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1.
World J Emerg Med ; 15(3): 206-213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855370

RESUMO

BACKGROUND: This study aims to explore whether Xuebijing (XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism. METHODS: A rat model of sepsis was established by cecal ligation and puncture (CLP). A total of 30 male SD rats were divided into four groups: sham group, CLP group, XBJ + axitinib group, and XBJ group. XBJ was intraperitoneally injected 2 h before CLP. Hemodynamic data (blood pressure and heart rate) were recorded. The intestinal microcirculation data of the rats were analyzed via microcirculation imaging. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in the rats. Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats. The expression of vascular endothelial growth factor A (VEGF-A), phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt), and phosphorylated Akt (p-Akt) in the small intestine was analyzed via Western blotting. RESULTS: XBJ improved intestinal microcirculation dysfunction in septic rats, alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa, and reduced the systemic inflammatory response. Moreover, XBJ upregulated the expression of VEGF-A, p-PI3K/total PI3K, and p-Akt/total Akt in the rat small intestine. CONCLUSION: XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

2.
Int Immunopharmacol ; 118: 110049, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37018980

RESUMO

PURPOSE: Sepsis has complex pathophysiological mechanisms that bring new challenges in the treatment of sepsis at a time when the intestinal microcirculation in sepsis is receiving increasing attention. Dl-3-n-butylphthalide (NBP), which is a drug that can improve multiorgan ischemic diseases, is also worth examining to improve the intestinal microcirculation in sepsis. METHODS: In this study, male Sprague-Dawley rats were divided into the sham group (n = 6), CLP group (n = 6), NBP group (n = 6) and NBP + LY294002 group (n = 6). The rat model of severe sepsis was established by cecal ligation and puncture (CLP). Abdominal wall incisions and sutures were performed in the first group, and CLP was performed in the latter three groups. Normal saline/NBP/NBP + LY294002 solution was injected intraperitoneally 2 h or 1 h before modeling. Hemodynamic data (blood pressure and heart rate) were recorded at 0, 2, 4 and 6 h. Sidestream dark field (SDF) imaging and the Medsoft System were used to observe the intestinal microcirculation of rats and obtain data at 0, 2, 4, and 6 h. Six hours after the model was established, the serum levels of TNF-α and IL-6 were measured to evaluate the level of systemic inflammation. Pathological damage to the small intestine was evaluated by electron microscopy and histological analysis. The expression levels of P-PI3K, PI3K, P-AKT, AKT, LC3 and p62 in the small intestine were analyzed by Western blotting. The expressions of P-PI3K, P-AKT, LC3 and P62 in small intestine were detected by immunohistochemical staining. RESULTS: NBP improved intestinal microcirculation disturbances in septic rats, alleviated the systemic inflammatory response, reduced the destruction of the small intestinal mucosa and the disruption of microvascular endothelial cells, and alleviated autophagy in vascular endothelial cells. NBP increased the ratio of P-PI3K/total PI3K, P-AKT/total AKT, and P62/ß-actin and decreased the ratio of LC3 II/LC3 I. CONCLUSION: NBP ameliorated intestinal microcirculation disturbances and the destruction of small intestinal vascular endothelial cells in septic rats by activating the PI3K/Akt signaling pathway and regulating autophagy.


Assuntos
Enteropatias , Sepse , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células Endoteliais/metabolismo , Microcirculação , Transdução de Sinais/fisiologia , Autofagia , Sepse/tratamento farmacológico , Sepse/metabolismo
3.
World J Emerg Med ; 13(5): 355-360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119776

RESUMO

BACKGROUND: This study aimed to establish an effective nomogram to predict the survival of heat stroke (HS) based on risk factors. METHODS: This was a retrospective, observational multicenter cohort study. We analyzed patients diagnosed with HS, who were treated between May 1 and September 30, 2018 at 15 tertiary hospitals from 11 cities in Northern China. RESULTS: Among the 175 patients, 32 patients (18.29%) died before hospital discharge. After the univariate analysis, mechanical ventilation, initial mean arterial pressure <70 mmHg, maximum heart rate, lab results on day 1 (white blood cell count, alanine aminotransferase, creatinine), and Glasgow admission prediction score were included in multivariate analysis. Multivariate Cox regression showed that invasive ventilation, initial mean arterial pressure <70 mmHg (1 mmHg=0.133 kPa), and Glasgow admission prediction score were independent risk factors for HS. The nomogram was established for predicting 7-d and 14-d survival in the training cohort. The nomogram exhibited a concordance index (C-index) of 0.880 (95% confidence interval [95% CI] 0.831-0.930) by bootstrapping validation (B=1,000). Furthermore, the nomogram performed better when predicting 14-d survival, compared to 7-d survival. The prognostic index cut-off value was set at 2.085, according to the operating characteristic curve for overall survival prediction. The model showed good calibration ability in the internal and external validation datasets. CONCLUSION: A novel nomogram, integrated with prognostic factors, was proposed; it was highly predictive of the survival in HS patients.

4.
Aging (Albany NY) ; 12(6): 5411-5422, 2020 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-32221047

RESUMO

OBJECTIVE: This study was aimed at investigating the regulation of mitochondrial function by histone deacetylase 6 (HDAC6) and the role of HDAC6 in the development and progression of sepsis. RESULTS: HDAC6 downregulated PHB1 and subsequently promoted the development of CLP-induced sepsis. Inhibition of HDAC6 significantly attenuated CLP-induced sepsis through inhibition of mitochondrial dysfunction and reduced oxidant production, thus protecting the rats from oxidative injury. CONCLUSIONS: In this sepsis model, HDAC6 inhibits the expression and function of PHB1 and alters the function of the mitochondrial respiratory chain mediated by PHB1, thus enhancing the production of oxidants and increasing oxidative stress and thereby leading to severe oxidative injury in multiple organs. METHODS: The expression of HDAC6 and prohibitin 1 (PHB1) in humans and in a rat model of sepsis was measured by quantitative reverse-transcription PCR and western blotting. Sepsis induction by cecal ligation and puncture (CLP) was confirmed by histological analysis. Concentrations of different sepsis markers were measured by an enzyme-linked immunosorbent assay, and mitochondrial function was assessed via the mitochondrial respiratory control rate.


Assuntos
Desacetilase 6 de Histona/metabolismo , Mitocôndrias/metabolismo , Proteínas Repressoras/metabolismo , Sepse/metabolismo , Idoso , Animais , Western Blotting , Estudos de Casos e Controles , Ceco/patologia , Respiração Celular , China , Modelos Animais de Doenças , Feminino , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Proibitinas , Ratos , Ratos Sprague-Dawley , Sepse/patologia
5.
Biomed Environ Sci ; 31(8): 596-607, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30231964

RESUMO

OBJECTIVE: A new technique of transthoracic lung ultrasonography (TLS) has emerged and demonstrated promising results in acute heart failure diagnosis at an early stage. However, the diagnostic value of ultrasound lung comets (ULCs) for acute heart failure (AHF) performed in busy emergency department (ED) is uncertain. The present meta-analysis aimed to assess the diagnostic efficiency of ULCs in AHF. METHODS: We conducted a search on online journal databases to collect the data on TLS performed for diagnosing AHF published up to the end of July 2017. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curve were calculated. The post-test probability of AHF was calculated by using Bayes analysis. RESULTS: We enrolled a total of 15 studies involving 3,309 patients. The value of sensitivity, specificity, PLR, NLR, DOR, area under the SROC curve, and Q* index was 85%, 91%, 8.94, 0.14, 67.24, 0.9587, and 0.9026, respectively. We detected significant heterogeneity among included studies, and therefore, all these results were analyzed under the random-effect model. We also explored possible sources of heterogeneity among the studies by using meta-regression analysis. Results suggest that the time interval between patient's admission to bedside TLS examination was closely related to TLS accuracy. CONCLUSION: This meta-analysis demonstrated that detecting ULCs is a convenient bedside tool and has high accuracy for early AHF diagnosis in ED. TLS could be recommended to be applied for early diagnosis of AHF in ED.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Ultrassonografia , Doença Aguda , Serviço Hospitalar de Emergência , Humanos
7.
Chin Med J (Engl) ; 131(8): 950-955, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29664056

RESUMO

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α-subunit (eIF2α)/CCAAT/enhancer-binding protein homologous protein (CHOP) endoplasmic reticulum (ER) stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin (0.1, 0.5, or 2.5 µmol/L) or DEVD-CHO (selective inhibitor of caspase-3, 100 µmol/L) for 1 h before the addition of ox-LDL (100 µg/ml) and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons using Tukey's tests. A value of P < 0.05 was considered statistically significant. RESULTS: Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis (31.9% vs. 4.9%, P < 0.05). Simvastatin (0.1, 0.5, and 2.5 µmol/L) led to a suppression of ox-LDL-induced apoptosis (28.0%, 24.7%, and 13.8%, F = 15.039, all P < 0.05, compared with control group). Ox-LDL significantly increased the expression of PERK (499.5%, P < 0.05) and phosphorylation of eIF2α (451.6%, P < 0.05), if both of which in the control groups were considered as 100%. Simvastatin treatment (0.1, 0.5, and 2.5 µmol/L) blunted ox-LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P < 0.05, compared with control group) and phosphorylation of eIF2α (407.8%, 339.1%, 187.5%, F = 11.430, all P < 0.05, compared with control group). In contrast, DEVD-CHO treatment had no significant effect on ox-LDL-induced expression of PERK (486.4%) and phosphorylation of eIF2α (418.8%). Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. CONCLUSIONS: This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacologia , Oligopeptídeos/farmacologia , Sinvastatina/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , Humanos
8.
J Crit Care ; 44: 424-429, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29353119

RESUMO

PURPOSE: We evaluated the diagnostic accuracy of PCT to distinguish between gram-negative (GN) and gram-positive (GP) bloodstream infections nosocomial pneumonia (NP) patients and compared PCT levels with the pneumonia severity index (PSI) for predicting mortality. METHODS: Data were collected retrospectively for blood culture-positive NP patients between January 2014 and August 2016. PCT levels were compared between patients with GN versus GP infections. Outcome variables included 28- and 60-day mortality. RESULTS: PCT level was higher in GN infections than in GP infections. PCT could differentiate between GN and GP infections with an AUC value of 0.706. At a PCT cutoff of 5.4 ng/mL, the specificity for GN infections were 80.3%. The AUCs for 28- and 60-day mortality were 0.758 and 0.759 for PSI, and 0.620 and 0.634 for PCT. Serum PCT level was less predictive of mortality in GN NP patients compared with that for GP NP patients. There was a significantly positive correlation between PCT and PSI, and the correlation in GP NP patients was better than that in GN NP patients. CONCLUSIONS: PCT could differentiate between GN and GP bloodstream infections in patients with NP. However, PCT levels were less predictive of mortality compared with the PSI.


Assuntos
Bacteriemia/microbiologia , Infecção Hospitalar/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Pneumonia Bacteriana/microbiologia , Pró-Calcitonina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Infecção Hospitalar/mortalidade , Feminino , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Positivas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Arch Pharm Res ; 40(10): 1176-1185, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28840536

RESUMO

Sepsis is a systemic inflammatory response syndrome caused by severe infections. Astilbin is a dihydroflavonol derivative found in many medicinal and food plants with multiple pharmacological functions. To investigate the effects of astilbin on sepsis-induced acute lung injury (ALI), cecal ligation and puncture was performed on rats to establish a sepsis-induced ALI model; these rats were then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration were determined to evaluate the effects of astilbin on sepsis-induced ALI. We found that astilbin treatment significantly attenuates sepsis-induced lung injury and improves survival rate, lung injury scores, lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration. Astilbin treatment also dramatically decreased the production of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression and production of macrophage inhibitory factor (MIF), which inhibits the inflammatory response. Collectively, these data suggest that astilbin has a protective effect against sepsis-induced ALI by inhibiting MIF-mediated inflammatory responses. This study provides a molecular basis for astilbin as a new medical treatment for sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Flavonóis/uso terapêutico , Oxirredutases Intramoleculares/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/metabolismo , Modelos Animais de Doenças , Oxirredutases Intramoleculares/sangue , Pulmão/imunologia , Pulmão/patologia , Fatores Inibidores da Migração de Macrófagos/sangue , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Masculino , Ratos Sprague-Dawley , Sepse/complicações , Sepse/imunologia , Análise de Sobrevida
10.
Am J Emerg Med ; 35(4): 579-583, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27979420

RESUMO

OBJECTIVE: The aim of this study was to evaluate procalcitonin (PCT) diagnostic accuracy in discriminating gram-negative (GN) from gram-positive (GP) bloodstream infections and determining the relationship between PCT levels, infection sites, and pathogen types. METHODS: Clinical and laboratory data were collected from patients with blood culture (BC)-positive sepsis between January 2014 and December 2015. PCT levels at different infection sites were compared, as was the presence of GN and GP bloodstream infection. A receiver operating characteristic (ROC) curve was generated to assess diagnostic accuracy. RESULTS: Of the 486 monomicrobial BCs, 254 (52.26%) were positive for GN bacteria (GNB), and 202 (42.18%) for GP bacteria (GPB). Median PCT levels were higher in BCs positive for GN (2.42ng/ml, IQR: 0.38-15.52) than in those positive for GPB (0.49ng/ml, IQR: 0.13-5.89) (P<0.001). In the ROC analysis to differentiate between GNB and GPB, the area under the curve was 0.628 (95% CI: 0.576-0.679). When the cutoffs for PCT were 10.335 and 15.000ng/ml, the specificity of GNB infection was 80.2% and 84.2%, respectively. PCT levels caused by GNB differed between Escherichia coli and Acinetobacter baumanni/Burkholderia cepacia, Klebsiella pneumonia and Acinetobacter baumanni. PCT levels caused by GPB differed between Staphylococcus epidermidis/Staphylococcus aureus and Staphylococcus hominis/Staphylococcus haemolyticus, Enterococcus faecium and Enterococcus faecalis/S.hominis/S. haemolyticus. Among patients with known infection sites, there were statistical differences in PCT levels between abdominal infection and pneumonia/infective endocarditis, urinary tract infection and pneumonia/catheter-related infection/infective endocarditis. CONCLUSION: PCT can distinguish between GNB and GPB infection, as well as between different bacterial species and infection sites.


Assuntos
Bacteriemia/sangue , Calcitonina/sangue , Infecções Relacionadas a Cateter/sangue , Endocardite Bacteriana/sangue , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Positivas/sangue , Pneumonia Bacteriana/sangue , Infecções Urinárias/sangue , Infecções por Acinetobacter/sangue , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Biomarcadores/sangue , Infecções por Burkholderia/sangue , Infecções por Burkholderia/microbiologia , Burkholderia cepacia , Infecções Relacionadas a Cateter/microbiologia , Serviço Hospitalar de Emergência , Endocardite Bacteriana/microbiologia , Enterococcus faecalis , Enterococcus faecium , Escherichia coli , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Unidades de Terapia Intensiva , Infecções por Klebsiella/sangue , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Estudos Retrospectivos , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Staphylococcus epidermidis , Staphylococcus haemolyticus , Staphylococcus hominis , Infecções Urinárias/microbiologia
11.
Biomed Environ Sci ; 29(12): 868-876, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28081747

RESUMO

OBJECTIVE: PERK/eIF2α/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/eIF2α/CHOP signaling pathway in vascular endothelial cells. METHODS: The effects of ox-LDL on PERK and p-eIF2α protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective eIF2α phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. RESULTS: Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of eIF2α phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective eIF2α phosphatase inhibitor, salubrinal. CONCLUSION: This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/eIF2α/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Lipoproteínas LDL/metabolismo , Transdução de Sinais , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo , Fator de Iniciação 2 em Eucariotos/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL/genética , Fator de Transcrição CHOP/genética , eIF-2 Quinase/genética
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