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1.
J Neuroinflammation ; 21(1): 138, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802927

RESUMO

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.


Assuntos
Aquaporina 4 , Astrócitos , Eixo Encéfalo-Intestino , Hiperamonemia , Encefalopatia Associada a Sepse , Animais , Camundongos , Aquaporina 4/metabolismo , Aquaporina 4/genética , Aquaporina 4/biossíntese , Astrócitos/metabolismo , Hiperamonemia/metabolismo , Encefalopatia Associada a Sepse/metabolismo , Masculino , Eixo Encéfalo-Intestino/fisiologia , Camundongos Endogâmicos C57BL , Amônia/metabolismo , Amônia/sangue , Encéfalo/metabolismo , Transplante de Microbiota Fecal
2.
J Clin Lab Anal ; 36(5): e24361, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35318719

RESUMO

BACKGROUND: Recent studies showed that inflammation and immunity might play essential roles in the progression of intracerebral hemorrhage (ICH). However, the underlying mechanisms for changes at the cellular and molecular levels after ICH remain unclear. METHODS: We downloaded the microarray dataset of ICH from the Gene Expression Omnibus (GEO) database. The differential expression gene analysis was obtained by weighted gene co-expression network analysis (WGCNA). We got the hub genes and performed the biological functions and signaling pathways of these genes by Metascape. GSVA algorithm was used to evaluate the potential physical function of time-varying ICH samples. We used single-sample gene set enrichment analysis (ssGSEA) to assess the immune signatures infiltration and analyzed the correlation between hub genes and immune signatures. RESULTS: The data sets of all 22 ICH samples in GSE125512 were examined by the WGCNA R package. We finally screened five hub genes (GAPDH, PF4, SELP, APP, and PPBP) in the royal blue module. Metascape analysis displayed the biological processes related to inflammation and immunology. Cell adhesion molecule binding, myeloid leukocyte activation, CXCR chemokine receptor binding, and regulation of cytokine production were the most enriched pathophysiological process. The immune signatures infiltration analyses showed that ICH patients' early and late samples had different activity and abundance of immune-related cells and types. CONCLUSIONS: GAPDH, PF4, SELP, APP, and PPBP are identified as potential biomarkers for predicting the progression of ICH. This study may help us better understand the immunologic mechanism and shed new light on the promising approaches of immunotherapy for ICH patients.


Assuntos
Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Biomarcadores , Hemorragia Cerebral/genética , Humanos , Inflamação
3.
Paediatr Anaesth ; 32(4): 531-538, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35049111

RESUMO

BACKGROUND AND AIM: The bend angle of a lighted stylet is an important factor for successful orotracheal intubation. The aim of this study was to test the differences in the success of endotracheal intubation using lighted stylet with 70° versus 90° bend angles in children aged 4-6 years with normal airways. METHODS: A total of 136 children with normal airways required orotracheal intubation were enrolled and were randomly allocated to the 90° or 70° bend angle groups. The first-attempt success rate was assessed as the primary outcome. The intubation time, lighted stylet search time, lighted stylet withdrawal time, hemodynamic responses, and perioperative complications were recorded as secondary outcomes. RESULTS: All intubations were completed within three attempts (the 90° group, 63/5/0; the 70° group, 55/11/2). The first-attempt success rate was higher in the 90° group than that in the 70° group (92.6% [63/68 patients] versus 80.9% [55/68 patients], respectively; risk ratio, 1.15; 95% CI, 1.01-1.31; p = .04). Esophageal entry occurred in nine of 83 intubation attempts in the 70° group and two of 73 intubation attempts in the 90° group (risk ratio, 1.09; 95% CI, 1.01-1.19; p = .04). The intubation time and the lighted stylet search time were significantly shorter in the 90° group than that in the 70° group (intubation time: 12.2 ± 2.0 s versus 14.9 ± 2.6 s, respectively; mean difference, 2.65; 95% CI, 1.87-3.43; p < .01; effect size, 1.16; lighted stylet search time: 5.4 ± 1.0 s versus 8.0 ± 1.6 s, respectively; mean difference, 2.66; 95% CI, 2.21-3.12; p < .01; effect size, 1.95). CONCLUSIONS: Lighted stylet intubation with a 90° bend angle improved the first-attempt success rate and reduced esophageal intubation in children aged 4-6 years with normal airways.


Assuntos
Intubação Intratraqueal , Laringoscópios , Criança , Humanos , Intubação Intratraqueal/efeitos adversos , Laringoscópios/efeitos adversos , Estudos Prospectivos
4.
Mol Cell Biochem ; 469(1-2): 41-51, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32323054

RESUMO

Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, is a commonly used anesthetic drug in surgical procedures. Previous studies have indicated that DEX exerts neuroprotective effects while the detailed mechanism has not been fully elucidated. Here, we aim to study the role of lncRNA SHNG16 in DEX-induced brain protection and its underlying molecular mechanism. The rats underwent middle cerebral artery occlusion (MCAO) surgery and oxygen-glucose deprivation (OGD)-treated HT22 hippocampal neurons were treated with DEX, respectively. CCK8 was used to evaluate cell viability. sh-SHNG16 as well as miR-10b-5p mimics were transfected into hippocampal neurons to further explore the bio-function of SNHG16 and miR-10b-5p in vitro. Furthermore, the interactions between SHNG16 and miR-10b-5p, miR-10b-5p and BDNF gene were confirmed by dual-luciferase report assay. Our data revealed that DEX attenuated neurological damage of the MCAO rats and also increased the cell viability of the neurons significantly. Besides, expression of SHNG16 and BDNF were both downregulated while miR-10b-5p was upregulated in MCAO brain tissues or OGD treated neurons. DEX inhibited miR-10b-5p expression but increased SHNG16 and BDNF levels with a dosage effect. After transfection with sh-SHNG16 or miR-10b-5p mimics, the expression of BDNF protein was downregulated, accompanied with decreased neuron viability. Dual-luciferase assay showed that SHNG16 targeted on miR-10b-5p, which also could bind directly to the 3'-UTR sites of BDNF and negatively regulate its expression. In conclusion, DEX exerts neuroprotective in ischemic stroke via improving neuron damage, the underlying mechanism may be upregulating SHNG16 and BDNF via sponging miR-10b-5p.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dexmedetomidina/farmacologia , Hipocampo/efeitos dos fármacos , MicroRNAs/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Hipóxia Celular/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hipocampo/citologia , Hipocampo/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Camundongos , MicroRNAs/genética , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , RNA Longo não Codificante/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos
5.
J Clin Anesth ; 98: 111590, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39178493

RESUMO

BACKGROUND: The video laryngoscope (VLS) has been proven to be an effective insertion device for airway management. However, no laryngoscope has been specifically designed for the placement of the laryngeal mask airway (LMA). We improved the current VLS and developed a novel VLS method. This study aimed to evaluate the clinical efficacy of an improved VLS for inserting a flexible laryngeal mask airway (F-LMA) compared with the standard blind method. METHODS: One hundred and fifty-seven patients who underwent F-LMA insertion under general anesthesia were randomly assigned to either the standard blind insertion technique (group B) or VLS -assisted insertion (group VL). First attempt success rates were recorded. Secondary outcomes included oropharyngeal leakage pressure (OLP), fiberoptic view, insertion time, position adjustment, reinsertion rate, and postoperative airway morbidity. RESULTS: The first-attempt success rate was higher in group VL than that in group B (99% vs. 86%; p = 0.002). The OLP was significantly higher in the VLS-guided technique (26.4 ± 5.1 vs 23.8 ± 4.4 cmH2O, p = 0.002). The fiberoptic view was significantly better in the group VL (p < 0.001) and required less readjustment and reinsertion to establish an effective airway (p < 0.001). The insertion time was shorter in the group B than that in group VL (33.9 vs 41.3 s, p < 0.001). Hemodynamic stress responses and postoperative airway complications did not differ between the two groups. CONCLUSIONS: The new VLS-guided insertion technology has a high success rate, achieves greater OLP, and provides an ideal anatomical position with minimal adjustment, without increasing the risk of hemodynamic stress or adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Registry (registration number: ChiCTR2300075866; https://www.chictr.org.cn).


Assuntos
Anestesia Geral , Intubação Intratraqueal , Máscaras Laríngeas , Laringoscópios , Humanos , Máscaras Laríngeas/efeitos adversos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Anestesia Geral/instrumentação , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Intubação Intratraqueal/efeitos adversos , Adulto , Desenho de Equipamento , Idoso , Tecnologia de Fibra Óptica , Laringoscopia/métodos , Laringoscopia/instrumentação , Laringoscopia/efeitos adversos , Manuseio das Vias Aéreas/métodos , Manuseio das Vias Aéreas/instrumentação , Técnicas e Procedimentos Assistidos por Vídeo
6.
Shock ; 62(4): 470-479, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38888575

RESUMO

ABSTRACT: Background: Despite rapid advances in treatment, sepsis currently remains a major public health challenge worldwide. Over the past several years, there has been an increase in the clinical incidence of sepsis, as well as an increase in hospitalization rates, which bear the majority of the economic burden associated with sepsis. Sepsis is a public health burden due to the high fatality rates and accompanying morbidity. However, the sepsis-related mortality rates have fallen steadily over the years. One of the most common organs to fail in patients with sepsis is the kidney, and acute kidney injury (AKI) is associated with high mortality rates. This study's primary goal was to assess the impact of AKI on the evolution and outcome of hospitalization of patients with sepsis. Methods: Adults (≥18 years) hospitalized for sepsis in the United States between 2010 and 2019 were retrospectively analyzed using the nationally representative Nationwide Inpatient Sample database. Sepsis and AKI were defined using the codes of the International Classification of Diseases, Ninth Revision, Clinical Modification and the International Classification of Diseases, Tenth Revision, Clinical Modification. Results: Of the 4,258,360 outcomes, 3,946,048 met the inclusion criteria. The prevalence of AKI among sepsis inpatients increased from 39.10% in 2010 to 41% in 2019, but the impact of AKI on mortality declined over time, with in-hospital mortality from AKI among sepsis inpatients decreasing from 26.30% in 2010 to 16.30% in 2019. Hospitalizations linked to AKI were substantially more likely to involve infection sites such as the urinary tract, gastrointestinal tract, and endocarditis. Numerous pathogenic floras, including Escherichia coli , Staphylococcus aureus , Streptococcal , Enterococcus , and Pseudomonas , had greater rates among sepsis-related contacts with AKI. Furthermore, compared to hospitalization without comorbid AKI, the median total hospital charges and length of stay days for sepsis hospitalization with comorbid AKI were greater. Conclusion: With time, patients with sepsis have a higher frequency of AKI and a corresponding decline in mortality.


Assuntos
Injúria Renal Aguda , Hospitalização , Sepse , Humanos , Sepse/epidemiologia , Sepse/mortalidade , Sepse/complicações , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estados Unidos/epidemiologia , Mortalidade Hospitalar/tendências , Adulto , Pacientes Internados , Idoso de 80 Anos ou mais
7.
Biomed Res Int ; 2020: 2148706, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33145342

RESUMO

BACKGROUND: Endotoxin-associated acute kidney injury (AKI), a disease characterized by marked oxidative stress and inflammation disease, is a major cause of mortality in critically ill patients. Mitochondrial fission and pyroptosis often occur in AKI. However, the underlying biological pathways involved in endotoxin AKI remain poorly understood, especially those related to mitochondrial dynamics equilibrium disregulation and pyroptosis. Previous studies suggest that heme oxygenase- (HO-) 1 confers cytoprotection against AKI during endotoxic shock, and PTEN-induced putative kinase 1 (PINK1) takes part in mitochondrial dysfunction. Thus, in this study, we examine the roles of HO-1/PINK1 in maintaining the dynamic process of mitochondrial fusion/fission to inhibit pyroptosis and mitigate acute kidney injury in rats exposed to endotoxin. METHODS: An endotoxin-associated AKI model induced by lipopolysaccharide (LPS) was used in our study. Wild-type (WT) rats and PINK1 knockout (PINK1KO) rats, respectively, were divided into four groups: the control, LPS, Znpp+LPS, and Hemin+LPS groups. Rats were sacrificed 6 h after intraperitoneal injecting LPS to assess renal function, oxidative stress, and inflammation by plasma. Mitochondrial dynamics, morphology, and pyroptosis were evaluated by histological examinations. RESULTS: In the rats with LPS-induced endotoxemia, the expression of HO-1 and PINK1 were upregulated at both mRNA and protein levels. These rats also exhibited inflammatory response, oxidative stress, mitochondrial fission, pyroptosis, and decreased renal function. After upregulating HO-1 in normal rats, pyroptosis was inhibited; mitochondrial fission and inflammatory response to oxidative stress were decreased; and the renal function was improved. The effects were reversed by adding Znpp (a type of HO-1 inhibitor). Finally, after PINK1 knockout, there is no statistical difference in the LPS-treated group and Hemin or Znpp pretreated group. CONCLUSIONS: HO-1 inhibits inflammation response and oxidative stress and regulates mitochondria fusion/fission to inhibit pyroptosis, which can alleviate endotoxin-induced AKI by PINK1.


Assuntos
Injúria Renal Aguda/genética , Heme Oxigenase (Desciclizante)/genética , Dinâmica Mitocondrial/genética , Proteínas Quinases/genética , Piroptose/genética , Choque Séptico/genética , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/enzimologia , Injúria Renal Aguda/patologia , Animais , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Heme Oxigenase (Desciclizante)/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/patologia , Lipocalina-2/genética , Lipocalina-2/metabolismo , Lipopolissacarídeos/administração & dosagem , Masculino , Dinâmica Mitocondrial/efeitos dos fármacos , Estresse Oxidativo , Proteínas Quinases/deficiência , Protoporfirinas/farmacologia , Piroptose/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Choque Séptico/induzido quimicamente , Choque Séptico/enzimologia , Choque Séptico/patologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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