate a fundamental role for S1P in regulating the outcome of inflammatory responses, and position S1P-S1PR axis as a potential target for treatment of neutrophilic inflammation.


Assuntos
Inflamação/imunologia , Lisofosfolipídeos/metabolismo , Neutrófilos/imunologia , Cavidade Pleural/imunologia , Receptores de Esfingosina-1-Fosfato/metabolismo , Esfingosina/análogos & derivados , Animais , Apoptose , Sobrevivência Celular , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ativação de Neutrófilo , Transdução de Sinais , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores
20.
J Toxicol Environ Health A ; 83(23-24): 730-747, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-32998665

RESUMO

POINCIANELLA BRACTEOSA: has been widely used in folk medicine to treat catarrhal infections, diarrhea, and anemia; however, phytochemical and toxicogenetic data are still lacking. The objective of this study was to examine the phytochemical and antioxidant characteristics as well as assess cytogenotoxicity and antigenotoxicity in hexane (HF), ether (EF) and ethyl acetate (AF) fractions of P. bracteosa leaves using Allium cepa bioassay. Phytochemical analysis revealed the presence of saponins and phenolic groups. EF fraction contained a higher content of total phenolics (441.23 ± 1.82 mg GAE/g), while HF fraction showed a higher content of total flavonoids (84.77 ± 5.33 mg QE/g). Higher antioxidant activity was observed in EF (EC50 25.06 ± 0.07 µg/ml). Cytotoxic effect was verified for all fractions, but no chromosomal alterations were observed in the A. cepa assay. With respect to antigenotoxicity, the protective effect of EF and AF fractions was attributed to as evidenced by the modulation of mutagenic action of methyl methanesulfonate (MMS), mainly by inhibiting the development of micronuclei. Among the fractions, EF was considered the most promising, as it exhibited higher antioxidant activity, was not genotoxic, exerted protective activity against the damage induced by MMS and also presented cytotoxic activity, a desired quality in the search for natural anticarcinogenic compounds.


Assuntos
Antioxidantes/farmacologia , Fabaceae/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes/química , Flavonoides/análise , Testes de Mutagenicidade , Fenóis/análise , Compostos Fitoquímicos/química , Extratos Vegetais/química , Folhas de Planta/química
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