RESUMO
Vascular cognitive impairment (VCI) encompasses a range of cognitive deficits arising from vascular pathology. The pathophysiological mechanisms underlying VCI remain incompletely understood; however, chronic cerebral hypoperfusion (CCH) is widely acknowledged as a principal pathological contributor. Mitochondria, crucial for cellular energy production and intracellular signaling, can lead to numerous neurological impairments when dysfunctional. Recent evidence indicates that mitochondrial dysfunction-marked by oxidative stress, disturbed calcium homeostasis, compromised mitophagy, and anomalies in mitochondrial dynamics-plays a pivotal role in VCI pathogenesis. This review offers a detailed examination of the latest insights into mitochondrial dysfunction within the VCI context, focusing on both the origins and consequences of compromised mitochondrial health. It aims to lay a robust scientific groundwork for guiding the development and refinement of mitochondrial-targeted interventions for VCI.
Assuntos
Disfunção Cognitiva , Mitocôndrias , Estresse Oxidativo , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/metabolismo , Animais , Estresse Oxidativo/fisiologia , Mitofagia , Demência Vascular/fisiopatologia , Demência Vascular/metabolismo , Demência Vascular/patologia , Dinâmica Mitocondrial , Cálcio/metabolismoRESUMO
The exacerbation of pneumonia in children with human adenovirus type 3 (HAdV-3E) is secondary to a Staphylococcus aureus (S. aureus) infection. The influence of host-pathogen interactions on disease progression remains unclear. It is important to note that S. aureus infections following an HAdV-3E infection are frequently observed in clinical settings, yet the underlying susceptibility mechanisms are not fully understood. This study utilized an A549 cell model to investigate secondary infection with S. aureus following an HAdV-3E infection. The findings suggest that HAdV-3E exacerbates the S. aureus infection by intensifying lung epithelial cell damage. The results highlight the role of HAdV-3E in enhancing the interferon signaling pathway through RIG-I (DDX58), resulting in the increased expression of interferon-stimulating factors like MX1, RSAD2, and USP18. The increase in interferon-stimulating factors inhibits the NF-κB and MAPK/P38 pro-inflammatory signaling pathways. These findings reveal new mechanisms of action for HAdV-3E and S. aureus in secondary infections, enhancing our comprehension of pathogenesis.
Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Proteína DEAD-box 58 , Transdução de Sinais , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Infecções por Adenovirus Humanos/metabolismo , Infecções por Adenovirus Humanos/imunologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/fisiologia , Adenovírus Humanos/imunologia , Coinfecção/microbiologia , Proteína DEAD-box 58/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Inflamação/metabolismo , NF-kappa B/metabolismo , Receptores Imunológicos/metabolismo , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Ubiquitina TiolesteraseRESUMO
Metal-Organic Frameworks (MOFs) offer new ideas for the design of antibacterial materials because of their antibacterial properties, high porosity and specific surface area, low toxicity and good biocompatibility compared with other nanomaterials. Herein, a novel antimicrobial nanomaterial, MIL-101(Fe)@ZnO, has been synthesized by hydrothermal synthesis and characterized by FTIR, UV-vis, ICP-OES, XRD, SEM, EDS and BET to show that the zinc ions are doped into the crystal lattice of MIL-101(Fe) to form a Fe-Zn bimetallic structure. MIL-101(Fe)@ZnO was found to be effective against a wide range of antibacterial materials including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Acinetobacter junii and Staphylococcus epidermidis. It has a significant antibacterial effect, weak cytotoxicity, high safety performance and good biocompatibility. Meanwhile, MIL-101(Fe)@ZnO was able to achieve antibacterial effects by causing cells to produce ROS, disrupting the cell membrane structure, and causing protein leakage and lipid preoxidation mechanisms. In conclusion, MIL-101(Fe)@ZnO is an easy-to-prepare antimicrobial nanomaterial with broad-spectrum bactericidal activity and low toxicity.
Assuntos
Estruturas Metalorgânicas , Nanopartículas , Óxido de Zinco , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Estruturas Metalorgânicas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Ferroptosis is an important form of myocardial cell death in myocardial ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has a significant advantage in improving MIRI. But the regulatory effect and mechanism of NAR on ferroptosis in MIRI have not been reported. After the rats were given NAR and induced to form myocardial ischemia-reperfusion (MI/R) injury, Tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats, and Hematoxylin-eosin (H&E) staining was used to detect myocardial injury. The markers of tissue inflammation were detected by ELISA. Serum creatine kinase Serum creatin kinase (CPK), Lactate dehydrogenase (LDH), and lipid peroxide (LPO) and oxidative stress related levels were measured. In addition, iron detection kits were used to detect total iron and Fe2+ levels in cardiac tissues, and western blot was used to detect the expression of ferroptosis-related proteins and the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). At the cellular level, H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and ferroptosis inducer Erastin was administered to detect cell viability, ferroptosis-related indicators, oxidative stress related indicators, and expressions of Nrf2 and GPX4, to explore the mechanisms involved. NAR alleviated MI/R-induced pathological damage, inflammation and lipid peroxidation in myocardial tissue of rats. NAR adjusted the NRF2 /System xc - /GPX4 axis and improved ferroptosis. At the cellular level, ferroptosis inducer Erastin reversed the protective effect of NAR on H/R-induced H9C2 cardiomyocytes. In conclusion, NAR can alleviate MIRI by regulating the Nrf2/System xc-/GPX4 axis to inhibit ferroptosis.
Assuntos
Ferroptose/efeitos dos fármacos , Flavanonas/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
INTRODUCTION: Takotsubo syndrome (TTS) is a sudden reversible weakening of the left ventricle function induced by severe stress and resembles many features as acute coronary syndrome. Even though many guidelines had been published about TTS, there is no consensus regarding the long-term treatment. Aspirin is one of the most common prescribed medicines at discharge for patients with the intention to reduce thrombus events and improve the overall prognosis. However, existing studies yielded conflicting results concerning its effects. This study aims to evaluate the impact of long-term maintenance treatment of aspirin in TTS and provides insights in clinical management. METHODS AND ANALYSIS: After searching through electronic databases (PubMed, Embase, Cochrane Library, Web of Science, National Library of Medicine Gateway, CNKI, Wanfang and VIP), grey literatures, conference abstract and trial registries for clinical studies investigating the impact of aspirin on patients with TTS, a systemic review and meta-analysis will be conducted. The search will be limited from inception of each database to 1 August 2020. The outcomes including all-cause death, TTS recurrence, stroke, transient ischaemic attack or myocardial infarction at 30-day and 5-year follow-up will be examined. Risk of bias will be assessed by Newcastle-Ottawa quality assessment scale for observational studies and Cochrane Effective Practice and Organization of Care evaluation tool for interventional studies. Grading of Recommendations Assessment, Development and Evaluations method will be applied to assess the quality of evidence. If available, the effects of aspirin on the above outcomes for patients with TTS will be evaluated using random-effect modelling with relative risk at 95% CIs. Subgroup analysis and sensitivity analysis will also be performed when possible. ETHICS AND DISSEMINATION: Ethics approval was not required due to the retrospective nature of the study. Results of the review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020212729.
Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Cardiomiopatia de Takotsubo , Aspirina/uso terapêutico , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Estudos Retrospectivos , Revisões Sistemáticas como AssuntoRESUMO
Objectives: Although Baduanjin (a traditional Chinese physical activity) has been reported to promote general health, the optimal exercise intensity and kinematic characteristics of this intervention remain poorly understood. This investigation aimed to quantify and compare the exercise intensities of traditional standing Baduanjin (TB) and sitting Baduanjin (SB) using cardiopulmonary exercise testing, to further clarify the sources of the previously observed benefits of this modality. Study design: Observational study. Interventions: Healthy individuals were recruited to perform TB, SB, and cycling (in order) until they reached their ventilatory threshold. Intensity-relevant parameters based on type of exercise and specific time points (exercise start and the end of the 2nd, 4th, 6th, and 8th set of motion) were compared between TB and SB with ventilatory threshold as control. Results: Forty individuals (18 male and 22 female) completed the trial. Significant differences in peak oxygen uptake, metabolic equivalent of task, and Borg scale existed among the three exercise types, indicating a decreasing overall exercise intensity in the order of ventilatory threshold, TB, and SB. All parameters except the respiratory exchange ratio fluctuated significantly across the time points. Conclusions: Both TB and SB resulted in a significantly lower exercise intensity when compared with the ventilatory threshold established through cycling exercise. The benefits of Baduanjin might be explained partly by its appropriate exercise intensity and intermittent intensity pattern. Baduanjin might be a potential alternative to existing schemes for exercise rehabilitation.
Assuntos
Exercício Físico , Postura Sentada , Terapia por Exercício , Feminino , Nível de Saúde , Humanos , MasculinoRESUMO
OBJECTIVE: To assess the efficacy of Tai Chi (TC) in patients with myocardial infarction and provide up-to-date evidence for its application. DATA SOURCES: Three English databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) and 3 Chinese databases (China Knowledge Resource Integrated, Wanfang, Weipu) were screened for the time period between January 1, 1976 and May 31, 2019. STUDY SELECTION: Seven randomized and controlled experiments were included. DATA EXTRACTION: Two independent researchers under 2 independent advisors extracted and classified the data from all relevant studies based on the prespecified inclusion criteria and rules for data extraction. DATA SYNTHESIS: A total of 615 patients were included in this study. The TC group was comprised of 294 patients, and the control group included 261 patients. The results revealed that TC has significant effects on the outcomes of the 6-minute walk (standardized mean difference, 1.30; 95% confidence interval, 0.50-2.11) and left ventricular ejection fraction (standardized mean difference, 1; 95% confidence interval, 0.43-1.57) compared with no or low-density exercise. Also, TC positively affected the quality of life, pro-B type natriuretic peptide, and short form-36. However, TC did not significantly affect activities of daily living (P=.060), sense of coherence-13 (P=.057) and N-terminal-pro-brain natriuretic peptide (P=.081). A moderate to high heterogeneity was observed across all comparisons. CONCLUSIONS: Compared with no exercise or other types of low-intensity physical activities, TC improved the outcome of the 6-minute walk, left ventricular ejection fraction, quality of life, and short form-36 scores, but reduced the outcome of pro-B type natriuretic peptide in patients with myocardial infarction. Therefore, TC could be an effective exercise option for cardiac rehabilitation. More research should be done to identify the effects of TC on academic functioning and to determine ways of motivating patients to use preventive TC interventions.