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1.
Nat Immunol ; 25(7): 1158-1171, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38902519

RESUMO

Up to 25% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit postacute cognitive sequelae. Although millions of cases of coronavirus disease 2019 (COVID-19)-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1 (IL-1), a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of individuals with COVID-19. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 Beta variant leads to central nervous system infiltration of Ly6Chi monocytes and microglial activation. Accordingly, SARS-CoV-2, but not H1N1 influenza virus, increases levels of brain IL-1ß and induces persistent IL-1R1-mediated loss of hippocampal neurogenesis, which promotes postacute cognitive deficits. Vaccination with a low dose of adenoviral-vectored spike protein prevents hippocampal production of IL-1ß during breakthrough SARS-CoV-2 infection, loss of neurogenesis and subsequent memory deficits. Our study identifies IL-1ß as one potential mechanism driving SARS-CoV-2-induced cognitive impairment in a new mouse model that is prevented by vaccination.


Assuntos
COVID-19 , Hipocampo , Interleucina-1beta , Transtornos da Memória , Camundongos Endogâmicos C57BL , Neurogênese , SARS-CoV-2 , Animais , Interleucina-1beta/metabolismo , Interleucina-1beta/imunologia , Camundongos , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Hipocampo/imunologia , Hipocampo/metabolismo , Transtornos da Memória/imunologia , Neurogênese/imunologia , Vacinação , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas contra COVID-19/imunologia , Masculino , Humanos , Microglia/imunologia , Microglia/metabolismo , Modelos Animais de Doenças , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1/genética , Monócitos/imunologia , Monócitos/metabolismo , Feminino
2.
J Neuroinflammation ; 21(1): 24, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233868

RESUMO

BACKGROUND: Venezuelan Equine Encephalitis virus (VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after intranasal exposure. While it is known that VEEV has evolved several mechanisms to inhibit type I interferon (IFN) signaling within infected cells, whether this inhibits virologic control during neuroinvasion along OSN has not been studied. METHODS: We utilized an established murine model of intranasal infection with VEEV and a repository of scRNAseq data from IFN-treated OSN to assess the cellular targets and IFN signaling responses after VEEV exposure. RESULTS: We found that immature OSN, which express higher levels of the VEEV receptor LDLRAD3 than mature OSN, are the first cells infected by VEEV. Despite rapid VEEV neuroinvasion after intranasal exposure, olfactory neuroepithelium (ONE) and olfactory bulb (OB) IFN responses, as assessed by evaluation of expression of interferon signaling genes (ISG), are delayed for up to 48 h during VEEV neuroinvasion, representing a potential therapeutic window. Indeed, a single intranasal dose of recombinant IFNα triggers early ISG expression in both the nasal cavity and OB. When administered at the time of or early after infection, IFNα treatment delayed onset of sequelae associated with encephalitis and extended survival by several days. VEEV replication after IFN treatment was also transiently suppressed in the ONE, which inhibited subsequent invasion into the CNS. CONCLUSIONS: Our results demonstrate a critical and promising first evaluation of intranasal IFNα for the treatment of human encephalitic alphavirus exposures.


Assuntos
Vírus da Encefalite Equina Venezuelana , Neurônios Receptores Olfatórios , Humanos , Camundongos , Animais , Vírus da Encefalite Equina Venezuelana/genética , Sistema Nervoso Central , Replicação Viral
3.
Artigo em Inglês | MEDLINE | ID: mdl-38870494

RESUMO

Objectives: This study aimed to explore the experiences and caregiving perspectives of mothers from low-income families who have children with asthma,and to establish a foundation for the development of tailored nursing strategies specifically designed for families facing similar circumstances. Method: A descriptive qualitative research method was employed. Fifteen mothers of asthmatic children from low-income families receiving treatment at the Respiratory Centre of Chongqing Children's Hospital were purposefully sampled from June to December 2021. Semi-structured interviews were conducted to gather data on their caregiving experiences, and thematic analysis was utilized to analyze the interview data. Results: The interviewees were 27-42 years old (SD=32.3 years), 33.3% were full-time mothers(A woman who quit work, in order to focus on taking care of the child and the family ), 53.3% had one child, 46.6% had a college degree or higher, and 100% had health insurance. Through in-depth interviews, four main themes and eight sub-themes were identified, including (a) insufficient knowledge about the disease, (b) anxiety and uncertainty, (c) insufficient social support system, and (d) insufficient resources for medical services. The first theme describes a weak willingness to learn and medication discontinuation at will. The second theme describes financial burden and psychological stress, the third theme describes lack of family support and low social participation, and the fourth theme describes insufficient health insurance support and unequal distribution of healthcare resources. Conclusion: Mothers from low-income families with asthmatic children face substantial psychological burdens and familial pressures. It is crucial for healthcare professionals to actively engage with and deepen their understanding of these mothers' caregiving experiences and psychological well-being. By doing so, positive coping strategies can be developed, promoting the physical and mental health of these mothers and improving asthma control in their children.

4.
Sci Rep ; 14(1): 14301, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906965

RESUMO

A substantial body of empirical evidence reveals that physical activity is associated with a wide range of positive physical and mental health outcomes. However, an absence of comprehensive syntheses is observed concerning the varying effects of different exercise intensities on the improvement of physical health among children and adolescents. The aim of this review is to systematically investigate the effects of different exercise intensities on the physical fitness of children and adolescents, to analyses the optimal exercise intensities for improving physical fitness, and to provide a relevant theoretical basis for optimizing school physical education curricula. A systematic search strategy was used in this study in four online databases (PubMed, Scopus, EBSCO and Web of Science). Intervention studies that met the inclusion criteria underwent a thorough screening process, and their methodological quality was assessed utilizing the PEDro scale. The selected literature was systematically analyzed and evaluated through induction, summary, analysis, and evaluation. These findings indicate that high-intensity exercise training exerts significant positive effects on body composition, cardiopulmonary function and muscle fitness in children and adolescents. Therefore, we suggest that schools should focus on high-intensity sports in their physical education curriculum, which can further improve the student's PHYSICAL FITNESS.


Assuntos
Exercício Físico , Aptidão Física , Humanos , Adolescente , Criança , Aptidão Física/fisiologia , Exercício Físico/fisiologia , Masculino , Feminino , Composição Corporal , Educação Física e Treinamento/métodos
5.
J Affect Disord ; 354: 275-285, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38490590

RESUMO

FOR FULL-LENGTH ARTICLES: This study systematically identified the effects of physical activity (PA) on depression, anxiety and weight-related outcomes among children and adolescents with overweight/obesity. EMBASE, The Cochrane Library, Web of Science, and PubMed were searched from January 1, 2000 to August 1, 2022 for peer-reviewed papers. Meta-analyses were conducted to ascertain the effect of physical activity on symptoms of anxiety, depression and weight-related outcomes in overweight/obese children and adolescents. Twenty-five studies representing 2188 participants, with median age 12.08 years old (8.3 to 18.44 years) were included. Depressive and anxiety symptoms, BMI, BMI z-scores, weight, waist circumference and height were evaluated. After incorporating the effects of PA interventions on children and adolescents with overweight/obesity, PA could improve depressive and anxiety symptoms, but not obesity indexes except waist circumference. While, PA combined with other interventions have a significant effect both on anxiety symptoms and BMI compared to pure PA intervention. In terms of intervention duration, we observed that durations falling within the range of 8 to 24 weeks exhibited the most positive effects on reducing depressive symptoms. FOR SHORT COMMUNICATIONS: We included 25 articles on the effects of physical activity on psychological states such as depression and anxiety, weight, BMI and other weight-related indicators in children and adolescents with overweight/obesity. We attempted to determine the most appropriate type of physical activity intervention for children and adolescents with overweight/obesity, as well as the most appropriate population characteristics and duration by combining the outcome data from each article. This has a great enlightening effect for health workers to carry out corresponding strategies in the future.


Assuntos
Ansiedade , Índice de Massa Corporal , Depressão , Exercício Físico , Obesidade Infantil , Humanos , Adolescente , Criança , Obesidade Infantil/psicologia , Obesidade Infantil/terapia , Depressão/psicologia , Ansiedade/psicologia , Masculino , Feminino
6.
Small Methods ; : e2400249, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634403

RESUMO

Aqueous zinc-ion batteries (AZIBs) directly using zinc metal anodes are promising candidates for grid-scale energy storage systems due to their intrinsic high theoretical capacity, high safety, and environmental friendliness. However, the uncontrolled dendrite growth and water-triggered side reactions seriously plague its practical application. Herein, a cost-effective and green additive, maltodextrin (MD) is presented, to simultaneously guide the smooth Zn deposition and inhibit the occurrence of water-related side reactions. Combing experimental characterizations and theoretical calculations shows that the MD molecules could reconstruct the Helmholtz plane, induces a preferential growth of zinc along the (002) plane, and the optimized regulation of the Zn2+ diffusion path and deposition location also results in the formation of fine-grained Zn deposition layers, thereby inhibiting dendrite growth. In addition, MD molecules readily adsorb to the zinc anode surface, which isolates water molecules from direct contact with the zinc metal, reducing hydrogen precipitation reactions and inhibiting the formation of by-products. Consequently, the Zn||Zn symmetric cell with MD achieves ultra-long stable cycles of up to 5430 h at 1 mA cm-2 and 1 mA h cm-2, and the Cu||Zn asymmetric cell can stable cycle 1000 cycles with an average coulomb efficiency of 99.78%.

7.
Biol. Res ; 50: 26, 2017. graf
Artigo em Inglês | LILACS | ID: biblio-950876

RESUMO

BACKGROUND: CCL2 was up-regulated in neurons and involved in microglia activation and neurological decline in mice suffering from hepatic encephalopathy (HE). However, no data exist concerning the effect of neuron-derived CCL2 on microglia activation in vitro. METHODS: The rats were pretreated with CCL2 receptor inhibitors (INCB or C021, 1 mg/kg/day i.p.) for 3 days prior to thioacetamide (TAA) administration (300 mg/kg/day i.p.) for inducing HE model. At 8 h following the last injection (and every 4 h after), the grade of encephalopathy was assessed. Blood and whole brains were collected at coma for measuring CCL2 and Iba1 expression. In vitro, primary neurons were stimulated with TNF-α, and then the medium were collected for addition to microglia cultures with or without INCB or C021 pretreatment. The effect of the medium on microglia proliferation and activation was evaluated after 24 h. RESULTS: CCL2 expression and microglia activation were elevated in the cerebral cortex of rats received TAA alone. CCL2 receptors inhibition improved neurological score and reduced cortical microglia activation. In vitro, TNF-α treatment induced CCL2 release by neurons. Medium from TNF-α stimulated neurons caused microglia proliferation and M1 markers expression, including iNOS, COX2, IL-6 and IL-1ß, which could be suppressed by INCB or C021 pretreatment. The medium could also facilitate p65 nuclear translocation and IκBα phosphorylation, and NF-κB inhibition reduced the increased IL-6 and IL-1ß expression induced by the medium. CONCLUSION: Neuron-derived CCL2 contributed to microglia activation and neurological decline in HE. Blocking CCL2 or inhibiting microglia excessive activation may be potential strategies for HE.


Assuntos
Animais , Ratos , Encefalopatia Hepática/metabolismo , Microglia/metabolismo , Quimiocina CCL2/metabolismo , Receptores de Quimiocinas/antagonistas & inibidores , Neurônios/metabolismo , Tioacetamida , Expressão Gênica , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/terapia , Interleucina-6/metabolismo , Microglia/efeitos dos fármacos , Quimiocina CCL2/antagonistas & inibidores , Meios de Cultura/farmacologia , Modelos Animais de Doenças , Doenças do Sistema Nervoso
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