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High-intensity interval training (HIIT) has proven to be a time-saving and efficient exercise strategy. Compared with traditional aerobic exercise, it can provide similar or even better health benefits. In recent years, a number of studies have suggested that HIIT could be used as a potential exercise rehabilitation therapy to improve cognitive impairment caused by obesity, diabetes, stroke, dementia and other diseases. HIIT may be superior to regular aerobic exercise. This article reviews the recent research progress on HIIT with a focus on its beneficial effect on brain cognitive function and the underlying mechanisms. HIIT may become an effective exercise for the prevention and/or improvement of brain cognitive disorder.
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Humanos , Cognição , Exercício Físico , Treinamento Intervalado de Alta Intensidade , Obesidade , Acidente Vascular CerebralRESUMO
Purpose@#Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. @*Materials and Methods@#Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. @*Results@#Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. @*Conclusion@#The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.
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Indigenous knowledge and traditional culture for sustainable use of native plants in Juenang cultural region of Rangtang county, Aba Zang and Qiang Prefecture of Sichuan province, have been characterized in this paper followed the principles and methods of ethnobotany. The results indicate that 38 species from 27 families(including 6 species of fungi) are ethnobotanically used commonly in this area. Of 38 species of the native plants, 13 species from 12 families are collected for eatables and vegetables, 12 families and 16 species of indigenous plants for medicinal and edible use, 4 species from 4 families for decoration, 4 species from 4 families used for building materials or firewood, and 1 species from 1 families used for religious folklore. Under the influence of Juenang culture and Tibetan culture, indigenous knowledge such as instinctive reverence and gratitude for nature, protection ecological environment and habitats, and moderate use of natural resources(especially wild bioresource), have been gotten passed on from generation to generation in Juenang culture region of Rangtang county, which is of great significance to the protection of local bioresources and environment, including ethnic medicinal plants, and also to provide practical guidance for biodiversity conservation and ecological restoration in those alpine ecological vulnerable areas.
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Humanos , Biodiversidade , China , Conservação dos Recursos Naturais , Etnobotânica , Fungos/classificação , Conhecimento , Fitoterapia , Plantas Medicinais/classificaçãoRESUMO
The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1β, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1β, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.
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Animais , Masculino , Camundongos , Caspase 1 , Expressão Gênica , Hipocampo , Inflamassomos , Resistência à Insulina , Camundongos Endogâmicos C57BL , Quinases Relacionadas a NIMA , Proteína 3 que Contém Domínio de Pirina da Família NLR , Condicionamento Físico Animal , PiroptoseRESUMO
The spliceosome catalyzes nuclear pre-mRNA splicing via formation of an intron lariat and is arguably the most complex macromolecular machine in eukaryotic cells. Intron lariat formation is a conservative feature of the splicing reaction for both spliceosomal and group II introns. Despite the importance of the lariat formation in pre-mRNA splicing, an atomic-level understanding of the reaction mechanism remains elusive. In this work, a quantum mechanics and molecular mechanics method with thermodynamic integration is used to calculate the free-energy profile along the reaction pathway. The results demonstrate that the catalytic Mg2+ ion does not act as a Lewis acid to activate the nucleophile and the intron lariat is formed via a dissociative transition state stabilized by electrostatic interactions with two catalytic Mg2+ ions. Proton transfer occurs from the nucleophile to the leaving oxygen group through the phosphate substrate after the transition state is reached, which is important for stabilization of the intron-lariat product and the efficiency of pre-mRNA splicing. The two-metal-ion mechanism proposed in this study provides a novel insight into understanding of the splicing reaction catalyzed by the spliceosome.
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Biocatálise , Íntrons/genética , Modelos Moleculares , Teoria Quântica , Spliceossomos/metabolismo , Conformação Molecular , Spliceossomos/química , TermodinâmicaRESUMO
Methane (CH) is the simplest hydrocarbons and endogenous CHhas been thought only to be generated by methanogens in the oral cavity and gastrointestinal tract of the mammals. However, recent animal studies have shown that endogenous CHcan also be generated from choline and its metabolites in the mammals to protect the plasma membrane from reactive oxygen species attack and repair the membrane. In addition, exogenous CHcan ameliorate the oxidative stress injury of multiple tissues and organs through its anti-inflammatory, antioxidant and anti-apoptosis effects. This paper reviews the recent researches about CHsynthetic metabolism and biological functions, and highlights its potential of wide application in the prevention and treatment of oxidative stress related diseases and the significance for the development of gas medicine.
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Objective@#To explore the clinical effect of hydromorphone in the prevention of postoperative hyperpathia in patients receiving remifentanil combined anesthesia.@*Methods@#64 patients who were scheduled to receive abdominal surgery and postoperative analgesia were randomly divided into hydromorphone group(n=32) and control group (n=32) according to random number table.All the cases were given PCIA after surgery, the control group was given fentanyl 12.5μg/kg, and the hydromorphone group was given fentanyl 12.5μg/kg + hydromorphone 10μg/kg.The postoperative analgesic effects at different time, postoperative recovery, usage of PCIA and incidence of adverse effects in two groups were compared.@*Results@#There were no statistically significant differences in respiration recovery time, wake-up time, extubation time between the two groups (t=1.21, 0.83, 0.33, all P>0.05). The levels of MAP, HR after extubation of the hydromorphone group were significantly lower than those of the control group (t=2.84, 2.66, all P<0.05). The VAS scores at 30 min, 1h, 2h, 4h, 12h after operation in the hydromorphone group were significantly lower than those in the control group (t=8.83, 5.25, 8.77, 9.51, 9.69, all P<0.05), while the difference was not statistically significant between the two groups at 24h after operation (t=1.87, P>0.05). The press times and dosage of fentanyl during 1h, 24h after surgery of the hydromorphone group were significantly less than those of the control group(t=16.71, 36.38, 43.05, 10.98, all P<0.05). The adverse reactions between the two groups had no statistically statistical difference (χ2=0.14, P>0.05).@*Conclusion@#Postoperative analgesia of remifentanil combined anesthesia with hydromorphone can effectively prevent RIH, reduce other anesthetics dose, and does not increase the risk of complications.
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Objective To explore the application of ultrasound-guided femoral and sciatic nerve blocks combined with general anesthesia in lower limb fracture surgery.Methods Sixty four patients who received orthopaedics surgerywere randomly divided into two groups including combined group(n =32),control group (n =32).Control group was given general anesthesia alone,combined group was givengeneral anesthesia combined with ultrasound-guided femoral and sciatic nerve blocks.The intraoperative hemodynamic state at different time,anesthetic dosage,and agitation after waking upbetween two groups were compared.Results Compared with T1 moment,HR and MAP at T2 moment in both groups were significantly decreased (P < 0.05),while all these indicators at T3-T5 moment had no significant difference compared with the T1 moment in combined group (P > 0.05),while the difference was significant in control group (P < 0.05).Compared with control group,combined group had less intraoperative propofoland fentanyl dosage during the surgery,shorter awakening timeand extubation time,and the difference had statistical significance (P < 0.05).The incidence of agitation after waking up and degree of agitation was significantly decreased in combined group than that in control group (P < 0.05).Conclusion Ultrasound-guided nerve blockade combined with general anesthesia for lower limb fracture surgery,canmaintain the stability of intraoperative hemodynamics,reduce the dosage of analgesic drugs,and promote early awakening and extubation.
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Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future.
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We use quantum mechanical and molecular mechanical (QM/MM) simulations to study ATP hydrolysis catalyzed by the maltose transporter. This protein is a prototypical member of a large family that consists of ATP-binding cassette (ABC) transporters. The ABC proteins catalyze ATP hydrolysis to perform a variety of biological functions. Despite extensive research efforts, the precise molecular mechanism of ATP hydrolysis catalyzed by the ABC enzymes remains elusive. In this work, the reaction pathway for ATP hydrolysis in the maltose transporter is evaluated using a QM/MM implementation of the nudged elastic band method without presuming reaction coordinates. The potential of mean force along the reaction pathway is obtained with an activation free energy of 19.2 kcal/mol in agreement with experiments. The results demonstrate that the reaction proceeds via a dissociative-like pathway with a trigonal bipyramidal transition state in which the cleavage of the γ-phosphate P-O bond occurs and the O-H bond of the lytic water molecule is not yet broken. Our calculations clearly show that the Walker B glutamate as well as the switch histidine stabilizes the transition state via electrostatic interactions rather than serving as a catalytic base. The results are consistent with biochemical and structural experiments, providing novel insight into the molecular mechanism of ATP hydrolysis in the ABC proteins.
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Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Maltose/metabolismo , Transportadores de Cassetes de Ligação de ATP/química , Transporte Biológico , Escherichia coli/química , Proteínas de Escherichia coli/química , Hidrólise , Modelos Moleculares , TermodinâmicaRESUMO
<p><b>OBJECTIVE</b>To study subtype classification of gastric neuroendocrine neoplasm (NEN) and their clinicopathological characteristics in order to provide reference for clinical practice.</p><p><b>METHODS</b>Clinicopathological data of 241 gastric NEN patients (174 cases from China-Japan Friendship Hospital and 67 cases from The First Affiliated Hospital of Sun Yat-Sen University) between January 2011 and June 2016 were retrospectively summarized. According to serum gastrin, 24-hour intragastric pH monitoring and pathological grade, patients with gastric NEN were divided into 4 types: type I( (hypergastrinemia and achlorhydria, related to autoimmune chronic atrophic gastritis), type II( [hypergastrinemia and Zollinger-Ellison syndrome, related to gastrinoma or multiple endocrine neoplasia type I( (MEN-I()], type III( (sporadic disease with normal serum gastrin level), and type IIII( [poorly differentiated gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC)]. Clinicopathological features, treatment and prognosis of 4 types were analyzed.</p><p><b>RESULTS</b>Of 241 gastric NEN cases, there were 86 cases (35.7%) in type I(, 7 cases (2.9%) in type II(, 61 cases (25.3%) in type III( and 87 cases(36.1%) in type IIII(. Among 86 cases of type I( gastric NEN, 73 cases (84.9%) were multiple lesions,tumor size of 66 cases (76.7%) was less than 1 cm, all the 86 cases were polypoid or granular lesions. 2 cases(2.3%)presented distant metastasis, 69 cases (80.2%) had pathological grading as NET G1; most of them received endoscopic surgery treatment and follow-up; somatostatin analogs(SSA) was used in patients with multiple lesions and repeated recurrence after endoscopic treatment. Among 7 cases of type II(, 4 cases were gastrinoma, 3 cases MEN-I(; 5 cases presented distant metastasis; treatment included surgery, SSA and proton pump inhibitor (PPI) therapy. Among 61 cases of type III( gastric NEN, 49 cases(80.3%) were single lesion,tumor size of 25 cases(41.0%) was more than 2 cm, 29 cases(47.5%) had lymph node metastasis or distant metastasis; treatment included endoscopic resection, surgery or SSA therapy according to the tumor staging. Among 87 patients of type IIII( gastric NEN, 74 cases(85.0%) had single lesion,tumor size of 51 cases (58.6%) was more than 2 cm; lesions were found in gastric cardia in 35 cases (40.2%); 65 cases (74.7%) had lymph node metastasis or distant metastasis; treatment included chemotherapy, or surgery plus chemotherapy. At the end of follow-up(June 30, 2016), 58 patients were dead, including 1 case of type I(, 12 cases of type III( and 45 cases of type IIII(. The overall survival rate of all the patients was 74.2%, and was 98.8%, 100%, 79.3%, 39.2% of types I(, II(, III(, IIII( respectively. The overall survival rate between type III( and type IIII( gastric NEN was significantly different(P = 0.000).</p><p><b>CONCLUSIONS</b>Subtype classification of gastric NEN is very significant for making therapeutic decisions and prognostic evaluation. Patients of type I( or type II( gastric NEN have good prognosis,while those of type III( and type IIII( have poor prognosis, and those of type IIII( have the worst prognosis.</p>
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Adulto , Feminino , Humanos , Masculino , China , Metástase Linfática , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tumores Neuroendócrinos , Patologia , Terapêutica , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas , Patologia , Terapêutica , Taxa de SobrevidaRESUMO
Objective To investigate the clinical effect of modified storage type of autologous blood transfu-sion combined with shed blooding retransformation technique after OrthoPAT for artificial total knee arthroplasty. Methods 70 patients with total knee replacement were randomly divided into observation group and control group, 35 cases in each group.The observation group was treated with the modified storage autotransfusion combined shed blooding retransformation technique after OrthoPAT,while the control group was given conventional allogeneic blood transfusion.The hemoglobin values and blood coagulation function of the two groups at immediately before anesthesia and surgery,10min before autologous blood transfusion and after reinfusion of 15min,after 6h and 24h of surgery were recorded,and the drainage blood total value,allogeneic blood transfusion measurement issues and transfusion rate after 24h were recorded.Results The hemodynamics of the two groups were stable at each time,there were no difference at urine volume (all P >0.05).The coagulation conditions were normal of the two groups at each time,there were no statistically significant differences between the two groups (all P >0.05).The average volume and homologous blood transfusion rate in the observation group were (126.3 ±6.5)mL,1 /35,which were significantly lower than those in the control group [(476.4 ±10.6)mL,2 /35],the differences were statistically significant (t =10.73,χ2 =6.31,all P <0.05).The incidence rate of postoperative complication of the observation group was 5.7%,which was signifi-cantly lower than 22.9% of the control group,the difference between the two groups was statistically significant (χ2 =4.93,P <0.05).Conclusion The improved storage type of autologous blood transfusion combined with shed bloo-ding retransformation technique after OrthoPAT has exact effect for artificial total knee arthroplasty,the incidence of adverse reactions is low,as well as the low blood transfusion rate.
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Objective To study the effect of total knee arthroplasty after limb position on postoperative hemorrhage,to provide basis for clinical diagnosis and treatment.Methods 270 cases of total knee arthroplasty were selected.The patients were divided into groupⅠ,group Ⅱand group Ⅲ according to the random number table method, 90 cases in each group.Patients of group Ⅰ with limb hip and knee were straight,group Ⅱ hip joint elevation of 45 degrees,70 degrees of knee flexion,group Ⅲ hip joint elevation of 45 degrees,the knee extension.All the patients were intervened for 12h after operation,were placed drainage bag 24 hours.The lead flow,preoperative,postoperative hemoglobin and 5 days after the knee joint activity were compared in the three groups.Results Induced flow after surgery in group Ⅰ was (433.4 ±25.3)mL,which was significantly higher than (402.6 ±19.6)mL and (403.5 ± 21.5)mL in group Ⅱand group Ⅲ,and the differences were statistically significant (t =5.253,5.301,all P 0.05).The hemoglobin levels of the three groups were (92.3 ±4.2)g/L,(114.9 ±6.4)g/L and (113.2 ±7.5)g/L,which were significantly decreased after operation,the differences were statistically significant compared with before operation (t =5.083, 6.034,7.893,all P 0.05).There was no significant difference of range of motion in the three groups after 5 days of operation (P >0.05).Conclusion Hip flexion can effectively reduce bleeding after total knee arthro-plasty,the flexion and extension of knee joint had no significant effect on postoperative hemorrhage.
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Adenosine-5'-triphosphate (ATP) hydrolysis represents a most important reaction in biology. Despite extensive research efforts, the mechanism for ATP hydrolysis in aqueous solution still remains under debate. Previous theoretical studies often predefined reaction coordinates to characterize the mechanism for ATP hydrolysis in water with Mg(2+) by evaluating free energy profiles through these preassumed reaction paths. In the present work, a nudged elastic band method is applied to identify the minimum energy path calculated with a hybrid quantum mechanics and molecular mechanics approach. Along the reaction path, the free energy profile was obtained to have a single transition state and the activation energy of 32.5 kcal/mol. This transition state bears a four-centered structure that describes a concerted nature of the reaction. In the More-O'Ferrall-Jencks diagram, the results show that the reaction proceeds through a concerted path before the system reaches the transition state and along an associative path after the transition state. In addition, the calculated reaction free energy is -7.0 kcal/mol, in good agreement with experiment, capturing the exothermic feature of MgATP(2-) hydrolysis in aqueous solution, whereas the reaction was often shown to be endothermic in the previous theoretical studies. As Mg(2+) is required for ATP hydrolysis in cells, its role in the reaction is also elucidated.
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Trifosfato de Adenosina/química , Teoria Quântica , Água/química , Hidrólise , Magnésio/química , Modelos Moleculares , Conformação Molecular , Soluções , TermodinâmicaRESUMO
ATP-binding cassette (ABC) exporters pump various substrates across the cell membrane by alternating between inward-facing (IF) and outward-facing (OF) conformations of the transmembrane domains (TMDs). However, the structural determinants of the conformational transition and their functional roles are not fully understood. In this study, we carried out coarse-grained molecular dynamics (CG-MD) simulations with umbrella sampling for the multidrug transporter P-glycoprotein from Caenorhabditis elegans in the presence of the membrane and explicit water molecules. The potential of mean force (PMF) is obtained to identify a reliable pathway where the predicted OF and IF structures are in good agreement with available experiments. The CG-MD simulations reveal that the different transmembrane (TM) helices play distinct but highly cooperative roles in the large-scale conformational changes. Most notably, the CG-MD trajectories show that the periplasmic gate is closed before the cytoplasmic gate is opened during the OF to IF conformational transition in response to the dissociation of the nucleotide-binding domains (NBDs), capturing the unidirectional feature of substrate translocation through the exporter. The structural and dynamical analyses identify the structural determinants and their functional roles in the structural transition. The present work sheds light on how the mechanical force generated upon the NBD dissociation is transferred to the periplasmic end at a distance over 70 Å to close the gate, and subsequently to open the cytoplasmic gate. These results extend our understanding of the ABC transport mechanism.
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Transportadores de Cassetes de Ligação de ATP/química , Modelos Moleculares , Simulação de Dinâmica Molecular , Animais , Caenorhabditis elegans/química , Conformação ProteicaRESUMO
A new phenylpropanoid (1), together with seven known ones (2-8), has been isolated from the flowers of Rosa rugosa collected from Shanxi province by using various chromatographic techniques. Compound 1 is a new compound, and it displayed cytotoxicity against NB4, SH-SY5Y, PC3, A549 and MCF7 cell lines with IC₅₀ values of 8.2, 6.2, 4.3, 2.8, and 9.6 µmol · L⁻¹ respectively.
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Humanos , Linhagem Celular , Sobrevivência Celular , Medicamentos de Ervas Chinesas , Química , Farmacologia , Flores , Química , Estrutura Molecular , Álcool Feniletílico , Química , Farmacologia , Rosa , Química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
A phytochemical investigation on the stems of Garcinia bracteata collected from Xishuangbanna resulted in the isolation of a new flavone. By analysis of the HRESIMS, IR, UV, 1D and 2D NMR spectra, the structure of the new compound was determined as 7-methoxy-4',6-dihydroxy-8-isobutyryl-flavone(1). Compound 1 was also tested for its anti-tobacco mosaic virus(TMV) activity. Results suggested the 1 possessed remarkable anti-TMV activity, with an inhibition rate of 28.2%.
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Antivirais , Química , Farmacologia , Medicamentos de Ervas Chinesas , Química , Farmacologia , Flavonas , Química , Farmacologia , Garcinia , Química , Espectroscopia de Ressonância Magnética , Folhas de Planta , Química , Vírus do Mosaico do TabacoRESUMO
Objective To investigate the differences of miRNA-21 and miRNA-146a expression between colorectal neoplasms tissues and serum of the patients with colorectal neoplasm,and the clinical significance was analyzed.Methods The endoscopic biopsy tissues and serum samples of 100 colorectal cancer (CRC),80 colorectal adenoma (CRA)patients and 65 healthy controls were collected.The expressions of miRNA-21 and miRNA-146a were detected by quantitative real time polymerase chain reaction.The relationship between the expression and clinicopathological features were analyzed.And then,the diagnostic value of expression difference of serum miRNA in colorectal neoplasm were evaluated. The Mann-WhitneyU test and Kruskal-Wallis test were performed for comparisons between groups,and the correlation of miRNA expression between tissues and serum was analyzed by Spearman test.Results The expressions of miRNA-21 in the tissues of CRC and CRA were 8.573 ±0.898 and 7.746 ±1 .183, respectively,which were significantly higher than that of healthy controls 6.160 ±0.835 (U =120.129 and 33.230,both P 0.05 ).The expression of miRNA-146a in the tissues and serum of CRC patients were both lower than those of CRA patients (U =73.809 and 21 .123, both P <0.01).The degree of decreased expression of miRNA-146a in CRC patients was correlated with TNM staging and tumor differentiation degree,however there was no correlation between the expression in CRA and clinical features.According to receiver operating characteristic (ROC)curve analysis,the AUC of miRNA-21 ,miRNA-146a and a combination of them in CRC and health individuals was 0.889, 0.791 and 0.863,respectively;in CRA and health individuals was 0.784,0.692 and 0.761 ,respectively;in CRC and CRA was 0.705 ,0.820 and 0.713,respectively.Conclusion The different expressions of miRNA-21 and miRNA-146a had potential values in early detection of colorectal cancer.
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Objective: To study the chemical constituents in the stem barks of Lindera caudata. Methods: The chemical constituents from the stem barks of L. caudata were isolated by column chromatographic methods of silica gel, MCI-Gel resin, Sephadex LH-20, and high performance liquid chromatography. The structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. The cytotoxicity of this compound for NB4, A549, SHSY5Y, PC3, and MCF7 cells line was also observed by using the MTT method. Results: A 8-O-4′-neolignan, caudatalignan A (1) was isolated from this plants. Conclusion: Compound 1 is a new compound and displays the cytotoxicity against NB4 and SHSY5Y cells with IC50 values of 4.2 and 5.0 μmol/L, respectively.
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The aim of this study was to investigate the effects of hypoxia conditioned medium (HCM) of cerebral cortex cells on the differentiation of neural stem cells (NSCs) and to clarify the signal transduction mechanism. The cerebral cortex cells from newborn SD rats were primarily cultured for 5 d, and then the cells were cultured in environments of 4% O2, 1% O2 and normal oxygen concentration, respectively, for 6 h. The culture mediums were collected and centrifuged as the HCM and normoxia conditioned medium (NCM). The neurospheres of NSCs were obtained from the rat cerebral cortex by suspending culture. Immunohistochemical staining was used after adherence culture for 48 h to identify neurons and astrocytes in the progeny of NSCs. LY294002, a PI3-K inhibitor, and SP600125, a JNK inhibitor, were added into the HCM to culture NSCs for 48 h. The results showed that NSCs in the cerebral cortex could differentiate into β-Tubulin III immunoreactive neurons and GFAP immunoreactive astrocytes in three conditioned mediums, and the neurons proportion in progeny of NSCs was higher than astrocytes in all three groups. The proportion of neurons in 4% HCM was higher than that in NCM (P < 0.01). But the proportion of neurons in 1% HCM was less than that in NCM (P < 0.01). Both LY294002 and SP600125 inhibited NSCs to differentiate into high proportion neurons induced by 4% HCM (P < 0.01), but the inhibitory effect of LY294002 was stronger than that of SP600125 (P < 0.01). In conclusion, 4% HCM can induce NSCs to differentiate into more neurons mainly through the PI3-K pathway.