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1.
Chem Mater ; 36(15): 7274-7282, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39156719

RESUMO

Metal-organic framework (MOF)-74 is known for its effectiveness in selectively capturing carbon dioxide (CO2). Especially the Zn and Cu versions of MOF-74 show high efficiency of this material for CO2. However, the activation of this MOF, which is a crucial step for its utilization, is so far not well understood. Here, we are closing the knowledge gap by examining the activation using, for the first time in the MOF, three-dimensional electron diffraction (3DED) during in situ heating. The use of state-of-the-art direct electron detectors enables rapid acquisition and minimal exposure times, therefore minimizing beam damage to the very electron beam-sensitive MOF material. The activation process of Zn-MOF-74 and Cu-MOF-74 is systematically studied in situ, proving the creation of open metal sites. Differences in thermal stability between Zn-MOF-74 and Cu-MOF-74 are attributed to the strength of the metal-oxygen bonds and Jahn-Teller distortions. In the case of Zn-MOF-74, we observe previously unknown remaining electrostatic potentials inside the MOF pores, which indicate the presence of remaining atoms that might impede gas flow throughout the structure when using the MOF for absorption purposes. We believe our study exemplifies the significance of employing advanced characterization techniques to enhance our material understanding, which is a crucial step for unlocking the full potential of MOFs in various applications.

2.
Proc Natl Acad Sci U S A ; 121(10): e2310852121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38416678

RESUMO

Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.


Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Animais , Humanos , Enterococcus/genética , Antibacterianos/farmacologia , Enterococcus faecium/genética , Enterococcus faecalis/genética , Filogenia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
3.
Int J Nurs Sci ; 11(1): 46-56, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352284

RESUMO

Objectives: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) patients experience a lower quality of life, frequent exacerbations, and worse pulmonary function. Environmental management is essential in a complex chronic condition, as pollutant exposure can worsen symptoms and increase morbidity and mortality. We aimed to identify evidence that informs nursing interventions in promoting self-management of air quality in asthmatic people with COPD. Methods: We conducted an integrative review in March of 2023. We searched the databases CINAHL, MEDLINE, Academic Search Complete, Cochrane Database of Systematic Reviews (CDSR), Scopus, Web of Science, Joanna Briggs Institute (JBI) Evidence-Based Practice Database, and Google Scholar. We included articles whose participants were adults with asthma, COPD, or both; the intervention was air quality management and the outcome of any exacerbations. We excluded editorials, letters, commentaries, opinion papers, position papers, study protocols, conference abstracts, and reviews. Data extraction and synthesis were performed, categorizing interventions according to nursing actions. Methodological quality assessment was conducted using the JBI Critical Appraisal Checklist tools. The review protocol was registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/5Y4KW). Results: We included five articles from different countries. The interventions promoting air quality self-management for individuals with asthma and COPD included vigilance interventions (health professional regular visits, assessment of symptoms), monitoring interventions (measurement of indoor and outdoor trigger factors), and educational interventions (air quality alerts, allergen avoidance). Policy interventions such as smoke-free policies and comprehensive strategies to improve air quality were also identified. These areas of focus represent critical components of nurses' interventions and can integrate the fundamental patterns of knowing in nursing. Although the studies reveal heterogeneous interventions and the methodological quality is variable, these interventions showed potential for preventing exacerbations, reducing emergency department visits, and minimizing hospitalizations. Conclusions: The study emphasizes the need for a comprehensive approach involving nurses in multidisciplinary teams to air quality self-management. They can use these results to inform their interventions and ways of knowing, benefiting individuals with asthma and COPD. Further research is needed to expand the evidence base and refine these interventions.

4.
Org Biomol Chem ; 22(7): 1500-1513, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38294067

RESUMO

Inspired by the pharmacological interest generated by 6-substituted purine roscovitine for cancer treatment, 5-aminoimidazole-4-carboxamidine precursors containing a cyanamide unit were prepared by condensation of 5-amino-N-cyanoimidazole-4-carbimidoyl cyanides with a wide range of primary amines. When these amidine precursors were combined with acids, a fast cascade cyclization occurred at room temperature, affording new 6,8-diaminopurines with the N-3 and N-6 substituents changed relatively to the original positions they occupied in the amidine and imidazole moieties of precursors. The efficacy and wide scope of this method was well demonstrated by an easy and affordable synthesis of 22 6,8-diaminopurines decorated with a wide diversity of substituents at the N-3 and N-6 positions of the purine ring. Preliminary in silico and in vitro assessments of these 22 compounds were carried out and the results showed that 13 of these tested compounds not only exhibited IC50 values between 1.4 and 7.5 µM against the colorectal cancer cell line HCT116 but also showed better binding energies than known inhibitors in docking studies with different cancer-related target proteins. In addition, good harmonization observed between in silico and in vitro results strengthens and validates this preliminary evaluation, suggesting that these novel entities are good candidates for further studies as new anticancer agents.


Assuntos
Antineoplásicos , Estrutura Molecular , Relação Estrutura-Atividade , Antineoplásicos/química , Ciclização , Imidazóis/farmacologia , Purinas/farmacologia , Amidinas/farmacologia , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células
5.
Talanta ; 269: 125482, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042146

RESUMO

Attenuated Total Reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is an emerging technology in the medical field. Blood D-dimer was initially studied as a marker of the activation of coagulation and fibrinolysis. It is mainly used as a potential diagnosis screening test for pulmonary embolism or deep vein thrombosis but was recently associated with COVID-19 severity. This study aimed to evaluate the use of ATR-FTIR spectroscopy with machine learning to classify plasma D-dimer concentrations. The plasma ATR-FTIR spectra from 100 patients were studied through principal component analysis (PCA) and two supervised approaches: genetic algorithm with linear discriminant analysis (GA-LDA) and partial least squares with linear discriminant (PLS-DA). The spectra were truncated to the fingerprint region (1800-1000 cm-1). The GA-LDA method effectively classified patients according to D-dimer cutoff (≤0.5 µg/mL and >0.5 µg/mL) with 87.5 % specificity and 100 % sensitivity on the training set, and 85.7 % specificity, and 95.6 % sensitivity on the test set. Thus, we demonstrate that ATR-FTIR spectroscopy might be an important additional tool for classifying patients according to D-dimer values. ATR-FTIR spectral analyses associated with clinical evidence can contribute to a faster and more accurate medical diagnosis, reduce patient morbidity, and save resources and demand for professionals.


Assuntos
Espectroscopia de Infravermelho com Transformada de Fourier , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise de Fourier , Análise Discriminante , Análise de Componente Principal , Proteínas Mutadas de Ataxia Telangiectasia
6.
Nanomaterials (Basel) ; 13(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37446436

RESUMO

During the last few decades, major advances have been made in photovoltaic systems based on Cu(In,Ga)Se2 chalcopyrite. However, the most efficient photovoltaic cells are processed under high-energy-demanding vacuum conditions. To lower the costs and facilitate high-throughput production, printing/coating processes are proving to be effective solutions. This work combined printing, coating, and chemical bath deposition processes of photoabsorber, buffer, and transparent conductive layers for the development of solution-processed photovoltaic systems. Using a sustainable approach, all inks were formulated using water and ethanol as solvents. Screen printing of the photoabsorber on fluorine-doped tin-oxide-coated glass followed by selenization, chemical bath deposition of the cadmium sulfide buffer, and final sputtering of the intrinsic zinc oxide and aluminum-doped zinc oxide top conductive layers delivered a 6.6% maximum efficiency solar cell, a record for screen-printed Cu(In,Ga)Se2 solar cells. On the other hand, the all-non-vacuum-processed device with spray-coated intrinsic zinc-oxide- and tin-doped indium oxide top conductive layers delivered a 2.2% efficiency. The given approaches represent relevant steps towards the fabrication of sustainable and efficient Cu(In,Ga)Se2 solar cells.

7.
bioRxiv ; 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37293047

RESUMO

Enterococci are commensal gut microbes of most land animals. They diversified over hundreds of millions of years adapting to evolving hosts and host diets. Of over 60 known enterococcal species, Enterococcus faecalis and E. faecium uniquely emerged in the antibiotic era among leading causes of multidrug resistant hospital-associated infection. The basis for the association of particular enterococcal species with a host is largely unknown. To begin deciphering enterococcal species traits that drive host association, and to assess the pool of Enterococcus-adapted genes from which known facile gene exchangers such as E. faecalis and E. faecium may draw, we collected 886 enterococcal strains from nearly 1,000 specimens representing widely diverse hosts, ecologies and geographies. This provided data on the global occurrence and host associations of known species, identifying 18 new species in the process expanding genus diversity by >25%. The novel species harbor diverse genes associated with toxins, detoxification, and resource acquisition. E. faecalis and E. faecium were isolated from a wide diversity of hosts highlighting their generalist properties, whereas most other species exhibited more restricted distributions indicative of specialized host associations. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades as well as genes associated with range expansion, such as B-vitamin biosynthesis and flagellar motility. Collectively, this work provides an unprecedentedly broad and deep view of the genus Enterococcus, potential threats to human health, and new insights into its evolution.

8.
Braz J Infect Dis ; 27(3): 102771, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37088105

RESUMO

BACKGROUND: In the initial phases of the COVID-19 pandemic, strategies adopted to reduce the dissemination of SARS-CoV-2 relied on non-pharmacological interventions, including physical distancing. Mobility restrictions affected the availability and quality of care for many health conditions, including sexually transmitted infections. OBJECTIVE: To investigate the impact of the COVID-19 pandemic mobility restriction on syphilis and HIV testing in outpatient settings. METHODS: In this study, we collected the weekly number of syphilis and HIV tests performed in a referent laboratory in São Paulo, Brazil, as well as the percentage of positive tests between January 2019 and December 2021. We also retrieved data on retail and recreation mobility in São Paulo city using Google COVID-19 Community Mobility Reports. We explored the association between populational mobility and the number of weekly tests and the association between the number of weekly tests and the percentage of positive results during the pandemic period. The analyses were conducted separately for syphilis and HIV tests. RESULTS: We found that mobility restrictions during the COVID-19 pandemic have been associated with a significant decrease in both syphilis and HIV tests performed in outpatient settings. We also observed that the number of tests performed was inversely associated with the percentage of positive results for syphilis; this association was also apparent for HIV tests in the first wave of the pandemic in the graphic analysis. CONCLUSION: Taken together, our findings suggest an indirect impact of COVID-19 pandemic-related mobility restrictions on the uptake of diagnostic tests for HIV and syphilis and the potential adoption of targeted-testing strategies. Understanding the extent and complexity of COVID-19 aftermaths on specific conditions and communities is essential to build strategies to mitigate the long-term consequences of COVID-19.


Assuntos
COVID-19 , Infecções por HIV , Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/epidemiologia , COVID-19/epidemiologia , COVID-19/complicações , Pandemias , Brasil/epidemiologia , Pacientes Ambulatoriais , SARS-CoV-2 , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/complicações
9.
Curr Microbiol ; 80(5): 136, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36914801

RESUMO

It is known that probiotic microorganisms play important roles in the composition of the intestinal microbiota. Also, probiotics can affect the paracellular and transcellular transport mechanisms performed by intestinal cells. The aim of this work was to evaluate the effect of the potential probiotic Bacillus subtilis KM0 on the profile of the gut microbiota and transcription of genes related to intestinal transport of zebrafish (Danio rerio). Zebrafish was exposed by immersion to B. subtilis KM0 for 48 h, and the intestines were collected for metataxonomic analysis and transcription of genes related to transcellular and paracellular transports. Although exposure to B. subtilis changed the intestinal microbiota profile of zebrafish, the diversity indices were not altered. A decrease in the number of genera of potentially pathogenic bacteria (Flavobacterium, Plesiomonas, and Pseudomonas) and downregulation in transcription of transcellular transport genes (cubn and amn) were observed. B. subtilis KM0 strain had the expected probiotic effect, by interfering with the proliferation of potentially pathogenic bacteria and decreasing the transcription of genes codifying for signals involved with a mechanism that can be used for invasion by pathogens. The present study demonstrated that, even with a short-term exposure, a bacterium with probiotic potential such as the KM0 strain of B. subtilis can modify the profile of the host's intestinal microbiota, with an impact on the regulation of intestinal genes related to mechanisms that can be used for invasion by pathogenic bacteria.


Assuntos
Microbioma Gastrointestinal , Probióticos , Animais , Bacillus subtilis/genética , Peixe-Zebra/microbiologia , Intestinos/microbiologia
10.
Sci Transl Med ; 15(686): eabn3464, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36867683

RESUMO

As mRNA vaccines have proved to be very successful in battling the coronavirus disease 2019 (COVID-19) pandemic, this new modality has attracted widespread interest for the development of potent vaccines against other infectious diseases and cancer. Cervical cancer caused by persistent human papillomavirus (HPV) infection is a major cause of cancer-related deaths in women, and the development of safe and effective therapeutic strategies is urgently needed. In the present study, we compared the performance of three different mRNA vaccine modalities to target tumors associated with HPV-16 infection in mice. We generated lipid nanoparticle (LNP)-encapsulated self-amplifying mRNA as well as unmodified and nucleoside-modified non-replicating mRNA vaccines encoding a chimeric protein derived from the fusion of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D (gDE7). We demonstrated that single low-dose immunizations with any of the three gDE7 mRNA vaccines induced activation of E7-specific CD8+ T cells, generated memory T cell responses capable of preventing tumor relapses, and eradicated subcutaneous tumors at different growth stages. In addition, the gDE7 mRNA-LNP vaccines induced potent tumor protection in two different orthotopic mouse tumor models after administration of a single vaccine dose. Last, comparative studies demonstrated that all three gDE7 mRNA-LNP vaccines proved to be superior to gDE7 DNA and gDE7 recombinant protein vaccines. Collectively, we demonstrated the immunogenicity and therapeutic efficacy of three different mRNA vaccines in extensive comparative experiments. Our data support further evaluation of these mRNA vaccines in clinical trials.


Assuntos
Vacinas Anticâncer , Neoplasias , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinas de DNA , Animais , Feminino , Camundongos , Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Imunização , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/genética , Proteínas Recombinantes , RNA Mensageiro/genética
11.
Environ Sci Pollut Res Int ; 30(18): 52485-52497, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36840876

RESUMO

The consumption of açaí fruit (Euterpe oleracea) has largely increased worldwide, resulting in a significant increase in the demand for its pulp. As a result, the small producing communities end up with large amounts of açaí endocarp residues, creating local environmental pollution problems. Therefore, chemical and physical routes were investigated for producing açaí endocarp adsorbents to propose a locally viable solution for this problem. The adsorption properties of the produced biochars were tested for clonazepam (CZM) removal, and the toxicity of the final solutions was evaluated. The results revealed that the chemical route generated biochar with about twice the surface area and pore volume (762 m2 g-1 and 0.098 cm3 g-1) than the physical route (498 m2 g-1 and 0.048 cm3 g-1). Furthermore, the Sips isotherm better described the CZM adsorption equilibrium for both biochars, with qs values of 26.94 and 61.86 mg g-1 for the physical- and chemical-activated adsorbents. Moreover, recycling studies were performed, and the chemical-activated biochar was stable for up to three cycles, reaching removal rates superior to 80%. Besides, the final toxicity decreased after the adsorptive treatment. Therefore, chemical activation can be used as a simple and effective method for producing stable and compelling adsorbents as an elegant way of adding value to the residues from açaí production, helping solve local environmental problems.


Assuntos
Euterpe , Euterpe/química , Clonazepam , Adsorção , Carvão Vegetal/química
12.
Clin Oral Investig ; 27(4): 1329-1342, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36790626

RESUMO

OBJECTIVES: This systematic review and meta-analysis aimed to address whether non-surgical periodontal therapy (NSPT) can affect insulin resistance, estimated by the homeostasis model assessment (HOMA), in adults with prediabetes or type 2 diabetes mellitus and periodontitis. MATERIALS AND METHODS: Six electronic databases and the gray literature were systematically searched for interventional studies reporting NSPT effect on insulin resistance. Seven studies met the eligibility criteria to be synthesized in the qualitative analysis, six reporting change in HOMA-IR, three reporting change in HOMA-%S, and two in HOMA-ß. Among them, four were pooled in a meta-analysis of standardized mean difference (SMD) of HOMA-IR; comparing pre- and post-intervention values, three were pooled considering HOMA-%S as outcome, and two studies were summarized considering SMD of HOMA-%S between intervention and control groups. HOMA-ß results were qualitatively synthetized. RESULTS: With low level of certainty, NSPT significantly reduced HOMA-IR, when compared with pre-intervention data (SMD, -0.35, 95% CI -0.63 to 0.07, p=0.02). There were no significant changes in HOMA-%S or in HOMA-ß scores. The level of certainty was very low and moderate, respectively. CONCLUSIONS: Assertions about a causal link between NSPT and insulin resistance are weak and conflicting, although our more robust results point out to the absence of effect. . CLINICAL RELEVANCE: Because further high-quality studies assessing the relationship between periodontitis and insulin resistance are need, the findings of the current systematic review are limited to give recommendations for clinicians. However, while identifying a lack of research in humans with T2D concerning periodontitis and insulin resistance, this study reinforces the need of multicenter well-designed randomized clinical trials.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Periodontite , Estado Pré-Diabético , Adulto , Humanos , Diabetes Mellitus Tipo 2/terapia , Periodontite/terapia , Estado Pré-Diabético/terapia , Estudos Multicêntricos como Assunto
13.
J Clin Periodontol ; 50(1): 11-21, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36053828

RESUMO

AIM: To assess the effect of periodontal treatment on HbA1c and diagnostic parameters of patients with metabolic syndrome (MetS). MATERIALS AND METHODS: One hundred and fifty-eight patients with MetS and moderate and severe periodontitis were included. They were randomized into a test group (n = 79), which received non-surgical periodontal treatment, and a control group (n = 79), which received no treatment. Medical treatment was delivered to both groups. Clinical periodontal, anthropometric and serological parameters were assessed at baseline, 3 and 6 months. The main outcome was glycated haemoglobin (HbA1c) levels, and the secondary outcomes were changes in the MetS parameters, C-reactive protein (CRP) and HOMA indexes. RESULTS: Significant reductions in all periodontal parameters were observed in the test group, compared with the control group, at 3 and 6 months (p < .001). HbA1c levels, MetS parameters, CRP and HOMA indexes showed no significant differences between the test group and the control group at 3 and 6 months. CONCLUSIONS: Periodontal treatment led to a substantial reduction in periodontal inflammation, although there was no significant effect on the parameters used for MetS diagnosis in patients with early diagnosed and well-controlled MetS.


Assuntos
Periodontite Crônica , Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Humanos , Hemoglobinas Glicadas , Aplainamento Radicular , Raspagem Dentária , Síndrome Metabólica/complicações , Síndrome Metabólica/terapia , Periodontite Crônica/complicações , Periodontite Crônica/terapia , Proteína C-Reativa/análise , Diabetes Mellitus Tipo 2/complicações
14.
Braz. j. infect. dis ; 27(3): 102771, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1447666

RESUMO

Abstract Background In the initial phases of the COVID-19 pandemic, strategies adopted to reduce the dissemination of SARS-CoV-2 relied on non-pharmacological interventions, including physical distancing. Mobility restrictions affected the availability and quality of care for many health conditions, including sexually transmitted infections. Objective To investigate the impact of the COVID-19 pandemic mobility restriction on syphilis and HIV testing in outpatient settings. Methods In this study, we collected the weekly number of syphilis and HIV tests performed in a referent laboratory in São Paulo, Brazil, as well as the percentage of positive tests between January 2019 and December 2021. We also retrieved data on retail and recreation mobility in São Paulo city using Google COVID-19 Community Mobility Reports. We explored the association between populational mobility and the number of weekly tests and the association between the number of weekly tests and the percentage of positive results during the pandemic period. The analyses were conducted separately for syphilis and HIV tests. Results We found that mobility restrictions during the COVID-19 pandemic have been associated with a significant decrease in both syphilis and HIV tests performed in outpatient settings. We also observed that the number of tests performed was inversely associated with the percentage of positive results for syphilis; this association was also apparent for HIV tests in the first wave of the pandemic in the graphic analysis. Conclusion Taken together, our findings suggest an indirect impact of COVID-19 pandemic-related mobility restrictions on the uptake of diagnostic tests for HIV and syphilis and the potential adoption of targeted-testing strategies. Understanding the extent and complexity of COVID-19 aftermaths on specific conditions and communities is essential to build strategies to mitigate the long-term consequences of COVID-19.

15.
Molecules ; 29(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38202672

RESUMO

Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by persistent fear responses and altered neurotransmitter functioning due to traumatic experiences. Stress predominantly affects glutamate, a neurotransmitter crucial for synaptic plasticity and memory formation. Activation of the N-Methyl-D-Aspartate glutamate receptors (NMDAR) can trigger the formation of a complex comprising postsynaptic density protein-95 (PSD95), the neuronal nitric oxide synthase (nNOS), and its adaptor protein (NOS1AP). This complex is pivotal in activating nNOS and nitric oxide (NO) production, which, in turn, activates downstream pathways that modulate neuronal signaling, including synaptic plasticity/transmission, inflammation, and cell death. The involvement of nNOS and NOS1AP in the susceptibility of PTSD and its comorbidities has been widely shown. Therefore, understanding the interplay between stress, fear, and NO is essential for comprehending the maintenance and progression of PTSD, since NO is involved in fear acquisition and extinction processes. Moreover, NO induces post-translational modifications (PTMs), including S-nitrosylation and nitration, which alter protein function and structure for intracellular signaling. Although evidence suggests that NO influences synaptic plasticity and memory processing, the specific role of PTMs in the pathophysiology of PTSD remains unclear. This review highlights pathways modulated by NO that could be relevant to stress and PTSD.


Assuntos
Óxido Nítrico , Transtornos de Estresse Pós-Traumáticos , Humanos , Medo , Ácido Glutâmico , Neurotransmissores , Proteínas Adaptadoras de Transdução de Sinal
16.
Pathogens ; 11(12)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36558768

RESUMO

Mammary pathogenic E. coli (MPEC) is one of the main pathogens of environmental origin responsible for causing clinical mastitis worldwide. Even though E. coli are strongly associated with transient or persistent mastitis and the economic impacts of this disease, the virulence factors involved in the pathogenesis of MPEC remain unknown. Our aim was to characterize 110 MPEC isolates obtained from the milk of cows with clinical mastitis, regarding the virulence factor-encoding genes present, adherence patterns on HeLa cells, and antimicrobial resistance profile. The MPEC isolates were classified mainly in phylogroups A (50.9%) and B1 (38.2%). None of the isolates harbored genes used for diarrheagenic E. coli classification, but 26 (23.6%) and 4 (3.6%) isolates produced the aggregative or diffuse adherence pattern, respectively. Among the 22 genes investigated, encoding virulence factors associated with extraintestinal pathogenic E. coli pathogenesis, fimH (93.6%) was the most frequent, followed by traT (77.3%) and ompT (68.2%). Pulsed-field gel electrophoresis analysis revealed six pulse-types with isolates obtained over time, thus indicating persistent intramammary infections. The genes encoding beta-lactamases detected were as follows: blaTEM (35/31.8%); blaCTX-M-2/blaCTX-M-8 (2/1.8%); blaCTX-M-15 and blaCMY-2 (1/0.9%); five isolates were classified as extended spectrum beta-lactamase (ESBL) producers. As far as we know, papA, shf, ireA, sat and blaCTX-M-8 were detected for the first time in MPEC. In summary, the genetic profile of the MPEC studied was highly heterogeneous, making it impossible to establish a common genetic profile useful for molecular MPEC classification. Moreover, the detection of ESBL-producing isolates is a serious public health concern.

17.
An Acad Bras Cienc ; 94(4): e20210190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36228216

RESUMO

Duchenne muscular dystrophy (DMD) is a severe disease with no cure caused by a genetic abnormality, promoting progressive muscle degeneration. Corticosteroids are used drugs in treatment associated with adverse effects. The extract of Miconia ferruginata (Melastomataceae) (MF) has demonstrated potent antioxidant and anti-inflammatory potential in vitro. This study used a DMD model (mdx) to determine the toxic dose of this plant and found a possible non-toxic dose with therapeutic effects. The mdx groups received an intraperitoneal injection of 0 (control group), 50, 100, 200, 300, and 2000 mg kg-1 of the aqueous leaf extract following a single-dose acute toxicity protocol and were observed for 14 days. The range of toxicity of the extract and LD50 were determined. Histopathological analysis, the quantification of fibrosis, and immunohistochemical analysis of the tissues were performed. The results demonstrated that 2000 mg kg-1 was highly toxic, inducing histopathological changes in the tissues evaluated, with 100% mortality in 48 hours. The other doses caused no behavioral changes or signs of toxicity. The MF extract led reduction in histopathological changes, fibrosis, and inflammation, a reduction in HSP70 and an increase in MCL-1 proteins. Doses of 50-200 mg kg-1 demonstrated regenerative tissue and anti-inflammatory potential.


Assuntos
Melastomataceae , Distrofia Muscular de Duchenne , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Modelos Animais de Doenças , Fibrose , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/tratamento farmacológico , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/uso terapêutico , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade
18.
J Chem Phys ; 157(9): 094706, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36075730

RESUMO

The present work attempts to systematically explore the surfactant sorption at liquid-liquid interfaces with coarse-grained models targeting thermodynamic properties of reference liquid solutions. We employ dissipative particle dynamics with soft-core forcefield tested against experimental data on micellization of surfactants in water, and the previous results are reproduced in this work. We consider three different nonionic surfactants: hexaethylene glycol monododecyl ether (C12E6), 2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol) known as Triton X-100 (TX-100), and two alkyl glucoside surfactants (CnG1) with n-alkane tail fragments and a saccharide hydrophilic head at decane-water and toluene-water interfaces. For TX-100, we composed a model based on the literature forcefield and found good agreement with the experimental critical micelle concentrations (CMCs). The head-head interactions are of different origins for different surfactant groups: entropic repulsion between ethylene oxide chains of C12E6 and TX-100, and more chemically specific and complex interactions between the maltose heads of alkyl glucosides. We interpret our results with the Redlich-Peterson equation of monolayer adsorption in order to relate the adsorption to the bulk concentration of the surfactant and the interfacial tension. The densities of the adsorbed monolayer at CMC mostly agree with the experimental data, and a reasonable agreement was obtained for the interfacial tension at CMC. At the same time, we found significant discrepancies between the simulated and experimental adsorption isotherms. We explain them by the oversimplified forcefield: when the parameters are fitted to the free energies of bulk solutions, they may not correctly reproduce the interfacial free energies.


Assuntos
Micelas , Tensoativos , Adsorção , Tensão Superficial , Tensoativos/química , Água/química
19.
Front Genet ; 13: 903201, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159973

RESUMO

Silverside fish inhabit marine coastal waters, coastal lagoons, and estuarine regions in southern South America. Although silversides are not fully adapted to freshwater, they can tolerate a wide range of salinity variations. MicroRNAs (miRNAs) are a class of ∼22 nucleotide noncoding RNAs, which are crucial regulators of gene expression at post-transcriptional level. Current data indicate that miRNAs biogenesis is altered by situations of environmental stress, thereby altering the expression of target mRNAs. Foremost, the silversides were acutely exposed to 30 g.L-1 of salt to reveal in which tissue miR-429 could be differentially expressed. Thus, fish were acclimated to freshwater (0 g.L-1) and to brackish water (10 g.L-1), and then exposed to opposite salinity treatment. Here, we reveal that miR-429, a gill-enriched miRNA, emerges as a prime osmoregulator in silversides. Taken together, our findings suggest that miR-429 is an endogenous regulator of osmotic stress, which may be developed as a biomarker to assist silverside aquaculture.

20.
Pharmacol Biochem Behav ; 220: 173468, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36174752

RESUMO

Major depressive disorder (MDD) is the most prevalent mood disorder globally. Most antidepressants available for the treatment of MDD increase the concentration of monoamines in the synaptic cleft. However, such drugs have a high latency time to obtain benefits. Thus, new antidepressants with fast action and robust efficacy are very important. This study evaluated the effects of escitalopram, ketamine, and probiotic Bifidobacterium infantis in rats submitted to the maternal deprivation (MD). MD rats received saline, escitalopram, ketamine, or probiotic for 10, 30, or 50 days, depending on the postnatal day (PND):21, 41, and 61. Following behavior, this study examined the integrity of the blood-brain barrier (BBB) and oxidative stress markers. MD induced depressive-like behavior in females with PND21 and males with PND61. All treatments reversed depressive-like behavior in females and escitalopram and ketamine in males. MD induced an increase in the permeability of the BBB, an imbalance between oxidative stress and antioxidant defenses. Treatments regulated the oxidative damage and the integrity of the BBB induced by MD. The treatment with escitalopram, ketamine, or probiotics may prevent behavioral and neurochemical changes associated with MDD, depending on the developmental period and gender.


Assuntos
Antidepressivos , Transtorno Depressivo Maior , Caracteres Sexuais , Estresse Psicológico , Animais , Feminino , Masculino , Ratos , Antidepressivos/uso terapêutico , Antioxidantes/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Ketamina , Ratos Wistar , Estresse Psicológico/tratamento farmacológico , Escitalopram
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