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OBJECTIVE: The objective of this study was to examine whether the National Institute of Health Stroke Scale was associated with the short- and long-term prognosis of patients with acute ischemic stroke treated with intravenous thrombolysis. METHODS: A total of 247 patients with acute ischemic stroke admitted to the hospital from April 2019 to October 2020 were retrospectively selected as study subjects, and the immediate and long-term prognosis after thrombolysis was assessed using the modified Rankin Scale and divided into good prognosis group (119 cases) and poor prognosis group (128 cases) based on the effect of thrombolysis. Both groups were treated with alteplase, the National Institute of Health Stroke Scale of the two groups was compared, and the factors affecting the prognosis of acute ischemic stroke were analyzed. RESULTS: After intravenous thrombolysis, 24 h, and 7 days of treatment, the National Institute of Health Stroke Scale in the poor prognosis group was higher than those of patients in the good prognosis group, and the differences were statistically significant (p<0.05). The results of the multivariate analysis suggested that National Institute of Health Stroke Scale before treatment was an independent factor associated with the 3-month (OR: 1.068, 95%CI 1.015-1.123, p=0.011) and long-term poor prognosis (OR: 1.064, 95%CI 1.012-1.119, p=0.015) in patients with acute ischemic stroke receiving intravenous thrombolysis after adjustment of age, gender, body mass index, smoking, alcohol consumer, onset-to-door time, door-to-needle time, and imaging score. CONCLUSION: The National Institute of Health Stroke Scale could be a promising indicator for the prognosis, and active intervention is needed to improve the quality of life in patients with acute ischemic stroke.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Calidad de Vida , Estudios Retrospectivos , Pronóstico , Terapia TrombolíticaRESUMEN
OBJECTIVE: The objective of this study was to examine whether the National Institute of Health Stroke Scale was associated with the short- and long-term prognosis of patients with acute ischemic stroke treated with intravenous thrombolysis. METHODS: A total of 247 patients with acute ischemic stroke admitted to the hospital from April 2019 to October 2020 were retrospectively selected as study subjects, and the immediate and long-term prognosis after thrombolysis was assessed using the modified Rankin Scale and divided into good prognosis group (119 cases) and poor prognosis group (128 cases) based on the effect of thrombolysis. Both groups were treated with alteplase, the National Institute of Health Stroke Scale of the two groups was compared, and the factors affecting the prognosis of acute ischemic stroke were analyzed. RESULTS: After intravenous thrombolysis, 24 h, and 7 days of treatment, the National Institute of Health Stroke Scale in the poor prognosis group was higher than those of patients in the good prognosis group, and the differences were statistically significant (p<0.05). The results of the multivariate analysis suggested that National Institute of Health Stroke Scale before treatment was an independent factor associated with the 3-month (OR: 1.068, 95%CI 1.015-1.123, p=0.011) and long-term poor prognosis (OR: 1.064, 95%CI 1.012-1.119, p=0.015) in patients with acute ischemic stroke receiving intravenous thrombolysis after adjustment of age, gender, body mass index, smoking, alcohol consumer, onset-to-door time, door-to-needle time, and imaging score. CONCLUSION: The National Institute of Health Stroke Scale could be a promising indicator for the prognosis, and active intervention is needed to improve the quality of life in patients with acute ischemic stroke.
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BACKGROUND: Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Our study aimed to investigate the prevalence of two conditions, angina and stroke, and relevant risk factors among older adults in six low- and middle- income countries(LMICs). METHODS: The data was from World Health Organization (WHO) Study on global AGEing and adult Health (SAGE) Wave 1 in China, Ghana, India, Mexico, Russian Federation and South Africa. Presence of CVD was based on self-report of angina and stroke. Multivariate logistic regression was performed to examine the relationship between CVD and selected variables, including age, sex, urban/rural setting, household wealth, and risk factors such as smoking, alcohol drinking, fruit/vegetable intake, physical activity and BMI. RESULTS: The age standardized prevalence of angina ranged from 9.5 % (South Africa) to 47.5 % (Russian Federation), and for stoke from 2.0% (India) to 6.1 % (Russia). Hypertension was associated with angina in China, India and Russian Federation after adjustment for age, sex, urban/rural setting, education and marital status (OR ranging from 1.3 [1.1-1.6] in India to 3.8 [2.9-5.0] in Russian Federation), furthermore it was a risk factor of stroke in five countries except Mexico. Low or moderate physical activity were also associated with angina in China, and were also strongly associated with stroke in all countries except Ghana and India. Obesity had a stronger association with angina in Russian Federation and China(ORs were 1.5[1.1-2.0] and 1.2 [1.0-1.5] respectively), and increased the risk of stroke in China. Smoking was associated with angina in India and South Africa(ORs were 1.6[1.0-2.4] and 2.1 [1.2-3.6] respectively ), and was also a risk factor of stroke in South Africa. We observed a stronger association between frequent heavy drinking and stroke in India. Household income was associated with reduced odds of angina in China, India and Russian Federation, however higher household income was a risk factor of angina in South Africa. CONCLUSION: While the specific mix of risk factors contribute to disease prevalence in different ways in these six countries - they should all be targeted in multi-sectoral efforts to reduce the high burden of CVD in today's society.
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Enfermedades Cardiovasculares/epidemiología , Países en Desarrollo/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Ghana/epidemiología , Humanos , India/epidemiología , Masculino , México/epidemiología , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Federación de Rusia/epidemiología , Sudáfrica/epidemiologíaRESUMEN
In the present study, pressure mediated microanalysis (PMMA), a fast, convenient and efficient capillary electrophoresis (CE) method was developed for studying enzyme kinetics of tyrosinase and inhibition kinetics of kojic acid, a model inhibitor of tyrosinase. The enzymatic reaction conditions and CE conditions were optimized in order to obtain high enzyme activity and short analysis time. By PMMA, only the product could be detected at 475 nm, and no voltage was applied to separate the product from the reaction mixture thus greatly simplifying the optimization procedure. The spectrophotometric assay and electrophoretically mediated microanalysis (EMMA) were also performed to validate the developed method. With the present method, the Michaelis-Menten constant (Km) was calculated to be 1.347 mM for tyrosinase. The inhibition constant of kojic acid to free tyrosinase (KI) and kojic acid to tyrosinase/L-DOPA complex (KIS) were calculated to be 36.64 and 74.35 µM, respectively, and the half-maximal inhibitory concentration (IC50) was determined to be 46.64 µM for kojic acid. The developed method is fast and convenient for studying enzyme kinetics, inhibition kinetics and further screening enzyme inhibitors.
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Evaluación Preclínica de Medicamentos/métodos , Electroforesis Capilar/métodos , Inhibidores Enzimáticos/farmacología , Monofenol Monooxigenasa/antagonistas & inhibidores , Presión , Pironas/farmacología , CinéticaRESUMEN
The agaricoglyceride is a new fungal secondary metabolite that constitutes esters of chlorinated 4-hydroxy benzoic acid and glycerol. The objective of this study was to explore whether the administration of agaricoglyceride could correct hepatic glycemic metabolism dysfunction by attenuating inflammation in the liver. The effects of agaricoglycerides on tumor necrosis factor-α, interleukin-1ß, vascular endothelial growth factor-α, interleukin-17, insulin secretion, adiponectin, leptin, hepatic glycogen, nuclear factor-κB activation, and total antioxidant activity were studied respectively. We demonstrated that administration of agaricoglycerides alleviated glycemic metabolism dysfunction, inflammation, and oxidative stress in mice. These data indicate that agaricoglyceride supplementation could restrain metabolic dysfunction through suppressing the nuclear factor-κB pathway as well as decreasing the levels of inflammatory cytokines and total antioxidant activities.
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Agaricus/química , Antiinflamatorios , Benzoatos/farmacología , Diabetes Mellitus/tratamiento farmacológico , Glicéridos/farmacología , Hígado/metabolismo , Adiponectina/sangre , Adiponectina/metabolismo , Animales , Benzoatos/química , Glucemia/efectos de los fármacos , Femenino , Glicéridos/química , Insulina/sangre , Insulina/metabolismo , Leptina/sangre , Leptina/metabolismo , Glucógeno Hepático/metabolismo , Ratones , Distribución AleatoriaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The heartwood of Caesalpinia sappan L. (Leguminosae), a widely used Chinese medicine in folk, has been used for the treatment of traumatic injury, stasis pain, amenorrhea, dysmenorrheal, as well as stabbing pain in the chest, abdomen and so on. Protosappanin B and brazilin, as the major bioactive homoisoflavones of Sappan Lignum, are used as the marker components for the quality control of the herb in China Pharmacopoeia. AIM OF THE STUDY: To establish a sensitive LC/MS/MS method for investigating the pharmacokinetic properties of protosappanin B and brazilin in rats after oral administration of Sappan Lignum extract, and compare their pharmacokinetics difference between normal and streptozotocin-treated rats. MATERIAL AND METHODS: A rapid, selective and sensitive LC/MS/MS method was developed and validated for the simultaneous quantification of protosappanin B and brazilin in rat plasma. Normal and streptozotocin-treated rats were orally administered with the Sappan Lignum extract at the same dose of 2.83 g extract/kg body weight (equivalent to 35.56 mg/kg of protosappanin B and 52.25 mg/kg of brazilin), respectively. RESULTS: After oral administration of Sappan Lignum extract, a remarkable increase (p<0.05) in the value of AUC0-24h, AUC0-∞, Cmax and T1/2 associated with protosappanin B and brazilin was observed in the streptozotocin-treated group. Compared with the normal rats, elimination of both compounds in the streptozotocin-treated rats was slower. CONCLUSION: The established method was successfully applied to compare the pharmacokinetic behaviors of protosappanin B and brazilin in rat plasma after oral administration of Sappan Lignum extract between normal and streptozotocin-treated groups; the results might suggest the accumulation of both compounds in diabetic pathologic states and the adverse reaction should be considered when it was used.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/farmacocinética , Isoflavonas/farmacología , Isoflavonas/farmacocinética , Animales , Área Bajo la Curva , Benzopiranos/química , Benzopiranos/farmacocinética , Benzopiranos/farmacología , Caesalpinia/química , Cromatografía Liquida/métodos , Diabetes Mellitus Experimental/sangre , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Fabaceae/metabolismo , Hipoglucemiantes/química , Isoflavonas/química , Masculino , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Extractos Vegetales/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Espectrometría de Masas en Tándem/métodosRESUMEN
The analysis of individual gene product should enable to clarify the role of a particular enzyme in a complex xylanase system of A. niger. The two genes encoding precursors of co-produced endo-1,4-¥â-D-xylanases, xynA1 and xynB, were isolated from Aspergillus niger SCTCC 400264 (SCTCC, China) by using RT-PCR technique and then successfully expressed in Escherichia coli BL21. The nucleotide sequences of the xynA1 and xynB genes revealed that they were only 52.5 percent homology to each other. Characterization of the recombinant enzymes revealed the different properties: the specific activity of recombinant XYNA1 was 16.58 U/mg compared to 1201.7 U/mg for recombinant XYNB; The optimum temperature and pH of the recombinant XYNA1 were 35 ¨¬C and 3.0, respectively, whereas the corresponding values for the recombinant XYNB were 55 ¨¬C and 5.0, respectively; The recombinant XYNB showed much more thermostability than recombinant XYNA1; The recombinant XYNB showed 94 percent of maximal activity after incubating in water for 60 min at 60 ¨¬C compared to no activity for recombinant XYNA1. Various metal ions had different effects on activity between the two recombinant xylanases.
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Aspergillus niger/aislamiento & purificación , Aspergillus niger/patogenicidad , Secuencia de Bases , Expresión Génica , Técnicas In Vitro , Reacción en Cadena de la Polimerasa , Xilanos/aislamiento & purificación , Activación Enzimática , Métodos , Métodos , VirulenciaRESUMEN
The analysis of individual gene product should enable to clarify the role of a particular enzyme in a complex xylanase system of A. niger. The two genes encoding precursors of co-produced endo-1,4-ß-D-xylanases, xynA1 and xynB, were isolated from Aspergillus niger SCTCC 400264 (SCTCC, China) by using RT-PCR technique and then successfully expressed in Escherichia coli BL21. The nucleotide sequences of the xynA1 and xynB genes revealed that they were only 52.5% homology to each other. Characterization of the recombinant enzymes revealed the different properties: the specific activity of recombinant XYNA1 was 16.58 U/mg compared to 1201.7 U/mg for recombinant XYNB; The optimum temperature and pH of the recombinant XYNA1 were 35 °C and 3.0, respectively, whereas the corresponding values for the recombinant XYNB were 55 °C and 5.0, respectively; The recombinant XYNB showed much more thermostability than recombinant XYNA1; The recombinant XYNB showed 94% of maximal activity after incubating in water for 60 min at 60 °C compared to no activity for recombinant XYNA1. Various metal ions had different effects on activity between the two recombinant xylanases.
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The analysis of individual gene product should enable to clarify the role of a particular enzyme in a complex xylanase system of A. niger. The two genes encoding precursors of co-produced endo-1,4--D-xylanases, xynA1 and xynB, were isolated from Aspergillus niger SCTCC 400264 (SCTCC, China) by using RT-PCR technique and then successfully expressed in Escherichia coli BL21. The nucleotide sequences of the xynA1 and xynB genes revealed that they were only 52.5% homology to each other. Characterization of the recombinant enzymes revealed the different properties: the specific activity of recombinant XYNA1 was 16.58 U/mg compared to 1201.7 U/mg for recombinant XYNB; The optimum temperature and pH of the recombinant XYNA1 were 35 ºC and 3.0, respectively, whereas the corresponding values for the recombinant XYNB were 55 ºC and 5.0, respectively; The recombinant XYNB showed much more thermostability than recombinant XYNA1; The recombinant XYNB showed 94% of maximal activity after incubating in water for 60 min at 60 ºC compared to no activity for recombinant XYNA1. Various metal ions had different effects on activity between the two recombinant xylanases.
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The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G(1) /S phase transition. The number of target cells was found to increase in phase G (0) /G (1) and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer.
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The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G1/S phase transition. The number of target cells was found to increase in phase G0/G1 and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer.
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As part of an ongoing program to explore the chemical constituents of Caribbean marine invertebrates, a family of 13 new diterpene glycosides, pseudopterosins P-Z (1-11) and seco-pseudopterosins H (12) and I (13), have been isolated from the organic extracts of two collections of the sea whip Pseudopterogorgia elisabethae procured near the Colombian Southwestern Caribbean Sea. The structures of compounds 1-13, including absolute stereochemistry, have been proposed on the basis of comprehensive spectral analyses, chemical transformations, specific rotation, and TLC chromatographic analyses. Pseudopterosin Q (2) inhibited thromboxane B2 (TXB2) (IC50 = 4.7 microM) and superoxide anion (O2-) (IC50 = 11.2 microM) generation from E. coli lipopolysaccharide (LPS) activated rat neonatal microglia in vitro. In contrast, pseudopterosins P (1), U (6), V (7), W (8), and X (9) as well as seco-pseudopterosins H (12) and I (13) demonstrated minimal effects on both TXB2 and O2- release. In addition, some of the new compounds displayed strong antituberculosis, antiviral, antimalarial, and anticancer activity.
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Antiinflamatorios no Esteroideos/aislamiento & purificación , Antimaláricos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Antituberculosos/aislamiento & purificación , Antivirales/aislamiento & purificación , Cnidarios/química , Diterpenos/aislamiento & purificación , Glicósidos/aislamiento & purificación , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antimaláricos/química , Antimaláricos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antituberculosos/química , Antituberculosos/farmacología , Antivirales/química , Antivirales/farmacología , Diterpenos/química , Diterpenos/farmacología , Glicósidos/química , Glicósidos/farmacología , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Océanos y Mares , RatasRESUMEN
The secondary metabolite composition of the gorgonian octocoral Eunicea pinta from San Andrés Island, Colombia, is described for the first time. This investigation has resulted in the isolation of eight new gamma-cembranolide-type diterpenes, namely, compounds 3-10, and a new saponin, 13, possessing a pregnene-derived aglycon. In addition, two previously known alpha-methylene-gamma-lactone cembranolides, euniolide (1) and succinolide (2), were also isolated. Their structures were determined on the basis of the results of spectroscopic analysis, X-ray diffraction analysis, and chemical conversions. The discovery of cembranolides 3-10 has prompted us to conclude that the structures proposed earlier for several uprolide-type cembranolides need revision and that a minor stereochemical correction is also in order for succinolide. Cytotoxicity of compounds 3, 4, and 13 toward various cancer cell lines and results of an antimycobacterial screening for 2, 4, and 13 also are described.