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1.
J Biol Chem ; 299(3): 103004, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36775130

RESUMO

SARS-CoV-2 is the causative agent of COVID-19. The main viral protease (Mpro) is an attractive target for antivirals. The clinically approved drug nirmatrelvir and the clinical candidate ensitrelvir have so far showed great potential for treatment of viral infection. However, the broad use of antivirals is often associated with resistance generation. Herein, we enzymatically characterized 14 naturally occurring Mpro polymorphisms that are close to the binding site of these antivirals. Nirmatrelvir retained its potency against most polymorphisms tested, while mutants G143S and Q189K were associated with diminished inhibition constants. For ensitrelvir, diminished inhibition constants were observed for polymorphisms M49I, G143S, and R188S, but not for Q189K, suggesting a distinct resistance profile between inhibitors. In addition, the crystal structures of selected polymorphisms revealed interactions that were critical for loss of potency. In conclusion, our data will assist the monitoring of potential resistant strains, support the design of combined therapy, as well as assist the development of the next generation of Mpro inhibitors.


Assuntos
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/genética , Antivirais/farmacologia , Lactamas , Leucina , Nitrilas , Inibidores de Proteases/farmacologia
2.
Microb Pathog ; 189: 106577, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367848

RESUMO

Neospora caninum is a protozoan parasite with worldwide incidence, acting as a major cause of reproductive failures in ruminants and neuromuscular symptoms in dogs. Macrophage Migration Inhibitory Factor (MIF) is produced by several cell types and exhibits a central role in immune responses against intracellular pathogens. The present study aimed to comprehend the role of MIF in the relationship between N. caninum and its host. We used in vivo, in vitro and ex vivo experiments in a model of infection based on genetically deficient mice to analyze the infection kinetics and inflammatory markers. MIF production was measured in response to N. caninum during the acute and chronic phases of the infection. While Mif-/- mice survived lethal doses of NcLiv tachyzoites, sublethal infections in these mice showed that parasite burden was controlled in target tissues, alongside with reduced inflammatory infiltrates detected in lung and brain sections. TNF was increased at the initial site of the infection in genetically deficient mice and the MIF-dependent reduction was confirmed in vitro with macrophages and ex vivo with primed spleen cells. In sum, MIF negatively regulated host immunity against N. caninum, favoring disease progression.


Assuntos
Coccidiose , Fatores Inibidores da Migração de Macrófagos , Neospora , Animais , Camundongos , Cães , Fatores Inibidores da Migração de Macrófagos/genética , Coccidiose/veterinária
3.
Chemistry ; 30(12): e202303771, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38118132

RESUMO

This work explores the potential of carbon dots as a fluorescent probe in the determination of heavy ions and as an electrochemical biosensor. It also discusses how carbon dots can be introduced into the Fricke solution to potentially serve as an ionizing radiation sensor. The study presents a novel tissue equivalent dosimeter carbon dots-based as an ionizing radiation sensor. The methodology for the synthesis of Nitrogen-doped Carbon Dots N-CDs and the characterization of the material are described. The results show that the N-CDs have a high sensitivity to ionizing radiation and can be used as a dosimeter for radiation detection. The study also discusses the limitations and challenges of using carbon dots as a dosimeter for ionizing radiation. Overall, this study provides valuable insights into the potential applications of carbon dots in different fields and highlights the importance of further research in this area.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Pontos Quânticos/química , Carbono/química , Dosímetros de Radiação , Nitrogênio/química , Corantes Fluorescentes/química
4.
Mol Psychiatry ; 28(2): 553-563, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35701598

RESUMO

People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.


Assuntos
COVID-19 , Disfunção Cognitiva , Adulto , Humanos , COVID-19/complicações , Neuroimagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Imageamento por Ressonância Magnética
5.
Soft Matter ; 20(10): 2310-2320, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38363303

RESUMO

We investigate the collective behavior of sterically interacting self-propelled particles confined in a harmonic potential. Our theoretical and numerical study unveils the emergence of distinctive collective polar organizations, revealing how different levels of interparticle torques and noise influence the system. The observed phases include the shear-banded vortex, where the system self organizes in two concentric bands rotating in opposite directions around the potential center; the uniform vortex, where the two bands merge into a close packed configuration rotating uniformly as a quasi-rigid body; and the orbiting polar state, characterized by parallel orientation vectors and the cluster revolving around the potential center, without rotation, as a rigid body. Intriguingly, at lower filling fractions, the vortex and polar phases merge into a single phase where the trapped cluster breaks into smaller polarized clusters, each one orbiting the potential center as a rigid body.

6.
J Geriatr Psychiatry Neurol ; : 8919887241237223, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445606

RESUMO

BACKGROUND: Depression and anxiety are non-motor symptoms of Parkinson's disease (PD). Physical exercise is a promising approach to reducing neuropsychological burden. We aimed to comprehensively synthesize evidence regarding the use of exercise for treating depression and anxiety symptoms in PD. METHODS: Systematic review and meta-analysis following PRISMA recommendations. Searches on PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Physiotherapy Evidence Database (PEDro) was conducted. The random-effects model was employed for all analyses with the standardized mean difference as the effect estimate. RESULTS: Fifty records were retrieved, but only 17 studies met the criteria for the meta-analyses. A moderate to large effect was observed for depression (-.71 [95% CI = -.96 to -.46], 11 studies, 728 individuals), and a small to moderate effect for anxiety (-.39 [95% CI = -.65 to -.14], 6 studies, 241 individuals), when comparing exercise to non-exercise controls. Subgroup analysis revealed significant effects from aerobic (-.95 [95% CI = -1.60, -.31]), mind-body (-1.85 [95% CI = -2.63, -1.07]), and resistance modalities (-1.61 [95% CI = -2.40, -.83]) for depression, and from mind-body (-.67 [95% CI = -1.19 to -.15]) and resistance exercises (-1.00 [95% CI = -1.70 to -.30]) for anxiety. CONCLUSION: Physical exercise has a relevant clinical impact on depression and anxiety in PD. We discuss the level of the evidence, the methodological limitations of the studies, and give recommendations.

7.
BMC Pediatr ; 24(1): 447, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992690

RESUMO

BACKGROUND: The aim of our study was to evaluate the impact of the ActTeens Program on physical activity and health-related physical fitness among adolescents in Brazil. METHODS: The "ActTeens Program" was conducted using a cluster-randomized controlled trial during 24-week school term. The sample consisted of 317 adolescents (52.7% girls; 13.61 ± 0.70 years) from four secondary schools that were randomly assigned to intervention group (N = 169) or control group (N = 148). This school-based physical activity (PA) intervention involved two components: (i) structured physical activity sessions delivered within physical education (PE) and (ii) healthy lifestyle guidance (mHealth). The primary outcome was PA assessed using Physical Activity Questionnaire for Adolescents (PAQ-A); secondary outcomes included muscular (MF) and cardiorespiratory fitness (CRF) assessed using 90-push-up, handgrip dynamometer, standing long jump, and 20 m PACER shuttle run test. Assessments were conducted at baseline, 12- and 24-week. Intervention effects were assessed using linear mixed models (LMM). RESULTS: For the primary outcome (PA), no significant group-by-time effects were observed for physical education based-PA (0.3 score; 95%CI: -0.1; 0.6; and - 0.01 score; 95%CI: -0.03; 0.03, at 12-wk and 24-wk respectively) and total PA (-0.02 score; 95%CI: -0.2; 0.2; and - 0.01score; 95%CI: -0.2; 0.2, at 12 and 24 weeks respectively). After 24 weeks, we observed a significant group by time effects for lower body muscular fitness (12.9 cm; 95%CI, 3.2 to 22.2). CONCLUSION: The implementation of aerobic and muscle-strengthening exercises used in the ActTeens intervention did not lead to improvements in physical activity. The intervention resulted in improved lower body muscular fitness, however, we found no significant differences for upper body muscular and cardiorespiratory fitness.


Assuntos
Exercício Físico , Educação Física e Treinamento , Aptidão Física , Humanos , Feminino , Masculino , Adolescente , Exercício Físico/fisiologia , Brasil , Educação Física e Treinamento/métodos , Aptidão Cardiorrespiratória/fisiologia , Serviços de Saúde Escolar , Promoção da Saúde/métodos , Avaliação de Programas e Projetos de Saúde , Estilo de Vida Saudável
8.
Parasitol Res ; 123(2): 143, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407619

RESUMO

The objective of the study was to evaluate the in vitro and in vivo schistosomicidal activity of sanguinarine (SA) on Schistosoma mansoni and its in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The activity of SA in vitro, at the concentrations of 1.0-25 µM, was analyzed through the parameters of motility, mortality, and cell viability of the worms at intervals of 3-24 h. Mice were infected with cercariae and treated by gavage with SA (5 mg/kg/day, in a single dose or two doses of 2.5 mg/kg every 12 h for 5 consecutive days) on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms), and 45th (adult worms) days after infection. In vitro and in vivo praziquantel was the control. In vitro, SA showed schistosomicidal activity against schistosomula, young worms, and couples; with total mortality and reduced cell viability at low concentrations and incubation time. In a single dose of 5 mg/kg/day, SA reduces the total worm load by 47.6%, 54%, 55.2%, and 27.1%, and female worms at 52.0%, 39.1%, 52.7%, and 20.2%, respectively, results which are similar to the 2.5 mg/kg/day dose. SA reduced the load of eggs in the liver, and in histopathological and histomorphometric analyses, there was a reduction in the number and volume of hepatic granulomas, which exhibited less inflammatory infiltrate. SA has promising in vitro and in vivo schistosomicidal activity against different developmental stages of S. mansoni, in addition to reducing granulomatous liver lesions. Furthermore, in silico, SA showed good predictive pharmacokinetic ADMET profiles.


Assuntos
Alcaloides , Anti-Infecciosos , Isoquinolinas , Esquistossomicidas , Feminino , Animais , Camundongos , Antiparasitários , Schistosoma mansoni , Benzofenantridinas/farmacologia , Alcaloides/farmacologia
9.
Chem Biodivers ; 21(8): e202400072, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38780224

RESUMO

The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.


Assuntos
Antipiréticos , Antitussígenos , Etanol , Expectorantes , Momordica charantia , Extratos Vegetais , Folhas de Planta , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Camundongos , Antitussígenos/farmacologia , Antitussígenos/química , Antitussígenos/isolamento & purificação , Folhas de Planta/química , Ratos , Etanol/química , Antipiréticos/farmacologia , Antipiréticos/química , Antipiréticos/isolamento & purificação , Masculino , Momordica charantia/química , Expectorantes/farmacologia , Expectorantes/isolamento & purificação , Expectorantes/química , Tosse/tratamento farmacológico , Ratos Wistar , Relação Dose-Resposta a Droga , Saccharomyces cerevisiae/efeitos dos fármacos , Febre/tratamento farmacológico
10.
Bioprocess Biosyst Eng ; 47(9): 1533-1545, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38888622

RESUMO

Rhodococcus erythropolis bacterium is known for its remarkable resistance characteristics that can be useful in several biotechnological processes, such as bioremediation. However, there is scarce knowledge concerning the behavior of this strain against different metals. This study sought to investigate the behavior of R. erythropolis ATCC 4277 against the residue of chalcopyrite and e-waste to verify both resistive capacities to the metals present in these residues and their potential use for biomining processes. These tests were carried out in a stirred tank bioreactor for 48 h, at 24ºC, pH 7.0, using a total volume of 2.0 L containing 2.5% (v/v) of a bacterial pre-culture. The pulp density of chalcopyrite was 5% (w/w), and agitation and oxygen flow rates were set to 250 rpm and 1.5 LO2 min-1, respectively. On the other hand, we utilized a waste of computer printed circuit board (WPCB) with a pulp density of 10% (w/w), agitation at 400 rpm, and an oxygen flow rate of 3.0 LO2 min-1. Metal concentration analyses post-fermentation showed that R. erythropolis ATCC 4277 was able to leach about 38% of the Cu present in the chalcopyrite residue (in ~ 24 h), and 49.5% of Fe, 42.3% of Ni, 27.4% of Al, and 15% Cu present in WPCB (in ~ 24 h). In addition, the strain survived well in the environment containing such metals, demonstrating the potential of using this bacterium for waste biomining processes as well as in other processes with these metals.


Assuntos
Reatores Biológicos , Rhodococcus , Rhodococcus/metabolismo , Rhodococcus/crescimento & desenvolvimento , Cobre/química , Metais/química , Biodegradação Ambiental , Resíduo Eletrônico
11.
J Prosthet Dent ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38307751

RESUMO

STATEMENT OF PROBLEM: Disinfection is an important factor in preserving facial prostheses and maintaining tissue health. However, whether disinfection with ultraviolet C is an effective disinfection method is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effectiveness of irradiation with different exposure durations of an ultraviolet-C light-emitting diode in the disinfection of the silicone (A-588-1; Factor II) used in facial prostheses. MATERIAL AND METHODS: A total of 216 specimens were prepared, contaminated by multispecies biofilm, and divided into 9 groups (n=24) for different treatments: chlorhexidine 0.12% (G CHG), ultraviolet-C light-emitting diode for 5 minutes (G UVC5), ultraviolet-C light-emitting diode for 10 minutes (G UVC10), ultraviolet-C light-emitting diode for 20 minutes (G UVC20), their respective untreated controls (Gcontrol CHG, Gcontrol UVC5, Gcontrol UVC10, Gcontrol UVC20), and dimethyl sulfoxide (G DMSO) as the negative control. Cell viability was measured by using the methyl tetrazolium salt (MTT) method. Two statistical analyses were performed. First, a 2×3 ANOVA was carried out to compare the control groups (Gcontrol UVC5, Gcontrol UVC10, and Gcontrol UVC20) and the experimental groups of UV-C LED light with different exposure durations (G UVC5, G UVC10, and G UVC20). The second analysis was performed using generalized linear models to compare the optical density of the groups (G UVC5, G UVC10, G UVC20, G CHG, and G DMSO). RESULTS: Cell viability results demonstrated a microbial reduction after exposure to the ultraviolet-C light-emitting diode for 20 minutes (G UVC20) compared with untreated controls (P<.05). The 5- and 10-minute exposures were statistically similar to their respective control groups (P>.05). The 20 minutes exposure had the lowest average optical density value, being statistically different from the 5-minute exposure (P<.05). A 20-minute exposure to the ultraviolet-C light-emitting diode (G UVC20) was similarly effective when compared with the standard disinfection treatment (G CHG) and dimethyl sulfoxide (G DMSO) (P>.05). CONCLUSIONS: Irradiation with an ultraviolet-C light-emitting diode for 20 minutes decreased the in vitro microbial cell viability on the medical silicone used in facial prostheses.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39087887

RESUMO

Artemia is a brine shrimp genus adapted to extreme habitats like ranges salinity from 5-25 g/L and in temperatures from 9 to 35 °C. It is widely distributed and used as an environmental quality biomarker. Artemia franciscana and Artemia salina species are commonly used in ecotoxicological studies and genotoxicity assays due to their short life cycle, high fecundity rate, easy culture, and availability. Thus, considering the importance of these tests in ecotoxicological studies, the present study aimed to present Artemia genus as a biological model in genotoxicity research. To this end, we reviewed the literature, analyzing data published until July 2023 in the Web of Science, SCOPUS, Embase, and PubMed databases. After screening, we selected 34 studies in which the genotoxicity of Artemia for various substances. This review presents the variability of the experimental planning of assays and biomarkers in genotoxicity using Artemia genus as a biological model for ecotoxicological studies and show the possibility of monitoring biochemical alterations and genetic damage effects. Also highlight innovative technologies such as transcriptomic and metabolomic analysis, as well as studies over successive generations to identify changes in DNA and consequently in gene expression.


Assuntos
Artemia , Ecotoxicologia , Testes de Mutagenicidade , Artemia/efeitos dos fármacos , Animais , Dano ao DNA , Poluentes Químicos da Água/toxicidade , Mutagênicos/toxicidade
13.
J Vasc Bras ; 23: e20230159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099702

RESUMO

Low-intensity laser therapy (LILT) is commonly used as an adjuvant therapy for treating injuries. This integrative literature review was carried out in the MEDLINE, LILACS, CUMED, BDENF, SPORTDiscus, Dentistry & Oral Sciences Source, Academic Source and CINAHL databases. Among the inclusion criteria were: range from 2011 to 2021, in English, Portuguese and Spanish and any study, with the exception of preprints and books. The question was answered: "What is the effectiveness described in the literature of using low-intensity laser therapy (LILT) in the treatment of venous lesions?" The wavelength used in studies varied from 635 nm of red ray to 780 nm of infrared ray, generating healing improvement at any length. LBI presented itself as a low-cost and easy-to-apply adjuvant option, alleviating pain complaints and improving healing in patients with vasculogenic lesions.

14.
Eur J Orthop Surg Traumatol ; 34(3): 1717-1729, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38236398

RESUMO

The aim of the present study was to summarize the effectiveness of amino acid supplementation on muscle strength, muscle volume, and functional capacity in patients undergoing total knee arthroplasty. For this, in November 2022, a search was carried out in the PubMed, Cochrane Library, and EMBASE databases, identifying a total of 2182 documents, of which only 4 were included in the present review. The included studies had 148 participants (47 men and 101 women), with a minimum age of 53 and a maximum of 92 years, and supplementation times of 13 to 30 days (1 to 3 times a day). For the results, in relation to muscle performance, when comparing the control and experimental groups, greater muscle atrophy was observed in the pre- and post-moments of the control group, in relation to the experimental group. In addition, studies suggest a good tendency for muscle mass gain, and improvement in the functional capacities of patients who used supplementation. Therefore, the use of amino acids after TKA surgery reduces muscle atrophy, which preserves muscle mass and leads to better performance in tests of strength and functional capacity, when compared to the use of a placebo.


Assuntos
Aminoácidos , Artroplastia do Joelho , Suplementos Nutricionais , Força Muscular , Músculo Esquelético , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Humanos , Masculino , Aminoácidos/administração & dosagem , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Músculo Esquelético/fisiopatologia , Atrofia Muscular/prevenção & controle , Atrofia Muscular/etiologia
15.
Am J Physiol Cell Physiol ; 324(3): C741-C756, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745527

RESUMO

Vasoactive peptides often serve a multitude of functions aside from their direct effects on vasodynamics. This article will review the existing literature on two vasoactive peptides and their involvement in skin homeostasis: adiponectin and-as the main representative of the kallikrein-kinin system-bradykinin. Adiponectin is the most abundantly expressed adipokine in the human organism, where it is mainly localized in fat depots including subcutaneous adipose tissue, from where adiponectin can exert paracrine effects. The involvement of adiponectin in skin homeostasis is supported by a number of studies reporting the effects of adiponectin in isolated human keratinocytes, sebocytes, fibroblasts, melanocytes, and immune cells. Regarding skin pathology, the potential involvement of adiponectin in psoriasis, atopic dermatitis, scleroderma, keloid, and melanogenesis is discussed in this article. The kallikrein-kinin system is composed of a variety of enzymes and peptides, most of which have been identified to be expressed in the skin. This also includes the expression of bradykinin receptors on most skin cells. Bradykinin is one of the very few hormones that is targeted by treatment in routine clinical use in dermatology-in this case for the treatment of hereditary angioedema. The potential involvement of bradykinin in wound healing, psoriasis, and melanoma is further discussed in this article. This review concludes with a call for additional preclinical and clinical studies to further explore the therapeutic potential of adiponectin supplementation (for psoriasis, atopic dermatitis, wound healing, scleroderma, and keloid) or pharmacological interference with the kallikrein-kinin system (for wound healing, psoriasis, and melanoma).


Assuntos
Adiponectina , Bradicinina , Homeostase , Sistema Calicreína-Cinina , Dermatopatias , Fenômenos Fisiológicos da Pele , Adiponectina/fisiologia , Sistema Calicreína-Cinina/fisiologia , Bradicinina/fisiologia , Humanos , Dermatopatias/metabolismo
16.
Clin Immunol ; 251: 109331, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37088297

RESUMO

CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.


Assuntos
Antineoplásicos , Cardiomiopatia Chagásica , Doença de Chagas , Trypanosoma cruzi , Humanos , Linfócitos T CD8-Positivos/metabolismo , Trypanosoma cruzi/metabolismo , Citocinas/metabolismo
17.
Microb Ecol ; 86(4): 2847-2857, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37606696

RESUMO

Moonmilk is a cave deposit that was used for medical and cosmetic purposes and has lately raised interest for its antimicrobial potential. We studied five moonmilk samples from four caves with different microclimatic conditions, two temperate in north-western and northern Romania (Ferice, Fața Apei, and Izvorul Taușoarelor caves) and one tropical in Minas Gerais, Brazil (Nestor Cave). The physicochemical and mineralogical analyses confirmed the presence of calcite and dolomite as the main phase in the moonmilk. A 16S rRNA gene-based metabarcoding approach showed the most abundant bacteria phyla Proteobacteria, GAL15, Actinobacteriota, and Acidobacteriota. The investigated caves differed in the dominant orders of bacteria, with the highest distance between the Romanian and Nestor Cave samples. Climate and, implicitly, the soil microbiome can be responsible for some differences we found between all the samples. However, other factors can be involved in shaping the moonmilk microbiome, as differences were found between samples in the same cave (Ferice). In our five moonmilk samples, 1 phylum, 70 orders (~ 36%), and 252 genera (~ 47%) were unclassified, which hints at the great potential of cave microorganisms for future uses.


Assuntos
Cavernas , Microbiota , Cavernas/microbiologia , RNA Ribossômico 16S/genética , Bactérias/genética , Proteobactérias/genética
18.
Exp Parasitol ; 250: 108547, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37196701

RESUMO

The current scenario for cutaneous leishmaniasis treatment includes the use of first and second-choice drugs, both therapeutic strategies presenting several adverse effects and being related to an increment of treatment-refractory parasite strains. These facts encourage the search for new treatment approaches, including repositioning drugs, such as nystatin. Although in vitro assays show that this polyene macrolide compound has leishmanicidal activity, no in vivo evidence for a similar activity has been shown so far for the commercial nystatin cream formulation. This work assessed the effects of nystatin cream (25,000 IU/g) administered on mice in an amount to completely cover the paw surface of BALB/c mice infected with Leishmania (L.) amazonensis once a day, until a total of up to 20 doses. The data presented herein points to unequivocal evidence that treatment with this formulation causes a statistically significant reduction of swelling/edema in mice paws when compared to animal groups not submitted to this treatment regimen after the fourth week of infection: lesion sizes at the sixth (p = 0.0159), seventh (p = 0.0079) and eighth (p = 0.0079) week. Furthermore, swelling/edema reduction relates to a decrease in parasite load in the footpad (∼48%) and in draining lymph nodes (∼68%) at eight weeks post-infection. This is the first report of the effectiveness of nystatin cream used as a topical treatment in BALB/c model for cutaneous leishmaniasis.


Assuntos
Leishmania , Leishmaniose Cutânea , Animais , Camundongos , Nistatina/farmacologia , Nistatina/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Resultado do Tratamento , Edema , Camundongos Endogâmicos BALB C
19.
J Cardiovasc Nurs ; 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37955376

RESUMO

BACKGROUND: Heart failure may cause peripheral and respiratory muscle alterations, dyspnea, fatigue, and exercise intolerance, worsening the quality of life of patients. OBJECTIVES: The aims of this study were to analyze respiratory muscle strength and quality of life of patients with heart failure and correlate them with clinical variables and functional classification. METHODS: This cross-sectional study involved patients with heart failure. A manovacuometer assessed maximum inspiratory and expiratory pressures, and quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire. Functional classification was categorized according to the New York Heart Association (NYHA) class in I, II, III, or IV. RESULTS: We included 60 patients (66.7% male) with a mean age of 62.0 years and mean left ventricular ejection fraction of 42.0%. Maximum inspiratory pressure and maximum expiratory pressure were close to normal (>70% of predicted) in most patients; however, a subgroup composed mostly of patients with dilated heart failure and NYHA class III (n = 21) presented low maximum inspiratory pressure values (59.2%; 95% confidence interval, 55.7%-62.8%). The mean total score of the Minnesota Living with Heart Failure Questionnaire was 44.4 points, being negatively correlated with left ventricular ejection fraction (r = -0.29, P = .02). Patients with NYHA class III and disease duration longer than 120 months presented higher total (P < .01) and physical dimension scores. CONCLUSIONS: Most patients had respiratory muscle strength close to normal; however, those with dilated heart failure and NYHA class III presented low maximum inspiratory pressure values. Quality of life was moderately compromised, mainly because of long disease duration, NYHA class III, and low left ventricular ejection fraction.

20.
J Environ Manage ; 338: 117804, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36996570

RESUMO

The bacterial synthesis of copper nanoparticles emerges as an eco-friendly alternative to conventional techniques since it comprises a single-step and bottom-up approach, which leads to stable metal nanoparticles. In this paper, we studied the biosynthesis of Cu-based nanoparticles by Rhodococcus erythropolis ATCC4277 using a pre-processed mining tailing as a precursor. The influence of pulp density and stirring rate on particle size was evaluated using a factor-at-time experimental design. The experiments were carried out in a stirred tank bioreactor for 24 h at 25 °C, wherein 5% (v/v) of bacterial inoculum was employed. The O2 flow rate was maintained at 1.0 L min-1 and the pH at 7.0. Copper nanoparticles (CuNPs), with an average hydrodynamic diameter of 21 ± 1 nm, were synthesized using 25 g.L-1 of mining tailing and a stirring rate of 250 rpm. Aiming to visualize some possible biomedical applications of the as-synthesized CuNPs, their antibacterial activity was evaluated against Escherichia coli and their cytotoxicity was evaluated against Murine Embryonic Fibroblast (MEF) cells. The 7-day extract of CuNPs at 0.1 mg mL-1 resulted in 75% of MEF cell viability. In the direct method, the suspension of CuNPs at 0.1 mg mL-1 resulted in 70% of MEF cell viability. Moreover, the CuNPs at 0.1 mg mL-1 inhibited 60% of E. coli growth. Furthermore, the NPs were evaluated regarding their photocatalytic activity by monitoring the oxidation of methylene blue (MB) dye. The CuNPs synthesized showed rapid oxidation of MB dye, with the degradation of approximately 65% of dye content in 4 h. These results show that the biosynthesis of CuNPs by R. erythropolis using pre-processed mine tailing can be a suitable method to obtain CuNPs from environmental and economical perspectives, resulting in NPs useful for biomedical and photocatalytic applications.


Assuntos
Proteínas de Escherichia coli , Nanopartículas Metálicas , Camundongos , Animais , Cobre/química , Escherichia coli , Nanopartículas Metálicas/química , Bactérias , Oxirredução , Antibacterianos/química , Proteínas de Ciclo Celular
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