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Legionella is a common intracellular parasitic bacterium that infects humans via the respiratory tract, causing Legionnaires' disease, with fever and pneumonia as the main symptoms. The emergence of highly virulent and azithromycin-resistant Legionella pneumophila is a major challenge in clinical anti-infective therapy. The CRISPR-Cas acquired immune system provides immune defense against foreign nucleic acids and regulates strain biological functions. However, the distribution of the CRISPR-Cas system in Legionella and how it regulates gene expression in L. pneumophila remain unclear. Herein, we assessed 915 Legionella whole-genome sequences to determine the distribution characteristics of the CRISPR-Cas system and constructed gene deletion mutants to explore the regulation of the system based on growth ability in vitro, antibiotic sensitivity, and intracellular proliferation of L. pneumophila. The CRISPR-Cas system in Legionella was predominantly Type II-B and was mainly concentrated in the genome of L. pneumophila ST1 strains. The Type II-B CRISPR-Cas system showed no effect on the strain's growth ability in vitro but significantly reduced resistance to azithromycin and decreased proliferation ability due to regulation of the lpeAB efflux pump and the Dot/Icm type IV secretion system. Thus, the Type II-B CRISPR-Cas system plays a crucial role in regulating the virulence of L. pneumophila. This expands our understanding of drug resistance and pathogenicity in Legionella, provides a scientific basis for the prevention of Legionnaires' disease outbreaks and the rational use of clinical drugs, and facilitates effective treatment of Legionnaires' disease.
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Legionella pneumophila , Legionella , Doença dos Legionários , Humanos , Doença dos Legionários/microbiologia , Azitromicina/farmacologia , Sistemas CRISPR-Cas , Legionella pneumophila/genéticaRESUMO
PURPOSE: Duchenne muscular dystrophy (DMD) is currently the most commonly diagnosed form of muscular dystrophy due to mutations in the dystrophin gene. However, its pathological process remains unknown and there is a lack of specific molecular biomarkers. The aim of our study is to explore key regulatory connections underlying the progression of DMD. MATERIALS AND METHODS: The gene expression profile dataset GSE38417 of DMD was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between DMD patients and healthy controls were screened using geo2R, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. Then a protein-protein interaction (PPI) network and sub-network of modules were constructed. To investigate the regulatory network underlying DMD, a global triple network including miRNAs, mRNAs and transcription factors (TFs) was constructed. RESULTS: A total of 1811 DEGs were found between the DMD and control groups, among which HERC5, SKP2 and FBXW5 were defined as hub genes with a degree of connectivity >35 in the PPI network. Furthermore, the five TFs ZNF362, ATAT1, SPI1, TCF12 and ABCF2, as well as the eight miRNAs miR-124a, miR-200b/200c/429, miR-19a/b, miR-23a/b, miR-182, miR-144, miR-498 and miR-18a/b were identified as playing crucial roles in the molecular pathogenesis of DMD. CONCLUSIONS: This paper provides a comprehensive perspective on the miRNA-TF-mRNA co-regulatory network underlying DMD, although the bioinformatic findings need further validation in future studies.
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MicroRNAs , Distrofia Muscular de Duchenne , Biologia Computacional , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Distrofia Muscular de Duchenne/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: According to recent studies, the COVID-19 pandemic has been associated with an increased risk of mental health problems across many subpopulations including pregnant and postnatal women. This study examined the prevalence and correlates of depressive symptoms (depression hereafter) in Chinese pregnant and postpartum women during the COVID-19 pandemic. METHODS: This was a multicenter, cross-sectional study comprising 1309 pregnant and postpartum women across 12 provinces in China during the COVID-19 pandemic. Depression was assessed using the nine-item Patient Health Questionnaire. Univariate analyses and multivariate logistic regression analyses were conducted. RESULTS: The prevalence of depression in pregnant and postpartum women was 27.43% (95% confidence interval [CI] = 25.01%-29.85%). Women who were worried about themselves or their babies being infected with COVID-19 (odds ratio [OR] = 2.562, 95% CI = 1.670-3.929), and those who had delayed regular medical checkups (OR = 2.434, 95% CI = 1.580-3.750) were at higher risk of depression. Compared with those living in central and western parts of China, women living in northern (OR = 0.513, 95% CI = 0.326-0.807) and southeastern parts of China (OR = 0.626, 95% CI = 0.463-0.846) were less likely to have depression. CONCLUSIONS: The COVID-19 pandemic was associated with an increased likelihood of mental health problems among pregnant and postnatal women. Over a quarter of the pregnant and postpartum women in China had depression during the COVID-19 pandemic. Considering the negative health impact of depression, preventive measures, regular mental health screening, and medical checkups are needed with the goal to reduce the risk of depression in this vulnerable population during a pandemic.
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COVID-19/psicologia , Depressão Pós-Parto/epidemiologia , Depressão/epidemiologia , Complicações na Gravidez/psicologia , Adulto , COVID-19/complicações , China/epidemiologia , Estudos Transversais , Depressão/etiologia , Depressão Pós-Parto/etiologia , Feminino , Humanos , Modelos Logísticos , Pandemias/estatística & dados numéricos , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Prevalência , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: In the present study, we investigated the differentially expressed genes (DEGs), pathways and immune cell infiltration characteristics of pediatric and adult ulcerative colitis (UC). METHODS: We conducted DEG analysis using the microarray dataset GSE87473 containing 19 pediatric and 87 adult UC samples downloaded from the Gene Expression Omnibus. Gene ontology and pathway enrichment analyses were conducted using Metascape. We constructed the protein-protein interaction (PPI) network and the drug-target interaction network of DEGs and identified hub modules and genes using Cytoscape and analyzed immune cell infiltration in pediatric and adult UC using CIBERSORT. RESULTS: In total, 1700 DEGs were screened from the dataset. These genes were enriched mainly in inter-cellular items relating to cell junctions, cell adhesion, actin cytoskeleton and transmembrane receptor signaling pathways and intra-cellular items relating to the splicing, metabolism and localization of RNA. CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC were identified as hub DEGs. Immune cell infiltration analysis revealed higher proportions of naive B cells, resting memory T helper cells, regulatory T cells, monocytes, M0 macrophages and activated mast cells in pediatric UC, along with lower proportions of memory B cells, follicular helper T cells, γδ T cells, M2 macrophages, and activated dendritic cells. CONCLUSIONS: Our study suggested that hub genes CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC and immune cells including B cells, T cells, monocytes, macrophages and mast cells play vital roles in the pathological differences between pediatric and adult UC and may serve as potential biomarkers in the diagnosis and treatment of UC.
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Colite Ulcerativa , Biologia Computacional/métodos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Transdução de Sinais/genética , Adulto , Biomarcadores , Criança , Colite Ulcerativa/sangue , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Perfilação da Expressão Gênica/métodos , Humanos , Imunidade Celular/fisiologia , Comunicação Parácrina/fisiologiaRESUMO
BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in men. Alpha-blockers are widely used as first-line therapy for men with LUTS secondary to BPO, but up to one third of men report no improvement in their LUTS after taking alpha-blockers. Anticholinergics used in addition to alpha-blockers may help improve symptoms but it is uncertain how effective they are. OBJECTIVES: To assess the effects of combination therapy with anticholinergics and alpha-blockers in men with LUTS related to BPO. SEARCH METHODS: We performed a comprehensive search of medical literature, including the Cochrane Library, MEDLINE, Embase, and trials registries, with no restrictions on the language of publication or publication status. The date of the latest search was 7 August 2020. SELECTION CRITERIA: We included randomized controlled trials. Inclusion criteria were men with LUTS secondary to BPO, ages 40 years or older, and a total International Prostate Symptom Score of 8 or greater. We excluded trials of men with a known neurogenic bladder due to spinal cord injury, multiple sclerosis, or central nervous system disease, and those examining medical therapy for men who were treated with surgery for BPO. We performed three comparisons: combination therapy versus placebo, combination therapy versus alpha-blockers monotherapy, and combination therapy versus anticholinergics monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE approach to rate the certainty of evidence. MAIN RESULTS: We included 23 studies with 6285 randomized men across three comparisons. The mean age of participants ranged from 54.4 years to 73.9 years (overall mean age 65.7 years). Of the included studies, 12 were conducted with a single-center setting, while 11 used a multi-center setting. We only found short-term effect (12 weeks to 12 months) of combination therapy based on available evidence. Combination therapy versus placebo: based on five studies with 2369 randomized participants, combination therapy may result in little or no difference in urologic symptom scores (mean difference (MD) -2.73, 95% confidence interval (CI) -5.55 to 0.08; low-certainty evidence). We are very uncertain about the effect of combination therapy on quality of life (QoL) (MD -0.97, 95% CI -2.11 to 0.16; very low-certainty evidence). Combination therapy likely increases adverse events (risk ratio (RR) 1.24, 95% CI 1.04 to 1.47; moderate-certainty evidence); based on 252 adverse events per 1000 participants in the placebo group, this corresponds to 61 more adverse events (95% CI 10 more to 119 more) per 1000 participants treated with combination therapy. Combination therapy versus alpha-blockers alone: based on 22 studies with 4904 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -2.04, 95% CI -3.56 to -0.52; very low-certainty evidence) and QoL (MD -0.71, 95% CI -1.03 to -0.38; very low-certainty evidence). Combination therapy may result in little or no difference in adverse events rate (RR 1.10, 95% CI 0.90 to 1.34; low-certainty evidence); based on 228 adverse events per 1000 participants in the alpha-blocker group, this corresponds to 23 more adverse events (95% CI 23 fewer to 78 more) per 1000 participants treated with combination therapy. Combination therapy compared to anticholinergics alone: based on three studies with 1218 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -3.71, 95% CI -9.41 to 1.98; very low-certainty evidence). Combination therapy may result in an improvement in QoL (MD -1.49, 95% CI -1.88 to -1.11; low-certainty evidence). Combination therapy likely results in little to no difference in adverse events (RR 1.26, 95% CI 0.81 to 1.95; moderate-certainty evidence); based on 115 adverse events per 1000 participants in the anticholinergic alone group, this corresponds to 4 fewer adverse events (95% CI 7 fewer to 13 more) per 1000 participants treated with combination therapy. AUTHORS' CONCLUSIONS: Based on the findings of the review, combination therapy with anticholinergics and alpha-blockers are associated with little or uncertain effects on urologic symptom scores compared to placebo, alpha-blockers, or anticholinergics monotherapy. However, combination therapy may result in an improvement in quality of life compared to anticholinergics monotherapy, but an uncertain effect compared to placebo, or alpha-blockers. Combination therapy likely increases adverse events compared to placebo, but not compared to alpha-blockers or anticholinergics monotherapy. The findings of this review were limited by study limitations, inconsistency, and imprecision. We were unable to conduct any of the predefined subgroup analyses.
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Antagonistas Adrenérgicos alfa/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/complicações , Antagonistas Adrenérgicos alfa/efeitos adversos , Adulto , Idoso , Viés , Antagonistas Colinérgicos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The mitochondrial respiratory chain supercomplex (mitoSC) is a complex super-assembly formed by free complexes on the mitochondrial inner membrane respiratory chain through the interaction between their subunits, mainly including mitoSCI1+III2+IV1-4, mitoSCI1+III2, mitoSCIII2+IV1-2, high molecular weight mitoSC (HMW mitoSC) and mitochondrial metacomplex (mitoMC). mitoSC has been shown to improve the efficiency of electron transport in the respiratory chain and reduce the production of reactive oxygen species. The species and content of mitoSC change in different tissues in aging and many mitochondria-related diseases. By summarizing the structure and function of mitoSC in different tissues of human and mammals, and the changes of mitoSC under conditions of aging, heart disease, type 2 diabetes, cancer and genetic defects, this review focuses on the effects of exercise on mitoSC and its related regulation mechanisms in order to offer an insight for exercise interventions in mitochondria-related diseases.
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Transporte de Elétrons , Exercício Físico , Membranas Mitocondriais/enzimologia , Animais , Humanos , Mitocôndrias , Doenças MitocondriaisRESUMO
This study was undertaken to investigate the effect of exercise training on mitochondrial DNA (mtDNA) oxidative damage and 8-oxoguanine DNA glycosylase-1 (OGG1) expression in skeletal muscle of rats under continuous exposure to hypoxia. Male Sprague-Dawley rats were randomly divided into 4 groups (n = 8): normoxia control group (NC), normoxia training group (NT), hypoxia control group (HC), and hypoxia training group (HT). The hypoxia-treated animals were housed in normobaric hypoxic tent containing 11.3% oxygen for consecutive 4 weeks. The exercise-trained animals were exercised on a motor-driven rodent treadmill at a speed of 15 m/min, 5% grade for 60 min/day, 5 days per week for 4 weeks. The results showed that, compared with NC group, hypoxia attenuated complex I, II, IV and ATP synthase activities of the electron transport chain, and the level of mitochondrial membrane potential in HC group (P < 0.05 or P < 0.01). Moreover, hypoxia decreased mitochondrial OGG1, MnSOD, and GPx activities (P < 0.05 or P < 0.01), whereas elevated reactive oxygen species (ROS) generation and the level of 8-oxo-deoxyguanosine (8-oxodG) in mtDNA (P < 0.01). Furthermore, hypoxia attenuated muscle and mitochondrial [NADâº]/ [NADH] ratio, and SIRT3 protein expression (P < 0.05 or P < 0.01). Compared with HC group, exercise training in hypoxia elevated complex I, II, IV and ATP synthase activities, and the level of mitochondrial membrane potential in HT group (P < 0.05 or P < 0.01). Moreover, exercise training in hypoxia increased MnSOD and GPx activities and mitochondrial OGG1 level (P < 0.01), whereas decreased ROS generation and the level of 8-oxodG in mtDNA (P < 0.01). Furthermore, exercise training in hypoxia increased muscle and mitochondrial [NADâº]/[NADH] ratio, as well as SIRT3 protein expression (P < 0.05 or P < 0.01). These findings suggest that exercise training in hypoxia can decrease hypoxia-induced mtDNA oxidative damage in the skeletal muscle through up-regulating exercise-induced mitochondrial OGG1 and antioxidant enzymes. Exercise training in hypoxia may improve hypoxia tolerance in skeletal muscle mitochondria via elevating [NADâº]/[NADH] ratio and SIRT3 expression.
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DNA Glicosilases/metabolismo , Hipóxia/fisiopatologia , Mitocôndrias Musculares/patologia , Estresse Oxidativo , Condicionamento Físico Animal , Animais , DNA Mitocondrial/química , Glutationa Peroxidase/metabolismo , Guanina/análogos & derivados , Guanina/metabolismo , Masculino , Músculo Esquelético/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Regular endurance exercise promotes favorable structure and metabolism adaptations in contracting organ (skeletal muscle) and "far-sited" organ (heart, brain, liver, adipose tissue). Exercise induced skeletal muscle remodeling by activating a series of signaling and transcriptional circuitry (e. g., PPARδ, AMPK, SIRT1 and PGC-1α). In addition, contracting skeletal muscle is an endocrine organ producing and releasing myokines (e. g. IL-6, BDNF and Irisin), which work in a hormone-like fashion, exerting specific endocrine effects on " far-sited" organ. It has been suggested that myokines may contribute to exercise-induced protection against several chronic disease. In this review, we discuss recent discoveries that raise the possibility of synthetically mimicking exercise with pathway-specific drugs to improve health.
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Exercício Físico , Promoção da Saúde , Tecido Adiposo , Humanos , Fígado , Músculo Esquelético , Transdução de SinaisRESUMO
Skeletal muscle is a heterogeneous tissue composed of different types of muscle fibers, demonstrating substantial plasticity. Physiological or pathological stimuli can induce transitions in muscle fiber types. However, the precise regulatory mechanisms behind these transitions remains unclear. This paper reviews the classification and characteristics of muscle fibers, along with the classical mechanisms of muscle fiber type transitions. Additionally, the role of exercise-induced muscle fiber type transitions in disease intervention is reviewed. Epigenetic pathways mediate cellular adaptations and thus represent potential targets for regulating muscle fiber type transitions. This paper focuses on the mechanisms by which epigenetic modifications couple mitochondrial function and contraction characteristics. Reactive Oxygen Species (ROS) are critical signaling regulators for the health-promoting effects of exercise. Finally, we discuss the role of exercise-induced ROS in regulating epigenetic modifications and the transition of muscle fiber types.
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Mitocôndrias , Fibras Musculares Esqueléticas , Espécies Reativas de Oxigênio/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Epigênese GenéticaRESUMO
A dynamic prediction model for the content of Baicalin in Shang Jie plasters extract solutions was developed using near-infrared spectroscopy in transmission mode. Sixty five spectra were obtained through near-infrared transmission mode during extracting process. Refering to the content of Baicalin performed by reversed-phase high performance liquid chromatography (HPLC), the calibration model was developed with the application of partial least squares regression algorithm (PLSR). The constructed model was validated by 30 samples; some parameters of the calibration model were optimized by cross-validation. The root mean square error (RMSECV) of Baicalin was 0.006 8 mg x g(-1), the correlation coefficient (R) was 0.9991, and the optimal dimension factor was 8; After predicted by test set, the root mean square error (RMSEP) and correlation coefficient (R) of prediction obtained were 0.009 2 mg x g(-1) and 0.998 7 respectively. This work demonstrated that NIR spectroscopy combined with PLS could be used for the determination of Baicalin in Shang Jie plasters extract.
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Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Análise dos Mínimos Quadrados , Modelos Teóricos , Controle de QualidadeRESUMO
The mitochondrial unfolded protein response (UPRmt) and mitophagy are two mitochondrial quality control (MQC) systems that work at the molecular and organelle levels, respectively, to maintain mitochondrial homeostasis. Under stress conditions, these two processes are simultaneously activated and compensate for each other when one process is insufficient, indicating mechanistic coordination between the UPRmt and mitophagy that is likely controlled by common upstream signals. This review focuses on the molecular signals regulating this coordination and presents evidence showing that this coordination mechanism is impaired during aging and promoted by exercise. Furthermore, the bidirectional regulation of reactive oxygen species (ROS) and AMPK in modulating this mechanism is discussed. The hierarchical surveillance network of MQC can be targeted by exercise-derived ROS to attenuate aging, which offers a molecular basis for potential therapeutic interventions for sarcopenia.
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Introduction: Skeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slow-twitch muscles than in fast-twitch muscles during IR development, while the mechanisms involved remain unclear. Therefore, we investigated the role of the mitochondrial unfolded protein response (UPRmt) in the distinct resistance of two types of muscle in IR. Methods: Male Wistar rats were divided into high-fat diet (HFD) feeding and control groups. We measured glucose transport, mitochondrial respiration, UPRmt and histone methylation modification of UPRmt-related proteins to examine the UPRmt in the slow fiber-enriched soleus (Sol) and fast fiber-enriched tibialis anterior (TA) under HFD conditions. Results: Our results indicate that 18 weeks of HFD can cause systemic IR, while the disturbance of Glut4-dependent glucose transport only occurred in fast-twitch muscle. The expression levels of UPRmt markers, including ATF5, HSP60 and ClpP, and the UPRmt-related mitokine MOTS-c were significantly higher in slow-twitch muscle than in fast-twitch muscle under HFD conditions. Mitochondrial respiratory function is maintained only in slow-twitch muscle. Additionally, in the Sol, histone methylation at the ATF5 promoter region was significantly higher than that in the TA after HFD feeding. Conclusion: The expression of proteins involved in glucose transport in slow-twitch muscle remains almost unaltered after HFD intervention, whereas a significant decline of these proteins was observed in fast-twitch muscle. Specific activation of the UPRmt in slow-twitch muscle, accompanied by higher mitochondrial respiratory function and MOTS-c expression, may contribute to the higher resistance to HFD in slow-twitch muscle. Notably, the different histone modifications of UPRmt regulators may underlie the specific activation of the UPRmt in different muscle types. However, future work applying genetic or pharmacological approaches should further uncover the relationship between the UPRmt and insulin resistance.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças Musculares , Ratos , Masculino , Animais , Insulina/metabolismo , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Resistência à Insulina/fisiologia , Dieta Hiperlipídica/efeitos adversos , Ratos Wistar , Diabetes Mellitus Tipo 2/metabolismo , Histonas/metabolismo , Músculo Esquelético/metabolismo , Glucose/metabolismo , Resposta a Proteínas não DobradasRESUMO
BACKGROUND: As a common complication of sepsis, sepsis-associated encephalopathy (SAE) is characterized by diffuse brain dysfunction and neurological damage and closely associated with long-term cognitive dysfunction. The dysregulated host response triggered by neurotoxicity of microglia is an important cause of diffuse brain dysfunction in SAE. Resveratrol glycoside has anti-inflammatory and antioxidant effects. However, there is no evidence whether resveratrol glycoside could alleviate SAE. METHODS: LPS administration was used to induce SAE in mice. Step-down test (SDT) and Morris water maze test (MWM) were performed to evaluate the cognitive function of mice with SAE. Western blot and immunofluorescence were used to reveal the endoplasmic reticulum stress (ERS) regulation. Microglia cell line BV-2 was used to validate the effect of resveratrol glycoside on LPS-stimulated ERS in vitro. RESULTS: Compared with the control group, LPS-stimulated mice had decreased cognitive function, but this phenomenon was well reversed by resveratrol glycoside administration, in which the SDT assay showed longer retention time, both in short-term memory (STM) and long-term memory (LTM). Western blot indicated that the expression of ER stress-related protein PERK/CHOP in LPS-stimulated mice were significantly increased, while that in the resveratrol glycoside-treated group were relieved. Furthermore, Immunofluorescence revealed resveratrol glycoside mainly worked on microglia in mediating the ER stress, in which the expression of PERK/CHOP were significantly inhibited in resveratrol glycoside group mice. In vitro, BV2 showed consistent results with the aforementioned. CONCLUSION: Resveratrol glycoside could alleviate the cognitive dysfunction caused by LPS-induced SAE, mainly by inhibiting the ER stress and maintaining the homeostasis of ER function of microglia.
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Disfunção Cognitiva , Encefalopatia Associada a Sepse , Sepse , Camundongos , Animais , Resveratrol/farmacologia , Microglia , Lipopolissacarídeos/farmacologia , Glicosídeos/metabolismo , Glicosídeos/farmacologia , Sepse/metabolismo , Encefalopatia Associada a Sepse/metabolismo , Estresse do Retículo EndoplasmáticoRESUMO
Background: Less than 1% of children develop femoral neck fractures (FNF), making them uncommon. However, they may have dangerous side effects, like avascular necrosis. Even though several risk factors for postoperative avascular necrosis have been identified, there is still debate regarding them. In this investigation, a meta-analysis was performed to examine the potential causes of postoperative avascular necrosis in children with FNF. Methods: We conducted a thorough literature search to find risk factors for avascular necrosis (AVN) after internal fixation of pediatric FNF. Until December 2022, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Orthosearch, and Sinomed. Software Zotero 6.0 and Stata 17.0 were used to organise and synthesise the data. Finally, a sensitivity and publication bias test was carried out. Results: Our study includes a total of 15 case-control studies involving 814 patients. The risk of postoperative AVN increased with age at fracture encounter (95% CI: 0.64-1.88, P = 0.0003), initial fracture displacement (95% CI: 1.87-9.54, P = 0.0005), and poor fracture reduction (95% CI:1.95-22.34, P = 0.0024) were risk factors for postoperative AVN. There was no significant relationship between gender and postoperative AVN (95% CI: 0.52-1.31, P = 0.41). Conversely, Postoperative AVN and reduction methods have no connection with each other (95% CI: 0.77-2.66, P = 0.25), procedure time (95% CI: 0.43-2.99, P = 0.16), or injury mechanism (95% CI: 0.32-2.26, P = 0.75). The incidence of post-operative AVN varies between Delbet fracture types (95% CI: 0.15-0.31, P < 0.0001), with the overall trend being that the incidence of post-operative AVN is highest for type II, lowest for type IV, and close for types I and III, but it is not clear which type of fracture is the independent risk factor. Funnel plots indicate no significant publication bias. Conclusions: In line with this study, About 26% of children who underwent surgery for a femoral neck fracture suffered postoperative AVN. The main risk factors for AVN were the child's age, the initial displacement of the fractures, and poorly reduced fractures. The risk of AVN did not significantly correlate with gender, the time of the procedure, reduction methods or the mechanism of injury. The overall trend in the incidence of postoperative AVN for the different Delbet types of fracture is that the incidence of postoperative AVN is highest for type II, lowest for type IV, and close for types I and III, but it is not clear which type of fracture is the independent risk factor.
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The combination of materials with different functions is an optimal strategy for synchronously removing various indoor pollutants. For multiphase composites, exposing all components and their phase interfaces fully to the reaction atmosphere is a critical problem that needs to be solved urgently. Here, a bimetallic oxide Cu2O@MnO2 with exposed phase interfaces was prepared by a surfactant-assisted two-step electrochemical method, which shows a composite structure of non-continuously dispersed Cu2O particles anchored on flower-like MnO2. Compared with the pure catalyst MnO2 and bacteriostatic agent Cu2O, Cu2O@MnO2 respectively shows superior dynamic formaldehyde (HCHO) removal efficiency (97.2% with a weight hourly space velocity of 120 000 mL g-1 h-1) and pathogen inactivation ability (the minimum inhibitory concentration for 104 CFU mL-1 Staphylococcus aureus is 10 µg mL-1). According to material characterization and theoretical calculation, its excellent catalytic-oxidative activity is attributable to the electron-rich region at the phase interface which is fully exposed to the reaction atmosphere, inducing the capture and activation of O2 on the material surface, and then promoting the generation of reactive oxygen species that can be used for the oxidative-removal of HCHO and bacteria. Additionally, as a photocatalytic semiconductor, Cu2O further enhances the catalytic ability of Cu2O@MnO2 under the assistance of visible light. This work will provide efficient theoretical guidance and a practical basis for the ingenious construction of multiphase coexisting composites in the field of multi-functional indoor pollutant purification strategies.
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Background: Skeletal maturity can evaluate the growth and development potential of children and provide a guide for the management of adolescent idiopathic scoliosis (AIS). Recent studies have demonstrated the advantages of the Humeral Head Ossification System (HHOS) and the Proximal Femur Maturity Index (PFMI), based on standard scoliosis films, in the management of AIS patients. We further assessed the HHOS and the PFMI method's reliability in the interrater and intrarater. Methods: The data from 38 patients, including the humeral head and proximal femur on standard scoliosis films, were distributed to the eight raters in the form of a PowerPoint presentation. On 38 independent standard spine radiographs, raters utilized the HHOS and PFMI to assign grades. The PPT sequence was randomly changed and then reevaluated 2 weeks later. For every system, the 95% confidence interval (95% CI) and intraclass correlation coefficient (ICC) were calculated to evaluate the interrater and intrarater reliability. Results: The HHOS was extremely reliable, with an intraobserver ICC of 0.802. In the first round, the interobserver ICC reliability for the HHOS was 0.955 (0.929-0.974), while in the second round, it was 0.939 (0.905-0.964). The PFMI was extremely reliable, with an intraobserver ICC of 0.888. In the first round, the interobserver ICC reliability for the PFMI was 0.967 (0.948-0.981), while in the second round, it was 0.973 (0.957-0.984). Conclusions: The HHOS and PFMI classiï¬cations had excellent reliability. These two methods are beneficial to reduce additional exposure to radiation and expense for AIS. There are advantages and disadvantages to each classification. Clinicians should choose a personalized and reasonable method to assess skeletal maturity, which will assist in the management of adolescent scoliosis patients.
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The mitochondrial unfolded protein response (UPRmt) can repair and remove misfolded or unfolded proteins in mitochondria and enhance mitochondrial protein homeostasis. Reactive oxygen species (ROS) produced by regular exercise is a crucial signal for promoting health, and skeletal muscle mitochondria are the primary source of ROS during exercise. To verify whether UPRmt is related to ROS produced by mitochondria in skeletal muscle during regular exercise, we adapted MitoTEMPO, mitochondrially targeted antioxidants, and ROS production by mitochondria. Our results showed that mitochondrial ROS is the key factor for activating UPRmt in different pathways.
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Mitocôndrias Musculares/metabolismo , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Resposta a Proteínas não Dobradas , Humanos , Mitocôndrias/metabolismo , Células Musculares/fisiologiaRESUMO
Aging causes degenerative changes such as epigenetic changes and mitochondrial dysfunction in skeletal muscle. Exercise can upregulate muscle mitochondrial homeostasis and enhance antioxidant capacity and represents an effective treatment to prevent muscle aging. Epigenetic changes such as DNA methylation, histone posttranslational modifications, and microRNA expression are involved in the regulation of exercise-induced adaptive changes in muscle mitochondria. Reactive oxygen species (ROS) play an important role in signaling molecules in exercise-induced muscle mitochondrial health benefits, and strong evidence emphasizes that exercise-induced ROS can regulate gene expression via epigenetic mechanisms. The majority of mitochondrial proteins are imported into mitochondria from the cytosol, so mitochondrial homeostasis is regulated by nuclear epigenetic mechanisms. Exercise can reverse aging-induced changes in myokine expression by modulating epigenetic mechanisms. In this review, we provide an overview of the role of exercise-generated ROS in the regulation of mitochondrial homeostasis mediated by epigenetic mechanisms. In addition, the potential epigenetic mechanisms involved in exercise-induced myokine expression are reviewed.
Assuntos
Mitocôndrias , Músculo Esquelético , Epigênese Genética , Homeostase , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Background: Identifying a high-risk group of older people before surgical procedures is very important. The study aimed to explore the association between the age-adjusted Charlson comorbidity index (ACCI) and all-cause mortality and readmission among older Chinese surgical patients (age ≥65 years). Methods: A large-scale cohort study was performed in 25 general public hospitals from six different geographic regions of China. Trained registered nurses gathered data on clinical and sociodemographic characteristics. All-cause mortality was recorded when patients died during hospitalization or during the 90-day follow-up period. Readmission was also tracked from hospital discharge to the 90-day follow-up. The ACCI, in assessing comorbidities, was categorized into two groups (≥5 vs. <5). A multiple regression model was used to examine the association between the ACCI and all-cause mortality and readmission. Results: There were 3,911 older surgical patients (mean = 72.46, SD = 6.22) in our study, with 1,934 (49.45%) males. The average ACCI score was 4.77 (SD = 1.99), and all-cause mortality was 2.51% (high ACCI = 5.06% vs. low ACCI = 0.66%, P < 0.001). After controlling for all potential confounders, the ACCI score was an independent risk factor for 90-day hospital readmission (OR = 1.18, 95% CI: 1.14, 1.23) and 90-day all-cause mortality (OR = 1.26, 95% CI: 1.16-1.36). Furthermore, older surgical patients with a high ACCI (≥5) had an increased risk of all-cause mortality (OR = 6.13, 95% CI: 3.17, 11.85) and readmission (OR = 2.13, 95% CI: 1.78, 2.56) compared to those with a low ACCI (<5). The discrimination performance of the ACCI was moderate for mortality (AUC:0.758, 95% CI: 0.715-0.80; specificity = 0.591, sensitivity = 0.846) but poor for readmission (AUC: 0.627, 95% CI: 0.605-0.648; specificity = 0.620; sensitivity = 0.590). Conclusions: The ACCI is an independent risk factor for all-cause mortality and hospital readmission among older Chinese surgical patients and could be a potential risk assessment tool to stratify high-risk older patients for surgical procedures.