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1.
Nano Lett ; 24(12): 3557-3565, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38499397

RESUMO

Magnetic skyrmions are topological spin textures which are envisioned as nanometer scale information carriers in magnetic memory and logic devices. The recent demonstrations of room temperature skyrmions and their current induced manipulation in ultrathin films were first steps toward the realization of such devices. However, important challenges remain regarding the electrical detection and the low-power nucleation of skyrmions, which are required for the read and write operations. Here, we demonstrate, using operando magnetic microscopy experiments, the electrical detection of a single magnetic skyrmion in a magnetic tunnel junction (MTJ) and its nucleation and annihilation by gate voltage via voltage control of magnetic anisotropy. The nucleated skyrmion can be manipulated by both gate voltages and external magnetic fields, leading to tunable intermediate resistance states. Our results unambiguously demonstrate the readout and voltage controlled write operations in a single MTJ device, which is a major milestone for low power skyrmion based technologies.

2.
Am J Physiol Heart Circ Physiol ; 326(3): H497-H510, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38063810

RESUMO

Cardiovascular and metabolic diseases such as hypertension, type 2 diabetes, and obesity develop long-term fibrotic processes in the heart, promoting pathological cardiac remodeling, including after myocardial infarction, reparative fibrotic processes also occur. These processes are regulated by many intracellular signaling pathways that have not yet been completely elucidated, including those associated with microRNA (miRNA) expression. miRNAs are small RNA transcripts (18-25 nucleotides in length) that act as posttranscriptionally regulators of gene expression, inhibiting or degrading one or more target messenger RNAs (mRNAs), and proven to be involved in many biological processes such as cell cycle, differentiation, proliferation, migration, and apoptosis, directly affecting the pathophysiology of several diseases, including cardiac fibrosis. Exercise training can modulate the expression of miRNAs and it is known to be beneficial in various cardiovascular diseases, attenuating cardiac fibrosis processes. However, the signaling pathways modulated by the exercise associated with miRNAs in cardiac fibrosis were not fully understood. Thus, this review aims to analyze the expression of miRNAs that modulate signaling pathways in cardiac fibrosis processes that can be regulated by exercise training.


Assuntos
Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Exercício Físico , Transdução de Sinais , RNA Mensageiro/genética , Fibrose
3.
Exp Brain Res ; 242(8): 1871-1879, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38864869

RESUMO

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO2max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.


Assuntos
Envelhecimento , Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Depressão , Treinamento Intervalado de Alta Intensidade , Hipocampo , Ratos Wistar , Animais , Hipocampo/metabolismo , Ratos , Depressão/metabolismo , Depressão/terapia , Depressão/fisiopatologia , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Ansiedade/metabolismo , Ansiedade/terapia , Ansiedade/fisiopatologia , Treinamento Intervalado de Alta Intensidade/métodos , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Aprendizagem em Labirinto/fisiologia , Condicionamento Físico Animal/fisiologia , Memória Espacial/fisiologia
4.
Nano Lett ; 23(17): 7869-7875, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37589447

RESUMO

Spintronic devices have recently attracted a lot of attention in the field of unconventional computing due to their non-volatility for short- and long-term memory, nonlinear fast response, and relatively small footprint. Here we demonstrate experimentally how voltage driven magnetization dynamics of dual free layer perpendicular magnetic tunnel junctions can emulate spiking neurons in hardware. The output spiking rate was controlled by varying the dc bias voltage across the device. The field-free operation of this two-terminal device and its robustness against an externally applied magnetic field make it a suitable candidate to mimic the neuron response in a dense neural network. The small energy consumption of the device (4-16 pJ/spike) and its scalability are important benefits for embedded applications. This compact perpendicular magnetic tunnel junction structure could finally bring spiking neural networks to sub-100 nm size elements.

5.
Environ Monit Assess ; 196(6): 534, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727864

RESUMO

Escherichia coli is one of the key bacteria responsible for a variety of diseases in humans and livestock-associated infections around the globe. It is the leading cause of mortality in neonatal and weaned piglets in pig husbandry, causing diarrhea and significant harm to the industry. Furthermore, the frequent and intensive use of antimicrobials for the prevention of diseases, particularly gastrointestinal diseases, may promote the selection of multidrug-resistant (MDR) strains. These resistant genotypes can be transmitted through the excrement of animals, including swine. It is common practice to use porcine manure processed by biodigesters as fertilizer. This study aimed to examine the antimicrobial susceptibility, the presence of virulence genes frequently associated with pathotypes of intestinal pathogenic E. coli (InPEC), and antimicrobial resistance genes (ARGs) of 28 E. coli isolates collected from swine manure fertilizers. In addition, the enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) technique was used to investigate the genetic relationship among the strains. Using disk diffusion, the antimicrobial susceptibility profiles of the strains were determined. Using polymerase chain reaction (PCR), 14 distinct virulence genes associated with the most prevalent diarrhea and intestinal pathogenic E. coli (DEC/InPEC) and five ARGs were analyzed. All isolates tested positive for multidrug resistance. There was no detection of any of the 14 virulence genes associated with InPECs, indicating the presence of an avirulent commensal microbiota. Molecular classification by ERIC-PCR revealed that the majority of isolates (27 isolates) coalesced into a larger cluster with a genetic similarity of 47.7%; only one strain did not cluster in this cluster, indicating a high level of genetic diversity among the analyzed isolates. Thus, it is of the utmost importance to conduct epidemiological surveillance of animal breeding facilities in order to determine their microbiota and formulate plans to reduce the use of antimicrobials and improve animal welfare.


Assuntos
Farmacorresistência Bacteriana Múltipla , Escherichia coli , Fertilizantes , Esterco , Animais , Suínos , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Esterco/microbiologia , Brasil , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia
6.
J Arthroplasty ; 38(12): 2731-2738.e3, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37321521

RESUMO

BACKGROUND: Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic accuracy and (ii) to evaluate their performance according to different PJI definitions. METHODS: A systematic review and meta-analysis was performed using studies that reported diagnostic accuracy of synovial fluid biomarkers using validated PJI definitions published from 2010 to March 2022. A database search was performed through PubMed, Ovid MEDLINE, Central, and Embase. The search identified 43 different biomarkers with four being the more commonly studied, with 75 papers overall: alpha-defensin; leukocyte esterase; synovial fluid C-reactive protein; and calprotectin. RESULTS: Overall accuracy was higher for calprotectin, followed by alpha-defensin, leukocyte esterase, and synovial fluid C-reactive protein with sensitivities of 78 to 92% and specificities of 90 to 95%. Their diagnostic performance was different according to which definition was adopted as the reference. Specificity was consistently high across definitions for all four biomarkers. Sensitivity varied the most with lower values for the more sensitive European Bone and Joint Infection Society or Infectious Diseases Society of America definitions with higher values for the Musculoskeletal Infection Society definition. The International Consensus Meeting 2018 definition showed intermediate values. CONCLUSION: All evaluated biomarkers had good specificity and sensitivity, making their use acceptable in the diagnosis of PJI. Biomarkers perform differently according to the selected PJI definitions.


Assuntos
Artrite Infecciosa , Infecções Relacionadas à Prótese , alfa-Defensinas , Humanos , Proteína C-Reativa/análise , Sensibilidade e Especificidade , Líquido Sinovial/química , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/metabolismo , Biomarcadores/metabolismo , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/metabolismo , Complexo Antígeno L1 Leucocitário
7.
Nano Lett ; 22(10): 4000-4005, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35576455

RESUMO

Perpendicular shape anisotropy (PSA) offers a practical solution to downscale spin-transfer torque magnetoresistive random-access memory (STT-MRAM) beyond the sub-20 nm technology node while retaining thermal stability. However, our understanding of the thermomagnetic behavior of PSA-STT-MRAM is often indirect, relying on magnetoresistance measurements and micromagnetic modeling. Here, the magnetism of a NiFe PSA-STT-MRAM nanopillar is investigated using off-axis electron holography, providing spatially resolved magnetic information as a function of temperature. Magnetic induction maps reveal the micromagnetic configuration of the NiFe storage layer (∼60 nm high, ≤20 nm diameter), confirming the PSA induced by its 3:1 aspect ratio. In situ heating demonstrates that the PSA of the storage layer is maintained up to at least 250 °C, and direct quantitative measurements reveal a moderate decrease of magnetic induction. Hence, this study shows explicitly that PSA provides significant stability in STT-MRAM applications that require reliable performance over a range of operating temperatures.

8.
Acta Orthop ; 94: 8-18, 2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36701120

RESUMO

BACKGROUND AND PURPOSE: A new periprosthetic joint infection (PJI) definition has recently been proposed by the European Bone and Joint Infection Society (EBJIS). The goals of this paper are to evaluate its diagnostic accuracy and compare it with previous definitions and to assess its accuracy in preoperative diagnosis. PATIENTS AND METHODS: We retrospectively evaluated a multicenter cohort of consecutive revision total hip and knee arthroplasties. Cases with minimum required diagnostic workup were classified according to EBJIS, 2018 International Consensus Meeting (ICM 2018), Infectious Diseases Society of America (IDSA), and modified 2013 Musculoskeletal Infection Society (MSIS) definitions. 2 years' minimum follow-up was required to assess clinical outcome. RESULTS: Of the 472 cases included, PJI was diagnosed in 195 (41%) cases using EBJIS; 188 (40%) cases using IDSA; 172 (36%) using ICM 2018; and 145 (31%) cases using MSIS. EBJIS defined fewer cases as intermediate (5% vs. 9%; p = 0.01) compared with ICM 2018. Specificity was determined by comparing risk of subsequent PJI after revision surgery. Infected cases were associated with higher risk of subsequent PJI in every definition. Cases classified as likely/confirmed infections using EBJIS among those classified as not infected in other definitions showed a significantly higher risk of subsequent PJI compared with concordant non-infected cases using MSIS (RR = 3, 95% CI 1-6), but not using ICM 2018 (RR = 2, CI 1-6) or IDSA (RR = 2, CI 1-5). EBJIS showed the highest agreement between pre-operative and definitive classification (k = 0.9, CI 0.8-0.9) and was better at ruling out PJI with an infection unlikely result (sensitivity 89% [84-93], negative predictive value 90% [85-93]). CONCLUSION: The newly proposed EBJIS definition emerged as the most sensitive of all major definitions. Cases classified as PJI according to the EBJIS criteria and not by other definitions seem to have increased risk of subsequent PJI compared with concordant non-infected cases. EBJIS classification is accurate in ruling out infection preoperatively.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Humanos , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Infecções Relacionadas à Prótese/cirurgia , Artroplastia do Joelho/efeitos adversos , Valor Preditivo dos Testes , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/etiologia , Artrite Infecciosa/cirurgia , Reoperação/efeitos adversos , Sensibilidade e Especificidade , Líquido Sinovial , Biomarcadores
9.
Rev Cardiovasc Med ; 23(1): 29, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35092221

RESUMO

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, and its prevalence has grown worldwide. Several pathophysiological processes contribute to the development, progression and aggravating of the disease, for example, decreased insulin synthesis and secretion, insulin resistance, inflammation, and apoptosis, all these processes are regulated by various epigenetic factors, including microRNAs (miRNAs). MiRNAs are small non-coding RNAs, which are around 20 nucleotides in length and are regulators of gene expression at the post-transcriptional level, have a specific function of inhibiting or degrading a messenger RNA target. Thus, miRNAs modulate the expression of many associated genes with the pathophysiological processes in T2DM. On the other hand, miRNAs are also modulated through physical exercise (PE), which induces a change in their expression pattern during and after exercise. Some scientific evidence shows that PE modulates miRNAs beneficially and improves the signaling pathway of insulin resistance, however, little is known about the function of PE modulating miRNAs associated with the processes of insulin secretion, inflammation, and apoptosis. Thus, the objective of this review is to identify the miRNAs expression pattern in T2DM and compare it with the exercise-induced miRNAs expression pattern, identifying the signaling pathways that these miRNAs are regulating in the processes of insulin secretion, insulin resistance, inflammation, and apoptosis in T2DM, and how PE may have a potential role in modulating these signal transduction pathways, promoting benefits for patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Exercício Físico , Resistência à Insulina , MicroRNAs , Transdução de Sinais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Humanos , Resistência à Insulina/genética , MicroRNAs/genética
10.
Phys Rev Lett ; 128(7): 077401, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35244431

RESUMO

We report on the experimental evidence of magnetic helicoidal dichroism, observed in the interaction of an extreme ultraviolet vortex beam carrying orbital angular momentum with a magnetic vortex. Numerical simulations based on classical electromagnetic theory show that this dichroism is based on the interference of light modes with different orbital angular momenta, which are populated after the interaction between light and the magnetic topology. This observation gives insight into the interplay between orbital angular momentum and magnetism and sets the framework for the development of new analytical tools to investigate ultrafast magnetization dynamics.

11.
Mol Biol Rep ; 49(6): 4965-4975, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35092564

RESUMO

BACKGROUND: Depression is a global disease that affects the physical and mental health of people of all ages. Non-pharmacological and unconventional methods of treatment, such as regular physical exercise, have been recommended to treat depression. METHODS: Here, we briefly review the literature about the physiological and molecular mechanisms of exercise antidepressants in depressive-like behavior in animal models of depression. RESULTS: The main hysiological and molecular mechanisms of physical exercise in depression include blood flow changes in several areas of the brain, increase in brain serotonin synthesis, increase in antioxidant enzymes, increase in serum and brain brain-derived neuro factor (BDNF) levels, decrease in cortisol levels and reduced inflammation in peripheral and brain tissues. Physical exercise also leads to increased activation of the phosphatidylinositol-3-kinase (PI3K), PGC-1α/FNDC5/Irisin pathway, BDNF concentrations (serum and cerebral), extracellular signal-regulated kinase and cAMP-response element binding protein (mainly in neurons of the hippocampus and prefrontal cortex), which together contribute to fight or inhibit the development of depression symptoms. These molecular and physiological mechanisms work in synchrony, further enhancing their effects. CONCLUSION: Physical exercise can be used as a safe and effective non-pharmacological treatment in depression.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Condicionamento Físico Animal , Animais , Antioxidantes , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/terapia , Modelos Animais de Doenças , Exercício Físico , Fibronectinas/metabolismo , Hipocampo/metabolismo , Humanos , Hidrocortisona , Modelos Animais , Serotonina
12.
Metab Brain Dis ; 37(4): 851-857, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35286534

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to cognitive decline and memory loss. Insulin resistance in central nervous system (CNS) is a common feature in dementia. Defective insulin signaling is associated to higher levels of inflammation and to neuronal dysfunction. A reactive gliosis, a change that occurs in glial cells due to damage in CNS, seems to be one of the most important pro-inflammatory mechanisms in AD pathology. The first response to CNS injury is the migration of macrophages and microglia to the specific site of the injury. Oligodendrocytes are also recruited to to contribute with remyelination. The last component of a reactive gliosis is astrogliosis, which is the enhancement of astrocytes expression with concomitant changes in its morphology being the main cells of the glial scar. Here, we review the mechanisms by which a reactive gliosis can induce or contribute to the development and progression of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/patologia , Amnésia , Gliose/patologia , Humanos , Inflamação/patologia , Transtornos da Memória/etiologia
13.
Metab Brain Dis ; 37(3): 559-580, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35075500

RESUMO

Alzheimer's disease (AD) is the most common type of dementia. The evolution and aggregation of amyloid beta (ß) oligomers is linked to insulin resistance in AD, which is also the major characteristic of type 2 diabetes (T2D). Being physically inactive can contribute to the development of AD and/or T2D. Aerobic exercise training (AET), a type of physical exercise, can be useful in preventing or treating the negative outcomes of AD and T2D. AD, T2D and AET can regulate the expression of microRNAs (miRNAs). Here, we review some of the changes in miRNAs expression regulated by AET, AD and T2D. MiRNAs play an important role in the gene regulation of key signaling pathways in both pathologies, AD and T2D. MiRNA dysregulation is evident in AD and has been associated with several neuropathological alterations, such as the development of a reactive gliosis. Expression of miRNAs are associated with many pathophysiological mechanisms involved in T2D like insulin synthesis, insulin resistance, glucose intolerance, hyperglycemia, intracellular signaling, and lipid profile. AET regulates miRNAs levels. We identified 5 miRNAs (miR-21, miR-29a/b, miR-103, miR-107, and miR-195) that regulate gene expression and are modulated by AET on AD and T2D. The identified miRNAs are potential targets to treat the symptoms of AD and T2D. Thus, AET is a non-pharmacological tool that can be used to prevent and fight the negative outcomes in AD and T2D.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , MicroRNAs , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Exercício Físico , Humanos , MicroRNAs/metabolismo
14.
Metab Brain Dis ; 37(2): 463-471, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34762211

RESUMO

The prevalence of overweight and obesity is increasing worldwide, which has been associated with poor cognitive outcomes. Participating in regular physical exercise may also improve cognition, and levels of brain-derived neurotrophic factor (BDNF), but the optimal exercise prescription remains to be elucidated. The purpose of the present study is to compare the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on cognition, and serum BDNF levels in middle-aged and overweight men. Twenty-five sedentary, overweight men participated in the 8-week training intervention. Subjects were randomized into MICT (n = 12) or HIIT (n = 13) and performed exercise sessions 3x/week for 8-weeks. Cognitive function, and serum BDNF levels were assessed pre- and post-intervention. Statistical analysis was carried out using the Graph Pad Prism 7.0, and the level of significance was set at 5%. Significant improvements were observed in cognitive test scores, and BDNF levels in MICT and HIIT groups (p < 0.05). There were no significant differences in cognitive function between MICT and HIIT. The present study implicates that 8 weeks of MICT or HIIT may be a very useful non-pharmacological treatment option to improve cognitive function, and BDNF levels in middle-aged overweight men.


Assuntos
Treinamento Intervalado de Alta Intensidade , Fator Neurotrófico Derivado do Encéfalo , Cognição , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/terapia , Sobrepeso/terapia
15.
Int J Neurosci ; 132(11): 1091-1101, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33287589

RESUMO

PURPOSE/AIM: Zika virus (ZIKV) infection during the pregnancy period is related to microcephaly and neurobehavioral disorders at birth, while prenatal exercise is supposed to provide neuroprotection in newborns pups. The aim of this study was to investigate the neurological consequences of exercise during prenatal ZIKV exposure to mice pups. MATERIAL AND METHODS: Twelve weeks female mice were randomly assigned into three groups: Control group, intraperitoneally injected with saline (Control); untrained group, intraperitoneally injected with ZIKV (ZIKV); and trained group, intraperitoneally injected with ZIKV (ZIKV/swim). There was one familiarization week prior to the beginning of the swimming training. Dams swam for 60 min/session, 5 days/week, during 4 weeks. Mating occurred between the fifth and seventh day of the first week of the swimming training. ZIKV 106 plaque-forming units/100 µl (106 PFUs/100 µl) or an equal volume of saline was intraperitoneally injected in the pregnant mice at embryonic day 10.5. Pup's body mass and brain weight were measured at postnatal day 1 (P1). Behavioral tests were performed from P30 to P35. Thereafter, hippocampal levels of syntaxin-1, GFAP, IBA-1, and BDNF were measured. RESULTS: Exercise during prenatal ZIKV exposure prevented brain atrophy, development of depression, anxiety, and disruption of social behavior. Exercise during prenatal ZIKV exposure inhibited the overexpression of microglia (IBA-1) and astrocytes (GFAP), with reduction of BDNF levels in the hippocampi of female and male mice pups. No significant changes were seen in syntaxin-1 levels. CONCLUSION: Our findings reveal beneficial effects of exercise during pregnancy exposure to ZIKV in mice pups.


Assuntos
Infecção por Zika virus , Zika virus , Gravidez , Animais , Camundongos , Masculino , Feminino , Fator Neurotrófico Derivado do Encéfalo , Microglia , Proteínas Qa-SNARE
16.
Int J Mol Sci ; 23(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35682659

RESUMO

Cutaneous melanoma emerges from the malignant transformation of melanocytes and is the most aggressive type of skin cancer. The progression can occur in different stages: radial growth phase (RGP), vertical growth phase (VGP), and metastasis. Reactive oxygen species contribute to all phases of melanomagenesis through the modulation of oncogenic signaling pathways. Tetrahydrobiopterin (BH4) is an important cofactor for NOS coupling, and an uncoupled enzyme is a source of superoxide anion (O2•-) rather than nitric oxide (NO), altering the redox homeostasis and contributing to melanoma progression. In the present work, we showed that the BH4 amount varies between different cell lines corresponding to distinct stages of melanoma progression; however, they all presented higher O2•- levels and lower NO levels compared to melanocytes. Our results showed increased NOS expression in melanoma cells, contributing to NOS uncoupling. BH4 supplementation of RGP cells, and the DAHP treatment of metastatic melanoma cells reduced cell growth. Finally, Western blot analysis indicated that both treatments act on the PI3K/AKT and MAPK pathways of these melanoma cells in different ways. Disruption of cellular redox homeostasis by the altered BH4 concentration can be explored as a therapeutic strategy according to the stage of melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Homeostase , Humanos , Melanoma/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Oxirredução , Fosfatidilinositol 3-Quinases/metabolismo
17.
J Sci Food Agric ; 102(4): 1391-1396, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34370875

RESUMO

BACKGROUND: Round fish is one of the most consumed fish in Brazil. Farmed fish feed is based mainly on grains, which are susceptible to contamination by mold and mycotoxins. Aspergillus spp., Penicillium spp. and Fusarium spp. are the major mycotoxins producers. The presence of potentially toxigenic fungi in the diet is a concern due to the possibility of cumulative toxins in fish tissues, becoming a risk to food safety. This study aims to assess the mycobiota of fish feed and the occurrence of aflatoxin residues in round fish tissues. Feed and fish samples were collected from fish farming and fish pay properties. Feed was submitted to mold counting and mold identification. The round fish liver and muscle were submitted to the detection and quantification of aflatoxins B1 , B2 , G1 and G2 by high-performance liquid chromatography. RESULTS: In evaluated feed, mold counts in the samples ranged from 2.0 to 4.7 log colony forming units g-1 and the major genera found were Penicillium (61.5%) and Aspergillus (34.6). Aflatoxin B1 (AFB1 ) was detected in 70% liver samples and 43.3% muscle samples, at levels up to 5.70 and 1.13 µg kg-1 , respectively. CONCLUSION: It is concluded that, although the levels were lower than those recommended by Brazilian legislation, round fish are being exposed to diets naturally contaminated by aflatoxins and are susceptible to toxins accumulation in tissues. Therefore, regulations regarding feed should consider limits for mold and aflatoxin contamination in fish edible tissues should be monitored in order to ensure consumers' safety. © 2021 Society of Chemical Industry.


Assuntos
Aflatoxinas , Micotoxinas , Aflatoxina B1/análise , Aflatoxinas/análise , Ração Animal/análise , Animais , Contaminação de Alimentos/análise , Micotoxinas/análise
18.
Environ Monit Assess ; 195(1): 204, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36527506

RESUMO

Antimicrobial resistance is one of the severe threats to global health. Hospital sewage can serve as a reservoir for multi-resistant bacteria and promote the spread of antimicrobial resistance. This study aimed to investigate the antimicrobial susceptibility and the pathogenic potential of Enterobacteriaceae isolated from the sewage of a secondary hospital in Ribeirão Preto, a city in southeastern Brazil. The strains were isolated by membrane filtration and identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF). The antimicrobial susceptibility profile was performed by disk diffusion. Polymerase chain reaction (PCR) assays were used to detect virulence genes among the strains. Twenty-eight isolates were obtained, with Klebsiella pneumoniae being the predominant species (71.4%, n = 20). All isolates were classified as multidrug-resistant, including four isolates that were non-susceptible to at least 50% of the tested antibiotics. All isolates were also non-susceptible to cefuroxime and sulfonamides antibiotics; however, they were susceptible to norfloxacin, ofloxacin, amikacin, gentamicin, netilmicin, ertapenem, cefazolin, cefaclor, and cefotetan. The virulence genes ycfM, fimH, mrkD, kfu, and entB were detected in several isolates. Our study showed that even in a secondary hospital, without the routine of major surgeries and intensive care admissions, the hospital sewage can harbor a high percentage of multidrug-resistant bacteria with pathogenic potential. This leads to the worrying risk of public health and environmental contamination.


Assuntos
Enterobacteriaceae , Esgotos , Testes de Sensibilidade Microbiana , Brasil , Monitoramento Ambiental , Antibacterianos/farmacologia , Hospitais , beta-Lactamases/genética
19.
Environ Monit Assess ; 194(10): 782, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098842

RESUMO

Hospital sewage is considered an environment with the potential to favor the spread and increase of multidrug-resistant bacteria (MDR). The increase in antimicrobial resistance is one of the greatest global threats today. Therefore, this study aimed to evaluate the profile of antimicrobial susceptibility and virulence factors in Enterobacteriaceae isolated from the sewage of a tertiary hospital located in southeastern Brazil. For bacterial isolation, membrane filtering, serial dilution, and spread-plate techniques were used. The bacterial isolates were identified using the MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) technique. Antimicrobial susceptibility profile was performed by disk-diffusion test. Virulence genes were screened by Polymerase Chain Reaction (PCR) and the hypermucoviscosity phenotype by string test. In total, 13 enterobacteria distributed in three species were identified (Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii) and 76.9% (n = 10) were classified as MDR. Two K. pneumoniae demonstrated the hypermucoviscosity phenotype. The virulence genes ycfM and entB were detected in all K. pneumoniae isolates (other genes found were fimH, mrkD, and kfu). The results indicated that the sewage from the analyzed hospital receives MDR bacteria and has the potential to contaminate and spread through the environment.


Assuntos
Anti-Infecciosos , Infecções por Klebsiella , Brasil , Enterobacteriaceae/genética , Monitoramento Ambiental , Escherichia coli , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Esgotos , Centros de Atenção Terciária
20.
Clin Infect Dis ; 73(9): 1634-1641, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33970214

RESUMO

BACKGROUND: Rifampin is generally advised in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin remains a matter of debate. We evaluated the outcome of patients treated with and without rifampin, and analyzed the influence of timing, dose and co-antibiotic. METHODS: Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death or the need for suppressive antimicrobial treatment. RESULTS: A total of 669 patients were analyzed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P < .001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P < .001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 - 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone or clindamycin (OR 10.1, 95% CI 5.65 - 18.2) and the start of rifampin within 5 days after surgical debridement (OR 1.96, 95% CI 1.08 - 3.65) were predictors of treatment failure. The dosing of rifampin had no effect on outcome. CONCLUSIONS: Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged, but requires further investigation.


Assuntos
Infecções Relacionadas à Prótese , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Desbridamento , Humanos , Infecções Relacionadas à Prótese/tratamento farmacológico , Estudos Retrospectivos , Rifampina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus , Resultado do Tratamento
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