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PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.
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Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients.
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Enfermedad Crítica , Hipertensión Esencial , Antagonistas de los Receptores H2 de la Histamina , Humanos , Masculino , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Hipertensión Esencial/tratamiento farmacológico , Hipertensión Esencial/mortalidad , Anciano , Enfermedad Crítica/mortalidadRESUMEN
Background: Our previous study reported that histamine H2 receptor antagonists (H2RAs) exposure was associated with decreased mortality in critically ill patients with heart failure (HF) through the same pharmacological mechanism as ß-blockers. However, population-based clinical study directly comparing the efficacy of H2RAs and ß-blockers on mortality of HF patients are still lacking. This study aims to compare the association difference of H2RAs and ß-blockers on mortality in critically ill patients with HF using the Medical Information Mart for Intensive Care III database (MIMIC-III). Methods: Study population was divided into 4 groups: ß-blockers + H2RAs group, ß-blockers group, H2RAs group, and Non-ß-blockers + Non-H2RAs group. Kaplan-Meier curves and multivariable Cox regression models were employed to evaluate the differences of all-cause mortalities among the 4 groups. Propensity score matching (PSM) was used to increase comparability of four groups. Results: A total of 5593 patients were included. After PSM, multivariate analyses showed that patients in H2RAs group had close all-cause mortality with patients in ß-blockers group. Furthermore, 30-day, 1-year, 5-year and 10-year all-mortality of patients in ß-blockers + H2RAs group were significantly lower than those of patients in ß-blockers group, respectively (HR: 0.64, 95%CI: 0.50-0.82 for 30-day; HR: 0.80, 95%CI: 0.69-0.93 for 1-year mortality; HR: 0.83, 95%CI: 0.74-0.93 for 5-year mortality; and HR: 0.85, 95%CI: 0.76-0.94 for 10-year mortality, respectively). Conclusion: H2RAs exposure exhibited comparable all-cause mortality-decreasing effect as ß-blockers; and, furthermore, H2RAs and ß-blockers had additive or synergistic interactions to improve survival in critically ill patients with HF.
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BACKGROUND: Apical hypertrophic cardiomyopathy (AHCM) is a subtype of hypertrophic cardiomyopathy. Due to its location, the thickening of the left ventricular apex can be missed on echocardiography. Giant negative T waves (GNTs) in left-sided chest leads are the hallmark electrocardiogram (ECG) change of AHCM. CASE SUMMARY: The first patient was a 68-year-old woman complaining of recurrent chest tightness persisting for more than 3 years. The second was a 59-year-old man complaining of spasmodic chest tightness persisting for more than 2 years. The third was a 55-year-old woman complaining of recurrent chest pain persisting for 4 mo. In all three cases, GNTs were observed several years prior to apical cardiac hypertrophy after other causes of T-wave inversion were ruled out. CONCLUSION: Electrophysiological abnormalities of AHCM appear earlier than structural abnormalities, confirming the early predictive value of ECG for AHCM.
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Background: During the prevalence of coronavirus disease 2019 (COVID-19), little was known about the knowledge, attitudes, practices (KAP) about COVID-19 and psychological status of college students in minority areas. This study aimed to evaluate the KAP of college students in minority areas of China toward COVID-19 and to provide a scientific basis for health education and policy formulation. Methods: From October 28th to November 6th, 2021, a cross-sectional study was conducted with 5,272 college students to examine KAP and its effects on mental health. Results: Regarding COVID-19 knowledge, the overall awareness rate was 24.11% (1,271). Regarding health attitudes, most students had positive attitudes about COVID-19 prevention and control (94.95%), and females had higher positive attitudes than males (OR: 1.920; CI: 1.494-2.469). Regarding preventive behaviors, more than half of the students took preventive measures (53.48%), and freshmen had the highest health behavior scores. In terms of psychological status, there were fewer females with depression and stress than males. Conclusion: College students in minority areas have positive health attitudes; however, their knowledge of COVID-19 prevention and control is low. Moreover, their precautionary behaviors are insufficient, and they have many negative emotions.
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COVID-19 , Masculino , Femenino , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Estudiantes/psicología , China/epidemiología , Estado de SaludRESUMEN
Radiation-related nasopharyngeal necrosis (RRNN) is a rare and often fatal complication in patients with nasopharyngeal carcinoma (NPC). Currently, no standard treatments are recommended for RRNN. The effects of traditional conservative treatments are suboptimal, and surgery for RRNN cannot be performed by inexperienced doctors. In the present study, the use of Endostar in two patients with RRNN was evaluated. Two patients with RRNN were treated at the Department of Oncology, Panyu Central Hospital (Guangzhou, China). Endostar was administrated (15 mg/day from day 1 to day 7, every three weeks) intravenously for four and seven cycles in a male and a female patient, respectively. The effects of Endostar were assessed using magnetic resonance imaging (MRI) and a nasopharyngoscope. The symptoms of RRNN in both patients were relieved after treatment with Endostar. MRI and nasopharyngoscope analysis revealed that necrosis of the nasopharynx was substantially decreased and nasopharyngeal ulcers were healed. Endostar has the potential to be a novel, effective therapy for the treatment of patients with RRNN. However, clinical trials are required to confirm the results of the present study.
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BACKGROUND: Wellens syndrome is an electrocardiogram (ECG) pattern seen in high-risk patients with unstable angina pectoris. It is characterized by inverted or biphasic T-waves that change into positive or pseudo-normalized waves at precordial leads when the patient experiences an angina attack; however, the mechanism for this condition remains unclear. CASE SUMMARY: A 47-year-old male patient experienced repeated, unprovoked episodes of chest pain for > 20 d, with worsening during the previous day. On the day of admission, he experienced episodes of paroxysmal chest pain lasting more than 30 min, in addition to radiating pain to the left arm and exertional dyspnea. The patient presented to the emergency department with no chest pain or other discomfort at that time. ECG at presentation showed sinus tachycardia and T-wave changes, which were identified as Wellens syndrome when combined with previous ECG findings. ECGs and myocardial enzymology examinations were normal when angina was present, but the ECG showed inverted or biphasic T-waves when angina was absent. After percutaneous coronary intervention, the ECGs demonstrated inverted or biphasic T-waves in the anterior precordial leads on days 0, 1, and 2, but normal T-waves on day 3. The ECGs showed no subsequent ischemic ST-T-wave changes. CONCLUSION: The Wellens syndrome pseudo-normalized T-waves likely reflect development of unstable angina pectoris into the hyperacute phase of ST-segment elevation myocardial infarction.
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Grass carp (Ctenopharyngodon idellus) is one of the three most cultivated freshwater fish around the world, but it is mainly consumed afresh, so only a small part of them are processed into salted fish or snack food. This research was performed to prepare and screen antioxidant peptides from grass carp muscle to promote its high-value utilization. The parameters of double-enzyme two-step hydrolysis were optimized, the peptides with the highest ABTS.+ scavenging ability were enriched and identified by Sephadex G-25 and LC-Q-Orbitrap-MS/MS. The synergistic-antagonistic effect among identified peptides was also investigated. The optimized conditions were hydrolyzed with protamex (10,000 U/g) at pH 8.0, 50°C for 3 h, followed by hydrolysis with alcalase (6,000 U/g) at pH 9.0, 50 °C for 2 h, and the protein-liquid ratio was 4%. The hydrolysates were further fractionated to obtain five fractions, in which fraction 3 (F3) exhibited the strongest ABTS.+ and O 2 · - scavenging ability with the IC50 values of 0.11 and 0.47 mg/ml, respectively. Twelve novel antioxidant peptides were identified, in which VAGW possessed the highest activity (139.77 µmol GSH/g). Significantly synergistic effects were observed on the two and three peptides' combination among VAGW, APPAMW, LFGY, FYYGK, and LLLYK, while the C-terminal tryptophan (Trp) played an important role in the synergism. This study found that grass carp muscle hydrolysates can be potential natural antioxidants in functional products. The synergistic effects among peptides may provide a perspective for the combined application of peptides.
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Guavinoside B (GUB) is the main active substance in guava fruit and shows promising biological activities. In this study, the inhibitory activity and mechanism of GUB on α-glucosidase were studied by using spectroscopic techniques, kinetic analysis, and molecular docking. Results indicated that GUB possessed significant inhibition ability on α-glucosidase, which was about 10 times that of acarbose. The GUB was a mixed-type inhibitor, which suppressed the activity of α-glucosidase through a reversible process. Fluorescence analysis revealed that GUB quenched the fluorescence of α-glucosidase statically, the formation of GUB-α-glucosidase complex was a spontaneous and exothermic process, van der Waals forces, hydrogen bonding, and hydrophobic interaction were the predominant driving forces, only one single-binding site on α-glucosidase was involved in the binding process. GUB inserted into the hydrophobic pocket of α-glucosidase with 11 hydrogen bonds and two π-π stacking formed. The presence of GUB changed the microenvironment near the fluorescent amino acids of α-glucosidase, and the structure of α-glucosidase was slightly changed, eventually leading to the decrease of α-glucosidase activity. PRACTICAL APPLICATIONS: Diabetes mellitus (DM) is a worldwide chronic metabolic disease threatening human health seriously. Guava fruit is a popular fruit, and its extracts were reported to show many biological activities. GUB is the main benzophenone glycoside in guava fruits. However, the inhibitory activity and mechanism of its specific active compound GUB are still unclear. Studies have shown that GUB could reversibly inhibit the activity of α-glucosidase, and its inhibitory ability was about 10 times that of acarbose. The kinetics and mechanism of inhibition were revealed. These will facilitate the further research and application of guava fruit and GUB in functional and healthy foods against hyperglycinaemia or even DM.
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Psidium , alfa-Glucosidasas , Acarbosa/análisis , Frutas/química , Inhibidores de Glicósido Hidrolasas/química , Humanos , Cinética , Simulación del Acoplamiento Molecular , Psidium/metabolismo , Análisis Espectral , alfa-Glucosidasas/metabolismoRESUMEN
Emergency care is a critical area of medicine whose outcomes are influenced by the time, availability, and accuracy of contextual information. The success of critical or emergency care is determined by the quality and accuracy of the information received during the emergency call and the data collected during emergency transportation. The Internet of Things (IoT) consists of many smart devices and components that communicate via their connection to the Internet, which is used to collect data with sensors that obtain personal health parameters. In the past, most health measurement systems were based on a single dedicated orientation, and few systems had multiple devices on the same platform. In addition to traditional health measurement technologies, most such systems use centralized data transmission, which means that health measurement data have become the exclusive intellectual asset of the system developer. Therefore, this study develops an IoT-based message-broker system that is deployed and demonstrated for five health devices: blood oxygen, blood pressure, forehead temperature, body temperature, and body weight sensors. A central controller accessed by radio-frequency identification (RFID) collects clients' health profiles on the cloud platform. All collected data can be quickly shared, analyzed, and visualized, and the health devices can be changed, added to, and removed reliably when the requirements change. Additionally, following the message queuing telemetry transport (MQTT) protocol, all devices can communicate with each other and be integrated into a higher-level health measurement standard (such as blood pressure plus weight or body temperature plus blood oxygen). We implement a smart healthcare monitoring system (SHMS) and verify its reliability. We use MQTT to establish an open communication format that other organizations can follow to perform individual patient vital sign monitoring in potential applications. The robustness and flexibility of this research can be verified through the addition of other systems. Through this structure, more large-scale health detection devices can be integrated into the method proposed in this research in the future. Personal RFID or health insurance cards can be used for personal services or in medical institutions, and the data can easily be shared through the mechanism of this research. Such information sharing will enable the utilization of medical resources to be maximized.
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BACKGROUND/PURPOSE: Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. METHODS: Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case-control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015-2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. RESULTS: Most patients (41/44, 93.2%) infected by S. Panama were <5 years old (median, 1.3 years). The case-control study showed that 28 out of the 41 (68.3%) manifested as bacteremia, compared to S. Typhimurium (11.1%). Patients infected by S. Panama had longer durations of fever (P = 0.005) and hospitalization (P < 0.001). Genomic analyses split the isolates into three clades: two clones caused the outbreak, whereas another one accounted for the sporadic infections before 2015. Cellular experiments revealed that S. Panama and other iNTS serovars showed higher monolayer penetration and intracellular survival within macrophages, compared to S. Typhimurium. CONCLUSION: This study confirmed that S. Panama is a clinically invasive serovar. Different iNTS serovars express common virulence phenotypes, but they may acquire invasiveness through distinct expression or combinations of virulence genes.
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Infecciones por Salmonella , Salmonella enterica , Estudios de Casos y Controles , Preescolar , Brotes de Enfermedades , Genómica , Humanos , Infecciones por Salmonella/epidemiología , Salmonella enterica/genética , Serogrupo , Taiwán/epidemiologíaRESUMEN
The receptor-like kinase Suppressor of BIR1 (SOBIR1) binds various receptor-like proteins (RLPs) that perceive microbe-associated molecular patterns (MAMPs) at the plasma membrane, which is thought to activate plant pattern-triggered immunity (PTI) against pathogen invasion. Despite its potentially crucial role, how SOBIR1 transmits immune signaling to ultimately elicit PTI remains largely unresolved. Herein, we report that a Nicotiana benthamiana gene NbRLP1, like NbSOBIR1, was highly induced upon Phytophthora parasitica infection. Intriguingly, NbRLP1 is characterized as a receptor-like protein localizing to the endoplasmic reticulum (ER) membrane rather than the plasma membrane. Using bimolecular fluorescence complementation and affinity purification assays, we established that NbRLP1 is likely to associate with NbSOBIR1 through the contact between the ER and plasma membrane. We further found that NbSOBIR1 at the plasma membrane partitions into mobile microdomains that undergo frequent lateral movement and internalization. Remarkably, the dynamics of NbSOBIR1 microdomain is coupled to the remodeling of the cortical ER network. When NbSOBIR1 microdomains were induced by the P. parasitica MAMP ParA1, tobacco cells overexpressing NbRLP1 accelerated NbSOBIR1 internalization. Overexpressing NbRLP1 in tobacco further exaggerated the ParA1-induced necrosis. Together, these findings have prompted us to propose that ER and the ER-localized NbRLP1 may play a role in transmitting plant immune signals by regulating NbSOBIR1 internalization.
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BACKGROUND: Lung cancer is one kind of malignant tumor with a high risk for morbidity and mortality compared to other solid organ malignancies. Brain metastases occur in 30-55% of non-small cell lung cancer (NSCLC) patients. Prognosis of NSCLC patients with brain metastases is very poor. Our previous study showed that cell adhesion molecule 2 (CADM2) could regulate the development of brain metastasis in NSCLC cells. Therefore, the objective of the study is to evaluate the effect of CADM2 on the prognosis of NSCLC patients with brain metastases. METHODS: The expression of CADM2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in the tissue of the primary tumor. Patients were followed up and overall survival (OS) was calculated. The relationships between CADM2 and clinicopathological features were analyzed using the chi-square test. Kaplan-Meier analysis was carried out to demonstrate the influence of CADM2 on the OS of patients. Univariate and multivariate Cox analyses were used to determine the prognosis of NSCLC patients with brain metastases. RESULTS: A total of 139 NSCLC patients with brain metastases from the Affiliated Cancer Hospital & Institute of Guangzhou Medical University, treated between January 2015 and December 2017 were evaluated retrospectively. The expression level of CADM2 in patients ranged from 1 to 17.2677, with a median of 6.0772. Chi-square analysis showed that CADM2 gene expression level was not significantly associated with gender, age, tumor location, histological subtype, tumor T stage, extracranial metastasis, or smoking status. However, CADM2 expression was notably associated with risk for lymph node metastasis. The results of the Kaplan-Meier analysis showed that high expression [CADM2 messenger RNA (mRNA) ≥6.0772] of CADM2 was markedly associated with poor prognosis. Univariate and multivariate Cox analyses demonstrated that CADM2 was an independent risk factor for survival in NSCLC patients with brain metastases (P<0.05). CONCLUSIONS: CADM2 expression is up-regulated and closely associated with disease progression and poor prognosis in NSCLC patients with brain metastases. CADM2 expression warrants special consideration given its potential prognostic significance that might help inform clinical decision making.
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Accumulation of filamentous aggregates of α-synuclein (AS) in Lewy bodies and neurites is characteristic of neurodegenerative diseases such as Parkinson's disease. Inhibition of AS fibrillation is helpful for understanding of AS aggregate structure and for developing chemical therapies. Herein, we report that the PtII -containing antitumor drug cisplatin suppresses filamentous aggregation of AS in solution. PtII thus contrasts strongly with reported transition-metal ions such as MnII , FeIII , and CuII , which accelerate AS aggregation. Interaction between PtII and the side chains of methionine and histidine residues was essential for inhibition of AS fibrillation. Binding of PtII to AS did not change the protein's overall random coil structure, as indicated by solution-state two-dimensional NMR and circular dichroism spectroscopy; and a solution of the ASâ PtII complex remained free of filamentous aggregates. Our results constitute interesting new information about the biological chemistry of metal ions in Parkinson's disease and might open new lines of research into the suppression of filamentous aggregation.
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Antineoplásicos/farmacología , Cisplatino/farmacología , Platino (Metal)/farmacología , alfa-Sinucleína/antagonistas & inhibidores , Antineoplásicos/química , Cisplatino/química , Platino (Metal)/química , Agregado de Proteínas/efectos de los fármacos , Soluciones , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMEN
OBJECTIVE: To study the pharmacognostical characteristics of stem and root of Berchemia floribunda for its further research and usage. METHODS: The plant was researched by macroscopic identification, microscopic identification and thin layer chromatography. RESULTS: The transverse section of B. floribunda root was eccentric. There were many fiber bundles in the secondary phloem and two different stone cells distributed in stem and root respectively. The results of TLC could identify the stem and root of B. floribunda. CONCLUSION: The microscopic characteristics of B. floribunda stem and root can be used as reference for its identification. Quercetin can be used as the characteristic component to identify the stem and root.
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Raíces de Plantas/anatomía & histología , Tallos de la Planta/anatomía & histología , Rhamnaceae/anatomía & histología , Antraquinonas/análisis , Cromatografía en Capa Delgada , Farmacognosia , Floema/anatomía & histología , Floema/química , Floema/citología , Raíces de Plantas/química , Raíces de Plantas/citología , Tallos de la Planta/química , Tallos de la Planta/citología , Polvos , Control de Calidad , Quercetina/análisis , Rhamnaceae/química , Rhamnaceae/citologíaRESUMEN
AIM OF THE STUDY: Artemisia vestita is a common traditional Tibetan medicinal plant which has been used widely in China for treating various inflammatory diseases. Since little is known about its active components, the purpose of this study was to isolate and identify the immunosuppressive compounds from Artemisia vestita. MATERIALS AND METHODS: A bioassay-guided isolation was performed with picryl chloride-induced contact hypersensitivity in mice. MTT assay and Flow cytometric analysis were used for determining Con A-induced lymphocyte proliferation and CD25 expression in T cells, respectively. RESULTS: The ethanol extract of the Artemisia vestita was found to possess significant inhibitory activity against the picryl chloride-induced contact hypersensitivity in mice. Then 4 fractions were isolated by macroporous adsorption resin and one of these fractions (AV3), which showed the highest activity in in vivo test, was further subjected to column chromatography. Nine known flavones were isolated and identified as pectolinarigenin (1), jaceosidin (2), cirsilineol (3), cirsimaritin (4), hispidulin (5), quercetin (6), 6-methoxytricin (7), acacetin (8), and apigenin (9). The structures of the 9 flavones were elucidated by spectral techniques. All the compounds were evaluated for their inhibitory activity on the proliferation and activation of T cells in vitro. Among the 9 flavones, cirsilineol (3), 6-methoxytricin (7) and apigenin (9) significantly inhibited T cell proliferation and activation in the bioassays. CONCLUSION: The result suggests that cirsilineol, 6-methoxytricin and apigenin are the major active components in Artemisia vestita.
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Artemisia/química , Flavonas/farmacología , Inmunosupresores/farmacología , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Proliferación Celular/efectos de los fármacos , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/inmunología , Femenino , Flavonas/aislamiento & purificación , Citometría de Flujo , Inmunosupresores/aislamiento & purificación , Medicina Tradicional Tibetana , Ratones , Ratones Endogámicos BALB C , Cloruro de Picrilo , Componentes Aéreos de las Plantas , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismoRESUMEN
Artemisia vestita Wall., a traditional Tibetan medicine, has wide clinical application for inflammatory diseases. However, its molecular mechanism of anti-inflammatory effect is poorly understood. In the present study, we investigated the anti-inflammatory activity and underlying mechanism of the ethanol extract from Artemisia vestita (AV-ext) on lipopolysaccharide (LPS)-induced sepsis. Pretreatment with AV-ext significantly decreased the levels of tumor necrosis factor-alpha (TNF-alpha) in serum and liver and lung tissues, and improved the survival of mice with experimental sepsis. AV-ext also remarkably reduced the expression levels of TNF-alpha, interleukin-1beta and cyclooxygenase-2 in LPS-stimulated RAW 264.7 macrophages and dose dependently suppressed the activation of mitogen-activated protein kinases (MAPKs), such as p38, extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Furthermore, pretreatment with AV-ext dose dependently inhibited the activation of nuclear factor-kappaB (NF-kappaB), as well as the degradation and phosphorylation of inhibitory kappaB (IkappaB) in LPS-activated RAW 264.7 macrophages. These results collectively reveal that AV-ext inhibits TNF-alpha release from macrophages by suppressing MAPK and NF-kappaB signaling pathways and suggest that AV-ext may be beneficial for the treatment of endotoxin shock or sepsis.