RESUMEN
Objective: This study aimed to elucidate the prognostic significance of serum soluble thrombomodulin (sTM), lung ultrasound score (LUS), and lactate levels in patients with extrapulmonary acute respiratory distress syndrome (ARDS), with the goal of refining mortality risk prediction in this cohort. Methods: In a prospective cohort of 95 patients with extrapulmonary ARDS admitted to the intensive care unit, we investigated the primary endpoint of 28-day mortality. Utilizing Lasso-Cox regression analysis, we identified independent prognostic factors for mortality. A predictive nomogram was developed incorporating these factors, and its performance was validated through several statistical measures, including the consistency index, calibration plot, internal validation curve, decision curve analysis, interventions avoided analysis, receiver operating characteristic curve analysis, and Kaplan-Meier survival analysis. We further conducted a subgroup analysis to examine the impact of prone positioning on patient outcomes. Results: The study identified baseline serum sTM, LUS, and lactate levels as independent predictors of 28-day mortality in extrapulmonary ARDS patients. The predictive nomogram demonstrated superior prognostic accuracy compared to the use of sTM, LUS, or lactate levels alone, and outperformed traditional prognostic tools such as the Acute Physiology and Chronic Health Evaluation II score and the partial pressure of arterial oxygen to fractional inspired oxygen ratio. The subgroup analysis did not show a significant impact of prone positioning on the predictive value of the identified biomarkers. Conclusion: Our study results support the development and validation of a novel prognostic nomogram that integrates key clinical biomarkers and ultrasound imaging scores to predict mortality in patients with extrapulmonary ARDS. While our research is preliminary, further studies and validation are required.
RESUMEN
The etiology of intervertebral disc degeneration (IDD) and osteoarthritis (OA) is complex and multifactorial. Both predisposing genes and environmental factors are involved in the pathogenesis of IDD and OA. Moreover, epigenetic modifications affect the development of IDD and OA. Dysregulated phenotypes of nucleus pulposus (NP) cells and OA chondrocytes, including apoptosis, extracellular matrix disruption, inflammation, and angiogenesis, are involved at all developmental stages of IDD and OA. RNA binding proteins (RBPs) have recently been recognized as essential post-transcriptional regulators of gene expression. RBPs are implicated in many cellular processes, such as proliferation, differentiation, and apoptosis. Recently, several RBPs have been reported to be associated with the pathogenesis of IDD and OA. This review briefly summarizes the current knowledge on the RNA-regulatory networks controlled by RBPs and their potential roles in the pathogenesis of IDD and OA. These initial findings support the idea that specific modulation of RBPs represents a promising approach for managing IDD and OA.
Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , MicroARNs , Núcleo Pulposo , Osteoartritis , Humanos , Degeneración del Disco Intervertebral/patología , Osteoartritis/metabolismo , Núcleo Pulposo/metabolismo , Diferenciación Celular , Matriz Extracelular/metabolismo , Apoptosis , Disco Intervertebral/metabolismo , MicroARNs/metabolismoRESUMEN
Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.
Asunto(s)
Medicamentos Herbarios Chinos , Sepsis , Masculino , Humanos , Persona de Mediana Edad , Femenino , Método Doble Ciego , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Medicamentos Herbarios Chinos/uso terapéutico , Puntuaciones en la Disfunción de ÓrganosRESUMEN
In this study, we aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 was used to screen the serums of 238 admitted hospital patients between February 6 and February 14, 2020 with confirmed or suspected SARS-CoV-2. SARS-CoV-2 RNA was detected on pharyngeal swab specimens using real time RT-PCR. 194 (81.5%) of the serums were detected to be antibody (IgM and/or IgG) positive, significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibodies between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85), whose nucleic acid tests were negative. The antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped from below 50% to over 80%. However, the positive rates of viral RNA maintained above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. Overall, the suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is key for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After the 11th day post-disease onset, the diagnosis for viral infection should be majorly dependent on serological assay.
Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Pacientes Internos , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Pruebas Serológicas , Adulto , Anciano , COVID-19 , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Pandemias , ARN Viral/sangre , SARS-CoV-2RESUMEN
The current study investigated the protective effects of inactivated pseudomonas aeruginosa (IPA) on myocardial ischemia reperfusion injury (MIR/I) and the mechanisms governing this interaction. Left anterior descending coronary artery ligation was performed on rats for 30 min and reperfusion was performed for a subsequent 2 h. Rat hearts were obtained and the myocardial infarction area was determined using nitroblue tetrazolium. Myocardial cell apoptosis was determined using flow cytometry. Malondialdehyde (MDA) content, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity and catalase (CAT) activities were assayed using the corresponding kits. Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were assayed using western blot and immunofluorescence analysis. When compared with the model group, the results of IPA treatment revealed improved heart function, reduced myocardial infarction area and reduced endothelial cell apoptosis, which led to decreased LDH and MDA levels, and increased SOD and CAT levels in serum, and decreased LDH and MDA levels and increased SOD and CAT in myocardial tissues. Moreover, increased Nrf2 and HO-1 expression levels in the myocardial tissues were also observed at all concentrations of IPA. It was concluded that IPA pretreatment ameliorated MIR/I and reduced endothelial apoptosis and oxidative stress via the Nrf2/HO-1 pathway.
RESUMEN
Dysregulation of microRNA36133p (miR36133p) was previously reported in endothelial cells (ECs) during heat stress. The aim of the present study was to investigate the precise role of miR36133p in heat stress. In the present study, potential gene targets of miR36133p in heattreated ECs were assessed, and the potential effects of miR36133p were determined using Gene Ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to identify signaling pathways that may be affected by miR36133p in heattreated cells. Reverse transcriptionquantitative PCR, western blotting and annexin VFITC/propidium iodide staining were performed to detect miRNA expression, protein expression and apoptosis, respectively. Luciferase gene reporter assay was performed to evaluate the association between miR36133p and mitogenactivated protein kinase kinase kinase 2 (MAP3K2). Bioinformatics analysis revealed 865 potential gene targets for miR36133p and a series of functions and pathways in heattreated ECs. 'Negative regulation of apoptotic process' was identified as a potential function of miR36133p. In addition, functional analysis confirmed the downregulated expression levels of miR36133p in ECs during heat stress, which was accompanied by an increase in apoptosis; restoration of miR36133p expression inhibited apoptosis. MAP3K2 protein was demonstrated to be upregulated in heattreated ECs, and overexpression of miR36133p reduced MAP3K2 expression levels. Additionally, MAP3K2 was targeted by miR36133p. These results indicated that miR36133p may have complicated roles in ECs under heat stress. miR36133p may serve an important role in the apoptosis of heattreated ECs, and this effect may be partly achieved by targeting MAP3K2.
Asunto(s)
Apoptosis/genética , Respuesta al Choque Térmico/genética , MAP Quinasa Quinasa Quinasa 2/genética , MicroARNs/genética , Proliferación Celular/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Regulación de la Expresión Génica/genética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Transducción de SeñalRESUMEN
OBJECTIVES: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, randomized, controlled study. SETTING: Thirty-three hospitals in China. PATIENTS: A total of 710 adults 18-75 years old with severe community-acquired pneumonia. INTERVENTIONS: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]). CONCLUSIONS: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Neumonía/tratamiento farmacológico , Adolescente , Adulto , Anciano , China , Infecciones Comunitarias Adquiridas , Método Doble Ciego , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neumonía/mortalidad , Estudios Prospectivos , Respiración Artificial/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
To investigate the regulation of endothelial cell (EC) microRNAs (miRNAs) altered by heat stress, miRNA microarrays and bioinformatics methods were used to determine changes in miRNA profiles and the pathophysiological characteristics of differentially expressed miRNAs. A total of 31 differentially expressed miRNAs were identified, including 20 downregulated and 11 upregulated miRNAs. Gene Ontology (GO) enrichment analysis revealed that the validated targets of the differentially expressed miRNAs were significantly enriched in gene transcription regulation. The pathways were also significantly enriched in the Kyoto Encyclopedia of Genes and Genomes analysis, and most were cancer-related, including the mitogen-activated protein kinase signaling pathway, pathways involved in cancer, the Wnt signaling pathway, the Hippo signaling pathway, proteoglycans involved in cancer and axon guidance. The miRNA-gene and miRNAGO network analyses revealed several hub miRNAs, genes and functions. Notably, miR3613-3p played a dominant role in both networks. MAP3K2, MGAT4A, TGFBR1, UBE2R2 and SMAD4 were most likely to be controlled by the altered miRNAs in the miRNA-gene network. The miRNAGO network analysis revealed significantly complicated associations between miRNAs and different functions, and that the significantly enriched functions targeted by the differentially expressed miRNAs were mostly involved in regulating gene transcription. The present study demonstrated that miRNAs are involved in the pathophysiology of heat-treated ECs. Understanding the functions of miRNAs may provide novel insights into the molecular mechanisms underlying the heatinduced pathophysiology of ECs.
Asunto(s)
Respuesta al Choque Térmico/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , MicroARNs/análisis , MicroARNs/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/genética , Respuesta al Choque Térmico/fisiología , Calor , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , MicroARNs/metabolismo , Transducción de Señal/genéticaRESUMEN
Severe heat stroke (HS) consists of extreme hyperthermia with thermoregulatory failure, leading to high morbidity and mortality. Liver injury is a complication of HS that is associated with inflammatory responses and Kupffer cells (KCs), which are resident macrophages in the liver that serve as a major source of inflammatory cytokines; however, the association and the underlying mechanisms of KC functions in HSinduced endotoxemia and inflammation require an improved understanding. The important chemokine macrophage inflammatory protein1α (MIP1α) increases inflammatory responses and the secretion of inflammatory molecules from KCs, including tumor necrosis factorα, interleukin (IL)1ß and IL6. In addition, the activation of cJun Nterminal kinase (JNK) signaling is responsible for the development of liver inflammation. Therefore, HS animal and cell models were constructed in order to investigate the pathways involved in the HSinduced dysfunction of KCs. The results of the present study suggest that JNK may be involved in the MIP1αassociated pathogenesis of KCs in HS injury.
Asunto(s)
Quimiocina CCL3/inmunología , Respuesta al Choque Térmico , Proteínas Quinasas JNK Activadas por Mitógenos/inmunología , Macrófagos del Hígado/inmunología , Transducción de Señal , Animales , Células Cultivadas , Inflamación/metabolismo , Interleucina-1beta/inmunología , Interleucina-6/inmunología , Macrófagos del Hígado/patología , Masculino , Ratas Wistar , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
The present study aimed to investigate whether magnesium isoglycyrrhizinate protects against renal ischemiareperfusion injury (RIRI), and to verify the underlying mechanisms. An RIRI rat model was induced by removing the right kidney, and exposing and clamping the left kidney. RIRI model rats were administered 30 mg/kg magnesium isoglycyrrhizinate for 3 days. Blood urea nitrogen (BUN) and serum creatinine levels in the blood of RIRI model rat were examined, compared with shamoperated controls. Magnesium isoglycyrrhizinate suppressed the activities of tumor necrosis factorα, interleukin (IL)1ß, IL6, superoxide dismutase, glutathione peroxidase, inducible nitric oxide synthase (iNOS) and caspase3 in RIRI model rats. Renal iNOS, matrix metalloproteinase (MMP)2, phosphorylatedsignal transducers and activators of transcription 3 (STAT3) and intercellular adhesion molecule1 (ICAM1) protein expression levels were suppressed by magnesium isoglycyrrhizinate treatment in RIRI model rats. These findings suggested that magnesium isoglycyrrhizinate protects RIRI via antiinflammatory, oxidative and apoptotic mechanisms in an RIRI rat model. These results implicate magnesium isoglycyrrhizinate pretreatment as a potential approach to protect against RIRI via suppression of the iNOS, ICAM1, MMP2 and STAT3 signaling pathways.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Isquemia/tratamiento farmacológico , Riñón/irrigación sanguínea , Sustancias Protectoras/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Saponinas/uso terapéutico , Triterpenos/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Nitrógeno de la Urea Sanguínea , Caspasa 3/metabolismo , Creatinina/metabolismo , Modelos Animales de Enfermedad , Glutatión Peroxidasa/sangre , Glutatión Peroxidasa/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Isquemia/sangre , Isquemia/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación/efectos de los fármacos , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Daño por Reperfusión/sangre , Daño por Reperfusión/patología , Factor de Transcripción STAT3/metabolismo , Saponinas/química , Saponinas/farmacología , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismo , Triterpenos/química , Triterpenos/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The aim of the present study was to investigate the effects of sodium tanshinone IIA sulfonate (STS) on inflammatory responses, aortic endothelial cell apoptosis, disseminated intravascular coagulation (DIC) and multiple organ damage in an animal model of classic heat stroke (CHS). The rats in the heat stroke (HS) and STStreated heat stroke (STSHS) groups were placed into a prewarmed animal temperature controller (ATC) at 35ËC. The moment at which the rectal temperature reached 43.5ËC was considered as the time of onset of HS. In the HS groups, the rats were removed from the ATC and allowed to recover at 26ËC for 0, 2, 6 or 12 h. In the STSHS groups, the rats received femoral vein injections of 540 mg/kg STS immediately following the onset of HS and were subsequently placed at a temperature of 26ËC to recover for 6 h. In the present study, the serum levels of tumor necrosis factor (TNF)α, interleukin (IL)1ß and IL6 were assessed using ELISA, and the numbers of apoptotic aortic endothelial cells were investigated using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nickend labeling combined with immunofluorescence. In the HS groups, the serum levels of TNFα, IL1ß and IL6, as well as the numbers of apoptotic aortic endothelial cells were increased compared with the normothermic control group. Additionally, the plasma prothrombin time, activated partial thromboplastin time and Ddimer level were significantly increased in the HS group compared with the normothermic control group following recovery for 6 h. By contrast, the platelet count was decreased in the HS group compared with the normothermic control group. The serum levels of creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase were increased and histopathological damage to multiple organs was observed in the HS group following recovery for 6 h. In the STSHS groups, cytokine levels and apoptotic aortic endothelial cell numbers were reduced compared with the HS group after 6 h recovery. STS (40 mg/kg) treatment additionally improved the serum levels of organ injury indicators and plasma indicators of coagulopathy, and prevented histopathological damage to multiple organs. These findings demonstrated that STS treatment may ameliorate multiple organ damage by attenuating inflammatory responses, aortic endothelial cell apoptosis and DIC in CHS. These results suggested that STS may hold potential as an alternative therapeutic strategy for the treatment of patients with HS.
Asunto(s)
Apoptosis/efectos de los fármacos , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/etiología , Células Endoteliales/efectos de los fármacos , Golpe de Calor/complicaciones , Golpe de Calor/patología , Fenantrenos/farmacología , Animales , Biomarcadores , Citocinas/sangre , Citocinas/metabolismo , Modelos Animales de Enfermedad , Coagulación Intravascular Diseminada/tratamiento farmacológico , Golpe de Calor/tratamiento farmacológico , Inflamación/patología , Masculino , RatasRESUMEN
BACKGROUND: High-sensitivity cardiac troponin is the most specific and sensitive biomarker of myocardial injury. However, no study has investigated whether the early concentration of high-sensitivity cardiac troponin is increased or is of value in predicting short-term prognosis in patients with type-A acute aortic dissection (AAD) in the emergency department. AIMS: To measure the high-sensitivity cardiac troponin T (hs-TnT) concentration in patients with type-A AAD upon hospital admission, and to assess its value in predicting short-term prognosis. METHODS: We enrolled consecutive patients with type-A AAD. Blood samples were collected on admission; hs-TnT concentrations were measured on the Elecsys 2010 system. High-sensitivity C-reactive protein (hs-CRP), D-dimer and other biochemical indicators were measured. Patients were divided into two groups according to hs-TnT concentration on admission (< or ≥0.014ng/mL). RESULTS: More than half (61.2%) of the 103 included patients had an hs-TnT concentration ≥0.014ng/mL. hs-TnT concentrations were significantly higher in those who died compared with survivors (0.292±0.516 vs. 0.069±0.154ng/mL; P=0.003). Multivariable Cox regression analysis suggested that hs-TnT is an independent factor for predicting in-hospital mortality risk (odds ratio: 2.202, 95% confidence interval: 1.111-4.367; P=0.024). Kaplan-Meier curves revealed a significant increase in hospital mortality in the hs-TnT(+) group compared with the hs-TnT(-) group (P=0.021). When hs-TnT was ≥0.042ng/mL, the sensitivity and specificity in predicting hospital short-term mortality were 70.8% and 76.4%, respectively. CONCLUSIONS: Our study suggests that hs-TnT concentration could be used as an early biomarker for the risk stratification of patients with type-A AAD in the emergency department; the relationship between hs-TnT concentration and long-term prognosis needs further investigation.
Asunto(s)
Aneurisma de la Aorta/sangre , Disección Aórtica/sangre , Biomarcadores/sangre , Troponina T/sangre , Enfermedad Aguda , Adulto , Anciano , Disección Aórtica/diagnóstico , Disección Aórtica/mortalidad , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/mortalidad , Distribución de Chi-Cuadrado , China , Servicio de Urgencia en Hospital , Femenino , Mortalidad Hospitalaria , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a critical regulator for cellular oxygen balance. Myocardial hypoxia can induce the increased expression of HIF-1α. Our goals were to evaluate the value of HIF-1α in predicting death of patients with acute decompensated heart failure (ADHF) and describe the in vivo relationship between serum HIF-1α and N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels. METHOD: We included 296 patients who were consecutively admitted to the emergency department for ADHF. The primary end point was in-hospital death. The patients were categorized as HFrEF (patients with reduced systolic function) and HFpEF (patients with preserved systolic function) groups. RESULTS: In our patients, the median admission HIF-1α level was 2.95 ± 0.85 ng/ml. The HIF-1α level was elevated significantly in HFrEF patients and deceased patients compared with HFpEF patients and patients who survived. The HIF-1α level was positively correlated with NT-proBNP and cardiac troponin T levels, and negatively correlated with left ventricular ejection fraction and systolic blood pressure. Kaplan-Meier curves revealed a significant increase in in-hospital mortality in ADHF patients with higher HIF-1α levels. Multivariable Cox regression analysis showed that HIF-1α levels were not correlated with the short-term prognosis of ADHF patients. CONCLUSIONS: This is the first study to evaluate the circulating levels of HIF-1α in ADHF patients. Serum HIF-1α levels may reflect a serious state in patients with ADHF. Due to the limitations of the study, serum HIF-1α levels were not correlated with the in-hospital mortality based on regression analysis. Further studies are needed to demonstrate the diagnostic and/or prognostic role of HIF-1α as a risk biomarker in patients with ADHF.
Asunto(s)
Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Mortalidad Hospitalaria/tendencias , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Admisión del Paciente/tendencias , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
miR-23b is a multifunctional microRNA that contributes to the regulation of multiple signaling pathways. It has been reported that miR-23b prevents multiple autoimmune diseases through the regulation of inflammatory cytokine pathways. In addition, the function and underlying mechanisms of miR-23b on sepsis are currently being investigated. In the present study, miR-23b inhibitor and mimics sequences were transfected into human vascular endothelial cells to inhibit and upregulate the expression of miR-23b, respectively. In addition, respective negative control (NC) sequences were transfected. The expression of miR-23b was found to be downregulated in the cells transfected with the mimics NC or inhibitor NC sequences following stimulation with lipopolysaccharide (LPS; P<0.01); however, higher expression levels were maintained in the cells transfected with the mimics sequence and very low levels were observed in the cells transfected with the inhibitor sequence. In addition, the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 were shown to increase following induction by LPS in the cells transfected with inhibitor/mimics NC sequences (P<0.05). However, the expression levels of these inflammatory factors decreased in the cells transfected with the mimics sequence, and increased to a greater degree in the cells transfected with the inhibitor sequence, as compared with the inhibitor NC sequences (P<0.05). Therefore, miR-23b may play a significant role in the pathogenesis and progression of sepsis by inhibiting the expression of inflammatory factors, including NF-κB, TNF-α, IL-6, ICAM-1, E-selectin and VCAM-1.
RESUMEN
The phase diagram of Ru-Ce-O was calculated by a combination of ab initio density functional theory and thermodynamic calculations. The phase diagram indicates that the solubility between ruthenium oxide and cerium oxide is very low at temperatures below 1100 K. Solid solution phases, if existing under normal experimental conditions, are metastable and subject to a quasi-spinodal decomposition to form a mixture of a Ru-rich rutile oxide phase and a Ce-rich fluorite oxide phase. To study the spinodal decomposition of Ru-Ce-O, Ru0.6Ce0.4O2 samples were prepared at 280 °C and 450 °C. XRD and in situ TEM characterization provide proof of the quasi-spinodal decomposition of Ru0.6Ce0.4O2. The present study provides a fundamental reference for the phase design of the Ru-Ce-O electro-catalyst.
RESUMEN
Embelin has been used to treat fever and inflammatory diseases for thousands of years. Although reports indicate that embelin has antiinflammatory effects, its effects on myocardial injury following cardiac arrest (CA) have not been previously explored. In this study, we aim to investigate the protective effects of embelin on myocardial ischemia-reperfusion injury (IRI) following CA in a rabbit model. Pro-inflammatory (TNF-α, IL-1ß, and IL-6) cytokines, cardiac troponin I (cTnI), necrosis ratio, apoptotic index (AI), hemodynamics, nuclear factor-kappa B (NF-κB) p65, and histological damage have been measured or evaluated. Embelin reverts TNF-α, IL-1ß, and IL-6 to basal levels and reduces the serum level of cTnI, the necrosis ratio, the AI, and the expression of NF-κB p65. Meanwhile, it improves the hemodynamics and myocardial function. Moreover, embelin-treated groups also showed improved myocardial morphology. Our results indicate that embelin may protect the heart against myocardial IRI following CA via its antiinflammatory abilities.
Asunto(s)
Antiinflamatorios/uso terapéutico , Benzoquinonas/uso terapéutico , Paro Cardíaco/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Presión Sanguínea/fisiología , Recuento de Eritrocitos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Recuento de Linfocitos , Masculino , Neutrófilos/citología , Recuento de Plaquetas , Conejos , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/antagonistas & inhibidores , Factor de Transcripción ReIA/metabolismo , Troponina I/sangre , Troponina I/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Gamma-glutamyl transpeptidase (GGT) is now considered to be one of the risk factors for cardiovascular disease. However, whether statins can alter GGT levels in arterial atheromatous plaque has not yet been studied. Therefore, the aim of this study is to determine whether statins can effectively decrease the expression of GGT in arterial atheromatous plaques. METHODS: We randomly divided 45 apolipoprotein E-knockout (ApoE KO) male mice into three groups: normal diet (ND) group,high-cholesterol diet (HCD) group and high-cholesterol diet and atorvastatin (HCD + Ato) group. We fed high-cholesterol food to the HCD and HCD + Ato group. After eight weeks, atorvastatin 5 mgâ¢kg-1â¢d-1 was given to HCD + Ato group mice. The serum GGT-1, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell-adhesion molecule-1 (VCAM-1) levels were measured at end of 16 weeks by using ELISA methods. The expressions of GGT-1, ICAM-1 and VCAM-1 in aorta were measured by RT-PCR and Western Blot. RESULTS: The ApoE KO mice with HCD were associated with a marked increase in plasma lipid, inflammatory factors, GGT-1, ICAM-1 and VCAM-1. The expressions of GGT-1, ICAM-1 and VCAM-1 in HCD aortic tissue were increased. At the HCD + Ato group were treated with atorvastatin, the levels of lipid, GGT-1, ICAM-1 and VCAM-1 were suppressed. Meanwhile, the expressions of GGT-1, ICAM-1 and VCAM-1 were significantly decreased in the whole aorta plaques. CONCLUSIONS: The effect of statins on the expression of GGT in aorta plaque was firstly observed in animal model. The research shows that statins can significantly decrease the expression of GGT in aortic atherosclerotic plaques.
Asunto(s)
Aorta/efectos de los fármacos , Enfermedades de la Aorta/tratamiento farmacológico , Apolipoproteínas E/deficiencia , Aterosclerosis/tratamiento farmacológico , Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Placa Aterosclerótica , Pirroles/farmacología , gamma-Glutamiltransferasa/metabolismo , Animales , Aorta/enzimología , Aorta/patología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Apolipoproteínas E/genética , Aterosclerosis/enzimología , Aterosclerosis/genética , Aterosclerosis/patología , Atorvastatina , Colesterol en la Dieta , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Regulación hacia Abajo , Mediadores de Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Factores de Tiempo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , gamma-Glutamiltransferasa/genéticaRESUMEN
BACKGROUND: Pseudomonas aeruginosa may cause severe or even fatal infection in hosts with immunodeficiency. Interleukin-17 (IL-17) is a newly discovered pro-inflammatory cytokine, which promotes the recruitment and activation of neutrophils in the respiratory tract by inducing release of chemokine C-X-C. OBJECTIVE: This study was conducted to explore the role of IL-17 in host defense against acute pseudomonas aeruginosa infection in lungs. METHODS: The expression of IL-17 and its downstream effectors (IL-1ß, MIP-2 and G-CSF) were detected in mouse lungs with acute pseudomonas aeruginosa infection; 48 h after intratracheal administration of justice plasmid, mice were infected with pseudomonas aeruginosa again, and the bacterial clearance rate and the expression of downstream effectors of IL-17, as well as the mice death rate, were determined 6 h later. RESULTS: The expression of IL-17 and its downstream effectors (IL-1ß, MIP-2 and G-CSF) significantly increased in mouse lungs with acute pseudomonas aeruginosa infection. After intratracheal administration of justice plasmid expressing IL-17, the expression of IL-17 and its downstream effectors significantly increased, accompanied by increase in neutrophil count. The justice plasmid expressing IL-17 was intratracheally administered before acute pseudomonas aeruginosa lung infection, which significantly increased the expression of IL-17 and its downstream effectors (IL-1ß, MIP-2 and G-CSF) in the respiratory tract, leading to increasing clearance rate of bacteria and survival rate. CONCLUSION: IL-17 may recruit neutrophil to the infected areas in the early phase of pseudomonas aeruginosa lung infection.
RESUMEN
To elucidate the biological functions of osteopontin (OPN) in gastric tumors and to better understand the molecular events of OPN responsible for the malignancy, the present studies were performed. Growth curve, apoptosis assay, invasion assay and migration assay revealed that OPN status significantly affected proliferation, apoptosis, invasion and migration in gastric cancer cell lines. In mouse xenograft models of human gastric cancer, OPN silencing significantly inhibited tumor growth and the incidence of metastasis compared with non-silenced control. Mechanistic investigations revealed that OPN silencing inhibited the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase (NF-κB) pathways, and OPN-mediated NF-κB activity was reduced in the presence of MAPK or PI3K inhibitor. Our findings also indicated that OPN through the NF-κB pathway promotes the expression of matrix metalloproteinase 2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (uPA), the activation of MMP-2 and MMP-9, and the inhibition of caspase-3. Taken together, our results reveal that OPN promotes the progression of gastric cancer through the NF-κB pathway, which is regulated by the MAPK and PI3K pathways and leads to MMP-2, MMP-9 and uPA activation and caspase-3 inhibition. These findings identify OPN as a novel oncogene in gastric cancer and suggest that OPN is an attractive therapeutic target for this aggressive malignancy.
Asunto(s)
Sistema de Señalización de MAP Quinasas , Metástasis de la Neoplasia/patología , Osteopontina/metabolismo , Neoplasias Gástricas/patología , Animales , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales , Osteopontina/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Interferencia de ARN , Neoplasias Gástricas/metabolismo , Quinasa de Factor Nuclear kappa BRESUMEN
BACKGROUND: Hypoxia-inducible factor 1 (HIF-1), a master regulator of oxygen homeostasis, is a heterodimer consisting of HIF-1α and HIF-1ß subunits, and is implicated in calcification of cartilage and vasculature. The goal of this study was to determine the relationship between serum HIF-1α with coronary artery calcification (CAC) in patients with type 2 diabetes. METHODS: The subjects were 405 (262 males, 143 females, age 51.3 ± 6.4 years) asymptomatic patients with type 2 diabetes mellitus. Serum HIF-1α and interleukin-6 (IL-6) levels were measured by ELISA. CAC scores were assessed by a 320-slice CT scanner. The subjects were divided into 4 quartiles depending on serum HIF-1α levels. RESULTS: Average serum HIF-1α was 184.4 ± 66.7 pg/ml. Among patients with higher CAC scores, HIF-1α levels were also significantly increased (p <0.001). HIF-1α levels positively correlated with CRP, IL-6, UKPDS risk score, HbA1c, FBG, and CACS, but did not correlate with diabetes duration, age, and LDL. According to the multivariate analysis, HIF-1α levels significantly and independently predict the presence of CAC. ROC curve analysis showed that the serum HIF-1α level can predict the extent of CAC, but the specificity was lower than the traditional risk factors UKPDS and HbA1c. CONCLUSION: As a marker of hypoxia, serum HIF-1α level may be an independent risk factor for the presence of CAC. These findings indicate that elevated serum HIF-1α may be involved in vascular calcification in patients with type 2 diabetes mellitus.