RESUMEN
Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. More and more studies have reported that mitochondrial-related genes (MTRGs) were associated with the clinical outcomes of multiple tumors solely. In this study, we aimed to develop a novel prognostic model based on MTRGs. Differentially expressed MTRGs were identified from TCGA-LUAD and GSE31210 cohorts. Univariate Cox regression analysis was utilized to screen differentially expressed MTRGs that were related to prognosis of LUAD. Then, LASSO Cox regression analysis was used to develop a prognostic signature. ESTIMATE was used for estimating the fractions of immune cell types. In this study, we identified 44 overlapping differentially expressed MTRGs in TCGA-LUAD and GSE31210 cohorts. Among 44 overlapping differentially expressed MTRGs, nine genes were associated with prognosis of LUAD. When the penalty parameter lambda was the minimum, there were six genes meeting the conditions of constructing the signature, including SERPINB5, CCNB1, FGR MAOB, SH3BP5, and CYP24A1. The survival analysis suggested that prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. Cox regression analyses showed that the risk score was an independent predictor of LUAD prognosis. As with the results of ESTIMATE score, the degree of immune cell infiltration in the low-risk group was higher than that in the high-risk group, such as TIL, Treg, and B cells. In addition, TMB and cancer stem cell infiltration were higher in the low-risk group than the high-risk group. In conclusion, we developed a novel MTRG signature acting as a negative independent prognostic factor. In the future, individualized treatments and medical decision-making may benefit from using the predicted model.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Pronóstico , Análisis de Supervivencia , Microambiente Tumoral/genéticaRESUMEN
OBJECTIVE: The aim of this qualitative study was to explore the challenges that patients with epilepsy (PWEs) face and the opportunities or areas where changes in nursing care may improve epilepsy care in western China. METHODS: Semi-structured interviews with open-ended questions based on a review of the literature were conducted at the epilepsy center of a tertiary hospital in western China. A total of 18 PWEs, 18 caregivers and 11 neurology nurses were interviewed by using purposive sampling. The data were transcribed verbatim, and a content analysis was used to conduct the framework analysis. RESULTS: Three key themes were identified, namely, the impact of epilepsy, barriers to epilepsy management, and measures in nursing care for improving epilepsy care. Psychological stress, the side effects of drugs and accidental injury related to seizures were reported to be the main negative impacts on patients. Limited knowledge about epilepsy, poor adherence to therapy, and a lack of effective communication between patients and medical staff were the major barriers to epilepsy management. Strengthening health education, assessing the frequency and type of seizures, screening for psychological disorders and mental intervention, and maintaining continuity of care were identified as crucial measures for nurses to improve epilepsy care. CONCLUSIONS: This study highlights the challenges among PWEs and opportunities for improving the quality of epilepsy care in western China. Limited knowledge and poor drug adherence are the main barriers to epilepsy management, which might be improved by more health education and continuing care provided by nurses. Assessing seizures, screening for psychological disorders and providing appropriate psychological care would help improve epilepsy care.
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Epilepsia , Cuidadores/psicología , Epilepsia/psicología , Epilepsia/terapia , Humanos , Cumplimiento de la Medicación , Investigación Cualitativa , Estrés PsicológicoRESUMEN
BACKGROUND: Endothelial dysfunction may play a key role in non-obstructive coronary artery atherosclerosis. Our study aimed to evaluate the vascular endothelial function and its influencing factors in patients with non-obstructive coronary artery atherosclerosis. METHODS: A total of 131 consecutive patients with non-obstructive coronary artery atherosclerosis were enrolled. Flow-mediated dilatation (FMD) was measured at baseline and 1-year follow-up. Endothelial progenitor cells (EPCs) were counted by staining the fasting venous blood with antibodies against CD34 and vascular endothelial growth factor receptor 2. RESULTS: Systolic blood pressure, pulse pressure and the levels of HbA1c in participants with baseline FMD < 6% (n = 65) were significantly higher than those with baseline FMD ≥ 6% (n = 66). Baseline FMD was negatively associated with EPC counts (r = - 0.199, P < 0.05) and systolic blood pressure (r = - 0.315, P < 0.01). The 1-year FMD was significantly increased compared to the baseline FMD [(9.31 ± 5.62) % vs (7.31 ± 5.26) %, P < 0.001]. Independent predictors of FMD improvement included elevated EPC counts (OR = 1.104, 95% CI: 1.047-1.165, P < 0.001) and decreased levels of serum creatinine (OR = 0.915, 95% CI: 0.843-0.993, P = 0.034). CONCLUSIONS: Family history of premature cardiovascular diseases, hypertension, elevated systolic pressure, and HbA1c > 6.5% are independent risk factors for endothelial dysfunction in non-obstructive atherosclerotic patients. Elevated peripheral blood EPC counts and decreased levels of serum creatinine are independent predictors of endothelial function improvement.
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Arteria Braquial/fisiopatología , Enfermedad de la Arteria Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Vasodilatación , Anciano , Antígenos CD34/sangre , Biomarcadores/sangre , Presión Sanguínea , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Creatinina/sangre , Diabetes Mellitus/sangre , Células Progenitoras Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
Polysaccharide chromium (III) derivatives are gaining increasing attention in improving type 2 diabetes. In this study, the sulfated polysaccharide from Enteromorpha prolifera (SPE) with 4.8 kDa was prepared by specific enzymatic hydrolysis. The obtained SPE was used to prepare a rhamnan-type sulfated polysaccharide derivative (SPED). Results indicated that O-H, C=O, and S=O were effectively involved in the chelation of SPED (chromium content 20.26%). Acute (half lethal dose > 2.38 g/kg) and sub-acute toxicity showed that SPED had no damaging effects on mice. Anti-diabetic experiment demonstrated that SPED improved glucose metabolism. Moreover, SPED promoted the PI3K/PKB/GSK-3ß signaling pathway by regulating mRNA expression of insulin receptors (IR), insulin receptor substrate 2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB), and glycogen synthase kinase 3ß (GSK-3ß). In conclusion, the SPED might represent a novel marine-derived candidate against hyperglycemia, which may undergo further pharmaceutical development as a hypoglycemic agent.
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Desoxiazúcares/farmacología , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/farmacología , Mananos/farmacología , Polisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animales de Enfermedad , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hiperglucemia/metabolismo , Insulina/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Maternal nicotine (NIC) exposure causes overweight, hyperleptinemia and metabolic disorders in adult offspring. Our study aims to explore the underlying mechanism of perinatal NIC exposure increases obesity susceptibility in adult female rat offspring. In our model, we found that adult NIC-exposed females presented higher body weight and subcutaneous and visceral fat mass, as well as larger adipocytes, while no change was found in food intake. Serum profile showed a higher serum glucose, insulin and leptin levels in NIC-exposed females. In adipose tissue and liver, the leptin signaling pathway was blocked at 26 weeks, presented lower Janus tyrosine kinase 2 and signal transducer and activator of transcription 3 gene expression, higher suppressor of cytokine signaling 3 gene expression (in adipose tissue) and lower leptin receptors gene expression (in liver), indicating that peripheral leptin resistance occurred in NIC-exposed adult females. In female rats, the expression of lipolysis genes was affected dominantly in adipose tissue, but lipogenesis genes was affected in liver. Furthermore, the glucose and insulin tolerance tests showed a delayed glucose clearance and a higher area under the curve in NIC-exposed females. Therefore, perinatal NIC exposure programed female rats for adipocyte hypertrophy and obesity in adult life, through the leptin resistance in peripheral tissue.
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Leptina/metabolismo , Nicotina/toxicidad , Agonistas Nicotínicos/toxicidad , Obesidad/inducido químicamente , Obesidad/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/ultraestructura , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Grasa Intraabdominal/efectos de los fármacos , Lipólisis/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Embarazo , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To investigate the clinical manifestations and complications in the patients of anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis. METHODS: We retrospectively collected clinical data of 143 patients diagnosed with anti-NMDA receptor encephalitis. According to the complexity of clinical symptoms, the patients were divided into two groups: ≥4 clinical symptoms group (96 cases, 67.1%) and <4 group (47 cases, 32.9%). There were 109 patients with complications and 34 patients without any complicaitons, The related factors to symptom complexity and complications were analyzed by univariate and multivariate analysis method. RESULTS: In the 143 patients of anti-NMDA receptor encephalitis, 120 (83.9%) exhibited seizures, 130 (90.9%) presented with psychiatric symptoms. Pulmonary infections (58.7%) and gastrointestinal disorders (49.0%) were the most common complications. Univariate analysis showed that the complexity of clinical symptoms was related to abnormal electroencephalography (EEG), positive anti-NMDA receptor antibody in cerebrospinal fluid(CSF) and serum. There were more frequent seizures, disorders of consciousness, abnormal movements, central hypoventilation in the patients with complications than those in patients without complications, all the differences were signifcant (P<0.05). Multivariate analysis showed that abnormal EEG was an independent risk factor for symptom complexity ãodds ratio(OR)=2.620, P<0.05ã. The abnormal movements and the activities of daily living (ADL) on admission were predictor factors for the incidence of complications (OR=4.338, 0.980, respectively, P<0.05). CONCLUSIONS: In the patients of anti-NMDA receptor encephalitis, abnormal EEG may related to more complex clinical symptoms. Abnormal movements and low ADL on admission seems to be independent risk factors related to the incidence of complications.
RESUMEN
One sulphur-containing amide (N-[2-(4-Hydroxyphenyl)-ethyl]-3-methanesulfonyl-N-methyl-propionamide) which was isolated from Glycosmis lucida Wall ex Huang had a different NMR profile with this kind of compounds' normal case. Based on the information obtained by nuclear magnetic resonance pectroscopy (NMR) and mass spectrometry (MS), its configurations in solution were investigated. The results indicated that the compound would have two stable configurations in solution as the double bond switched between C-N and C-O in an appropriate rate. This phenomenon was clearly exposed by the one dimension selective NOE (1D-NOE) experiments. This conclusion would play an active role in the structure analysis work of this kind of compounds.
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Rutaceae/química , Amidas/química , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas , Estructura Molecular , Sulfonamidas/química , Azufre/químicaRESUMEN
A screening of Chinese medicinal herbs and wild plants for agrochemicals was carried out; the essential oil of Glycosmis lucida leaves was found to possess significant repellent activity against Tribolium castaneum and Liposcelis bostrychophila. It was found that the main components included elixene (19.81%), spathulenol (10.68%), anethole (12.05%), verbenone (10.32%) followed by ß-caryophyllene (6.87%). The essential oil, anethole and verbenone were strongly repellent against T. castaneum (96, 86 and 94%, respectively, at 15.73 nL cm-2) and L. bostrychophila (100, 68 and 72%, respectively, at 31.58 nL cm-2) after a 2h treatment. The results indicate that anethole and verbenone had the potential to be developed as natural repellents for control of stored product insects.
Asunto(s)
Repelentes de Insectos/farmacología , Aceites Volátiles/farmacología , Rutaceae/química , Derivados de Alilbenceno , Animales , Anisoles/farmacología , Aceites Volátiles/análisis , TriboliumRESUMEN
BACKGROUND: Hypothermia when cardiopulmonary resuscitation begins may help achieve defibrillation and return of spontaneous circulation (ROSC), but few data are available. OBJECTIVE: The objective of this study was to determine whether prearrest hypothermia improved defibrillation and cardiac function in a rabbit ventricular fibrillation (VF) model. RESULTS: Thirty-six New Zealand rabbits were randomized equally to receive normothermia (Norm) (~39°C), post-ROSC hypothermia (~33°C), or prearrest hypothermia (~33°C). Ventricular fibrillation was induced by alternating current. After 4 minutes of VF, rabbits were defibrillated and given cardiopulmonary resuscitation until ROSC or no response (≥30 minutes). Hemodynamics and electrocardiogram were monitored; N-terminal pro-brain natriuretic peptideand troponin I were determined by enzyme-linked immunosorbent assay. Myocardial histology and echocardiographic data were evaluated. First-shock achievement of perfusion rhythm was more frequent in prearrest than normothermic animals (7/12 vs 1/12; P=.027). After ROSC, dp/dtmax was higher in prearrest than normothermic animals (P<.001). Left ventricular end-systolic pressure was higher in prearrest than normothermic animals (P=.001). At 240 minutes after ROSC, troponin I and N-terminal pro-brain natriuretic peptide were lower in prearrest than normothermic animals (15.74±2.26 vs 25.09±1.85 ng/mL and 426±23 vs 284±45 pg/mL, respectively), the left ventricular ejection fraction and cardiac output were lower in the Norm group than other 2 groups (P<.01). Myocardial histology was more disturbed in normothermic than post-ROSC and prearrest animals, but was not different in the latter 2 groups. CONCLUSIONS: Induction of hypothermia before VF led to improved cardiac function in a rabbit VF model through improving achievement of perfusing rhythm by first-shock defibrillation and facilitating resuscitation.
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Reanimación Cardiopulmonar/métodos , Cardioversión Eléctrica , Paro Cardíaco/terapia , Hipotermia Inducida , Miocardio/patología , Fibrilación Ventricular , Animales , Modelos Animales de Enfermedad , Corazón/fisiología , Paro Cardíaco/complicaciones , Paro Cardíaco/fisiopatología , Masculino , Miocardio/ultraestructura , Conejos , Factores de TiempoRESUMEN
During our screening program for agrochemicals from Chinese medicinal herbs and wild plants, the essential oils of Evodia calcicola and Evodia trichotoma leaves were found to possess strong repellency against the red flour beetle Tribolium castaneum adults, the cigarette beetle Lasioderma serricorne adults and the booklouse Liposcelis bostrychophila. The two essential oils obtained by hydrodistillation were investigated by GC-MS. The main components of E. calcicola essential oil were identified to be (-)-ß-pinene (44.02%), ß-phellandrene (20.93%), ocimene (16.49%), and D-limonene (9.87%). While the main components of the essential oil of E. trichotoma were D-limonene (69.55%), 1R-a-pinene (11.48%), caryophyllene (2.80%) and spathulenol (2.24%). Data showed that T. castaneum was the most sensitive than other two stored product insects. Compared with the positive control, DEET (N, N-diethyl-3- methylbenzamide), the two essential oils showed the same level repellency against the red flour beetle. However, the essential oil of E. trichotoma showed the same level repellency against the cigarette beetle, while E. calcicola essential oil possessed the less level repellency against L. serricorne, relative to the positive control, DEET. Moreover, the two crude oils also exhibited strong repellency against L. bostrychophila, but lesser level repellency than the positive control, DEET. Thus, the essential oils of E. calcicola and E. trichotoma may be potential to be developed as a new natural repellent in the control of stored product insects.
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Escarabajos/efectos de los fármacos , Evodia/química , Repelentes de Insectos , Insecticidas , Aceites Volátiles/farmacología , Phthiraptera/efectos de los fármacos , Hojas de la Planta/química , Tribolium/efectos de los fármacos , Animales , Destilación/métodos , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificaciónRESUMEN
The aim of this research was to determine the chemical composition and insecticidal and repellent activity of the essential oil of Artemisia rupestris L. aerial parts against the booklice Liposcelis bostrychophila Badonnel and isolation of insecticidal and repellent constituents from the essential oil. The essential oil of A. rupestris was obtained by hydrodistillation and analyzed by GC-MS. A total of 30 components of the essential oil of A. rupestris was identified and the principal compounds in the essential oil were α-terpinyl acetate (37.18%), spathulenol (10.65%), α-terpineol (10.09%), and linalool (7.56%), followed by 4-terpineol (3.92%) and patchoulol (3.05%). Based on bioactivity-guided fractionation, the four active constituents were isolated from the essential oil and identified as α-terpineol, α-terpinyl acetate, 4-terpineol and linalool. The essential oil of A. rupestris exhibited contact toxicity against L. bostrychophila with LD50 value of 414.48 µg/cm². α-Terpinyl acetate (LD50 = 92.59 µg/cm²) exhibited stronger contact toxicity against booklice than α-terpineol (LD50 = 140.30 µg/cm²), 4-terpineol (LD50 = 211.35 µg/cm²), and linalool (LD550 = 393.16 µg/cm²). The essential oil of A. rupestris (LC50 = 6.67 mg/L air) also possessed fumigant toxicity against L. bostrychophila while the four constituents, 4-terpineol, α-terpineol, α-terpinyl acetate and linalool had LC50 values of 0.34, 1.12, 1.26 and 1.96 mg/L air, respectively. α-Terpinol and α-terpinyl acetate showed strong repellency against L. bostrychophila, while linalool and 4-terpinol exhibited weak repellency. The results indicate that the essential oil of A. rupestris aerial parts and its constituent compounds have potential for development into natural insecticides or fumigants as well as repellents for control of insects in stored grains.
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Artemisia/química , Repelentes de Insectos/farmacología , Insectos/efectos de los fármacos , Insecticidas/farmacología , Aceites Volátiles/farmacología , Componentes Aéreos de las Plantas/química , Aceites de Plantas/farmacología , Animales , Destilación , Repelentes de Insectos/química , Repelentes de Insectos/aislamiento & purificación , Insecticidas/química , Insecticidas/aislamiento & purificación , Dosificación Letal Mediana , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Control de Plagas , Aceites de Plantas/química , Aceites de Plantas/aislamiento & purificaciónRESUMEN
OBJECTIVE: To statistically analyze the clinical data from patients with multiple organ dysfunction syndrome in the elderly (MODSE), and to investigate the distribution pattern of traditional Chinese medicine (TCM) syndromes. METHODS: TCM data of 200 patients with MODSE was collected on 1, 3 and 7 days after diagnosis. Using 134 symptoms as observation indexes, clustering analysis was used to analyze the TCM symptoms and syndromes of these patients. RESULTS: In accordance with Diagnostic efficacy of standard TCM Syndrome, Diagnostics of TCM, State Standard of the People's Republic of China: clinical diagnose and treat Terminology of TCM, expert group differentiate on the professional knowledge and clinical manifestation and 7 types of TCM syndrome were selected. Among all syndrome types, there were 134 (22.3%) cases of phlegm stagnation with the largest population, 113 cases (18.8%) of toxic heat flourishing, 97 cases (16.2%) of damp-heat accumulation, 85 cases (14.2%) of qi-deficiency, 67 cases (11.2%) of both yin and yang deficiency, 55 cases (9.2%) of fu being filled and substances could not pass through, and 48 cases (8.1%) of qi stagnation and blood stasis. CONCLUSIONS: This preliminary study found 7 primary types of TCM syndrome in patients with MODSE, including syndrome of phlegm stagnation, toxic heat flourishing, accumulation of damp-heat, qi-deficiency, both yin and yang deficiency, fu being filled and substances could not pass through and qi stagnation and blood stasis. The most common syndrome is phlegm stagnation and deficiency, phlegm, blood stasis, toxic are the main etiology and pathology of the disease.
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Medicina Tradicional China , Insuficiencia Multiorgánica/diagnóstico , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Diagnóstico Diferencial , Femenino , Humanos , MasculinoRESUMEN
AIMS: The aim of this study was to investigate the precise role of hypoxia-induced autophagy in endothelial cells, and whether it contributes to the distinctive progression of infantile haemangioma (IH). METHODS AND RESULTS: The endothelial cells (EOMA and HUVECs) were cultured under hypoxic conditions for indicated times (0-72 h). The results showed that short exposure of the endothelial cells to hypoxia resulted in increased cell survival and proliferation, accompanied by occurrence of autophagy. Prolonged hypoxia-induced autophagy, correlating with increased cell death, was also detected afterwards. Correspondingly, autophagy inhibition prevented the enhanced cell survival and proliferation capacity, advanced the occurrence of cell-death in early hypoxic stage, and meanwhile attenuated the ability of prolonged hypoxia in cell-death induction. Moreover, our data demonstrated that the functional transformation of hypoxia-induced autophagy, pro-survival to pro-death, was rigorously regulated by the switch between hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) pathways. Importantly, we also revealed the activation levels of HIF-1α and mTOR, as well as the autophagy status during the progression of IH. CONCLUSION: This study unmasks the functional switch between HIF-1α and mTOR in regulating hypoxia-induced autophagy in endothelial cells and, more importantly, indicates its potential role in the progression of IH.
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Autofagia , Células Endoteliales/patología , Hemangioma/patología , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína 5 Relacionada con la Autofagia , Beclina-1 , Estudios de Casos y Controles , Hipoxia de la Célula , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Progresión de la Enfermedad , Células Endoteliales/metabolismo , Hemangioma/genética , Hemangioma/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , TransfecciónRESUMEN
OBJECTIVE: To investigate the activated protein C (APC) on the von Willebrand factor antigen (vWFAg) and von Willebrand factor cleaving protease (ADAMTS-13) protein expression in rat aortic endothelial cells (RAECs) induced by lipopolysaccharide (LPS). METHODS: RAECs from Wistar rats were cultured with the tissue explants adherence method. RAECs were cultured for one week, After one week culture, RAECs in 4-5 generations were divided into control group, LPS stimulation groups (1 mg/L) and APC intervention groups (0.1, 1 and 10 mg/L APC was added after LPS stimulation). The supernatants were obtained at 12, 24, 48, and 72 hours after LPS stimulated to determine the vWFAg and protein of ADAMTS-13 expression by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: In the control group, RAECs expressed little vWFAg and protein of ADAMTS-13. With stimulation of LPS, the vWFAg was significantly increased at 12 hours, and reached the peak at 48 hours [(285.45±30.13)%], and the level of ADAMTS-13 (µg/L) was gradually decreased, and reached the nadir at 72 hours (13.32±2.37), there was significant difference compared with control group [vWFAg: (94.53±7.83)%, ADAMTS-13: 115.76±2.36, both P<0.01). The effects on vWFAg promoting and ADAMTS-13 inhibition after LPS stimulation could be dose-dependently reversed by APC. 10 mg/L of APC could decrease the peak of vWFAg at 48 hours of LPS stimulation [(198.43±17.92)% vs. (285.45±30.13)%], and increase the minimize of ADAMTS-13 (µg/L) at 72 hours of LPS stimulation (125.25±2.70 vs. 13.32±2.37), with significant difference (both P<0.01). CONCLUSIONS: After stimulation with LPS, the level of vWFAg was time-dependent increased, as the protein of ADAMTS-13 was decreased. APC could attenuate the effect of LPS on vWFAg and protein of ADAMTS-13 with dose-dependent and time-dependent patterns.
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Proteínas ADAM/metabolismo , Células Endoteliales/efectos de los fármacos , Proteína C/farmacología , Proteína ADAMTS13 , Animales , Aorta/citología , Células Cultivadas , Células Endoteliales/metabolismo , Lipopolisacáridos/efectos adversos , Masculino , Ratas , Ratas Wistar , Factor de von Willebrand/metabolismoRESUMEN
OBJECTIVE: To investigate the possibility of adipose-derived mesenchymal stem cells (ADSC) in the treatment of type 1 diabetes (T1D). METHODS: ADSC were isolated from the adipotic tissue of abdomen in Sprague-Dawley rats (4-6 week-old,female) and expanded in vitro. Cells were then identified by testing their phenotypes through flow cytometry. Balb/c mice (8 week-old, male) were divided into 3 groups: T1D group, ADSC group and control group. Streptozocin (50 mg/kg·d) were injected intraperitoneally into mice of T1D group and ADSC group for 5 consecutive days to establish the T1D model. In ADSC group, ADSC were injected intravenously on day 3 of STZ injection. In control group, only PBS was injected. Fasting blood glucose (FGB) level was examined once a week. At the end of the 4th week, animals were killed. The pathological changes of islet were showed by histochemistry through hematoxylin-eosin staining (HE staining). ß cell insulin expression was detected by quantum dots immunofluorescence histochemistry. RESULTS: After ADSC administration, FGB levels decreased significantly from the second week. Whereas FGB levels in T1D group increased significantly and continuously during the experimental period. Moreover, ADSC effectively suppressed pancreatic islet damage induced by STZ and increased the expression of insulin protein in pancreatic ß cells. CONCLUSIONS: Intravenuously injected ADSC can prevent STZ induced ß-cell destruction and decrease blood glucose level.
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Tejido Adiposo/citología , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/cirugía , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Páncreas/patología , Animales , Glucemia/análisis , Separación Celular , Diabetes Mellitus Tipo 1/inducido químicamente , Femenino , Células Secretoras de Insulina/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
OBJECTIVE: To examine the impact of mild hypothermia on cardiac function, myocardial tissue integrity, and 48 hours mortality in a rabbits model of ventricular fibrillation after restoration of spontaneous circulation (ROSC). METHODS: The rabbits were randomly divided into four groups: normothermic post ROSC (NTPR, n = 10), mild hypothermia post ROSC (HTPR, n = 10), normothermic control (NTC, n = 8) and mild hypothermia control (HTC, n = 8). Ventricular fibrillation was induced by trans-epicardium electric-shook with alternating current in all the animals and ROSC was achieved through administration of adrenaline (i.v.) and artificial ventilation in group NTPR and HTPR. The body temperature of the animals was kept either at (39.0 ± 0.5) centigrade (NTPR and NTC) or (33.5 ± 0.5) centigrade (HTPR and HTC) for 4 hours after surgery for hemodynamic index data collection 0.5, 1, 2, 3 and 4 hours after surgery, 48 hours later, the mortality in the animals was recorded, and myocardial tissue samples were collected from survived animals for morphological examination by light and electric microscopy and analysis of apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. The content of ATP, ADP and AMP in the tissue samples was measured by high performance liquid chromatography (HPLC) for the calculation of energy charges (EC). RESULTS: (1)Hemodynamic indexes: as compared to the NTC group, HTC group exhibited significantly lower levels of heart rate (HR) and -dp/dt max in all the time points. No significant difference between the two groups in the levels of +dp/dt max and mean artery pressure (MAP) was found in all the time points but 0.5 hour. There was no significant difference in the levels of left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP), and femoral artery blood pressure between the two groups.(2) In comparison with NTPR group, HTPR group exhibited significantly (all P < 0.05) lower levels of HR (bpm) and -dp/dt max in all time points (ROSC 0.5, 1, 2, 3, 4 hours: HR 216.5 ± 33.3 vs. 292.9 ± 38.4, 218.2 ± 28.0 vs. 294.3 ± 37.0, 227.5 ± 25.4 vs. 291.4 ± 25.3, 232.4 ± 27.4 vs. 278.1 ± 30.8, 230.6 ± 22.0 vs. 285.1 ± 38.2; -dp/dt max 1847.1 ± 241.2 vs. 2383.3 ± 470.9, 1860.7 ± 167.8 vs. 2154.6 ± 319.5, 1822.3 ± 389.7 vs. 2239.7 ± 379.0, 1950.6 ± 412.9 vs. 2229.6 ± 392.4, 1875.7 ± 555.6 vs. 2396.7 ± 420.1). There was no significant difference between the two groups in the levels of LVEDP, +dp/dt max, LVESP, and femoral artery blood pressure. (3)Optical and electron microscopy revealed myocardium injury in samples from animals underwent ROSC. However, in comparison with the NTPR group, samples from HTPR group exhibited less damage to the myocardium structure. (4) Apoptosis index (AI) of myocardium was significantly (P < 0.05) higher in NTPR group (42.02%) than in HTPR group (26.39%). (5) Tests of myocardial energy: ATP level (µmol/g) in HTPR was significantly (P < 0.05) higher than NTPR (0.97 ± 0.26 vs. 0.65 ± 0.16). EC in NTPR was significant lower than it in two control groups [(0.33 ± 0.13)% vs. (0.52 ± 0.12)%, (0.55 ± 0.06)%, both P < 0.05], whereas no such difference was found between HTPR [(0.41 ± 0.12)%] and two control groups. (6) 48 hours survival rate in HTPR group was significantly higher (P = 0.043) as compared to NTPR group (100% vs. 60%). CONCLUSIONS: Myocardial dysfunction and myocardium tissue injury both develop in post-resuscitation rabbits with ventricular fibrillation. In these animals, reducing body temperature to the level of mild hypothermia after ROSC may improve the 48 hours survival rate, probably via mechanisms that suppress myocardial cell apoptosis. In our study, such intervention produced no obvious negative impact neither on the cardiac function nor hemodynamics.
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Hipotermia Inducida , Miocardio/patología , Resucitación , Fibrilación Ventricular/patología , Fibrilación Ventricular/fisiopatología , Animales , Masculino , ConejosRESUMEN
OBJECTIVE: To investigate the dose response effect and time response effect of lipopolysaccharide(LPS) on von Willebrand factor cleaving protease (ADAMTS-13, Vwf-cp) mRNA expression and protein in rat aortic endothelial cells (RAECs). METHODS: RAECs were grown by culturing of aortic tissue. When ARECs were cultured for one week, it was co-cultured by 1:3 to reach 4-5 generations. ARECs were randomly divided into five groups: control group and four LPS stimulation groups (0.01, 0.1, 1 and 5 µg/ml) . The RAECs and supernatants were obtained at 12, 24, 48, and 72 hours after being stimulated by LPS. ADAMTS-13 mRNA expression of RAECs was assessed by quantitation reverse transcription-polymerase chain reaction (RT-PCR), and protein of ADAMTS-13 in supernatants was determined by enzyme linked immunoadsorbent assay (ELISA). RESULTS: In the control group RAECs were shown to express ADAMTS-13 at both protein and mRNA levels. With the increase of concentration of LPS, or increase in stimulus duration, expression of ADAMTS-13 mRNA and protein were gradually lowered. Compared with the control group (25.22 ±1.41), the level of ADAMTS-13 mRNA in 0.01 µg/ml LPS stimulation group was markedly decreased at 48 hours (18.78±0.86, P<0.01). At 24 hours, the levels of ADAMTS-13 mRNA (23.43±0.63, 22.41±0.76) were markedly decreased in 0.1 µg/ml and 1 µg/ml LPS stimulation groups (P<0.05 and P<0.01). The level of ADAMTS-13 mRNA (20.01±2.47) in 5 µg/ml LPS stimulation group was markedly decreased at 12 hours (P<0.01). Compared with the control group [(115.76±2.36) ng/ml], protein level of ADAMTS-13 [(113.43±1.07) ng/ml] was markedly decreased at 12 hours in 0.01 µg/ml LPS stimulation group (P<0.05). The protein level of ADAMTS-13 [(7.63±2.64) ng/ml] was lowest in 5 µg/ml LPS stimulation group at 72 hours (P<0.01). CONCLUSION: Normal RAECs can express ADAMTS-13 at both mRNA and protein to certain extent. The expression of ADAMTS-13 mRNA and protein are decreased after LPS challenge in different concentrations for different duration in dose dependent and time dependent manner.
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Proteínas ADAM/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Lipopolisacáridos/farmacología , Proteína ADAMTS13 , Animales , Aorta/citología , Células Cultivadas , Endotelio Vascular/citología , Masculino , Ratas , Ratas WistarRESUMEN
Inflammatory responses are an important element in the atherosclerotic process. Therefore, inflammatory markers can potentially serve as predictors of cardiovascular risk. However, the existing data are limited and controversial. We conducted a prospective cohort study with 263 patients with first acute ST-segment elevation myocardial infarction (STEMI) who were admitted to our Hospital within 6 h after the symptoms onset. Clinical data were recorded and serum admission levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble P-selectin (sP-selectin) were determined. The patients were then followed up for 3 years to document cardiovascular mortality. During the follow-up, 34 patients died from cardiovascular causes. The admission levels of IL-6 were significantly higher in these patients, whereas sICAM-1, sVCAM-1, and sP-selectin were comparable between these and the survived patients. The Kaplan-Meier plots revealed a significant increase in cardiovascular mortality with increasing levels of IL-6 (P = 0.0002, χ(2) test). The logistic regression analysis indicated that IL-6 was an independent predictor for cardiovascular mortality. To conclude, our findings indicate that elevated admission levels of IL-6, but not soluble adhesion molecules, provide valuable information for risk assessment of long-term cardiovascular mortality in patients with STEMI.