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Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.
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Azacitidina , Leucemia Mieloide Aguda , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Azacitidina/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SulfonamidasRESUMEN
OBJECTIVE: To explore the potential targets and synergistic mechanisms of Kushen Decoction for the treatment of cryptosporidiosis using network pharmacology and molecular docking methods. METHODS: The main active ingredients of Kushen Decoction were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TC-MSP) and the Universal Protein Resource (UniProt) database, and the potential targets were predicted. In addition, the active ingredients of Kushen Decoction that were not included in the TCMSP database were retrieved in CNKI, WanFang Data, CBM, PubMed and Web of Science databases, and the target genes of all supplemented active ingredients were predicted using the online TargetNet database. Network construction and analysis were performed using the Cytoscape software, and cryptosporidiosis-related targets were retrieved in the Comparative Toxicogenomics Database and GeneCards database. The protein-protein interaction (PPI) network was created using the STRING database, and the DAVID database was used for GO enrichment and KEGG pathway analyses. The tissue distribution of key targets was investigated using the BioGPS database, and the AutoDockTools software was employed to verify the molecular docking results. RESULTS: A total of 38 active ingredients of Kushen Decoction were screened, and the core ingredients included quercetin, (+)-14α-hydroxymatrine and apigenin. A total of 831 targets of Kushen Decoction and 512 cryptosporidiosis-related targets were predicted, and PPI network analysis revealed 69 key targets, including AKT1, TNF and IL-6. There were 303 biological processes, 46 molecular functions and 29 cellular components involved in the treatment of cryptosporidiosis with Kushen Decoction, and 13 KEGG pathways played a therapeutic role in the synergistic mechanisms of multiple targets, such as Toll-like receptor (TLR), nuclear factor kappa B(NF)-κB, nucleotide binding oligomerization domain like receptor (NLR) signal pathways. The core targets were mainly distributed in the hematologic and immune systems. Molecular docking analysis showed that the binding energy between active ingredients and key targets were all less than 0 kJ/mol, indicating the strong binding of ligands to receptors. CONCLUSIONS: The active ingredients of Kushen Decoction, such as quercetin, (+)-14α-hydroxymatrine and apigenin, may act on targets like AKT1, TNF, IL-6 to modulate TLR, NLR and NF-κB signaling pathways to play a synergistic role in the treatment of cryptosporidiosis in the hematologic and immune system.
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Criptosporidiosis , Medicamentos Herbarios Chinos , Criptosporidiosis/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Medicina Tradicional China , Simulación del Acoplamiento MolecularRESUMEN
The objective of this study was to assess whether vitamin D (VD) treatment alters the overall all-cause and cardiovascular mortalities in a chronic kidney disease (CKD) population. We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials without language restriction, until the publication date of 22 February 2016. All related literatures that compared VD treatment with non-VD treatment and reported the mortality of patients with CKD (including those undergoing dialysis) were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated by using the random- and fixed-effects models. Randomised controlled trials (RCTs) that used the intention-to-treat principle and observational studies (OSs) were analysed separately. For this study, 38 studies involving 223 429 patients (17 RCTs, n=1819 and 21 OSs, n=221610) were included. In the OSs, VD treatment was significantly associated with reductions in both all-cause and cardiovascular mortalities; however, such significant association was not found in the RCTs. The existing RCTs do not provide sufficient or precise evidence that VD supplementation affects the mortality of patients with CKD, although subsets of patients that could potentially benefit from VD treatment can be identified by using the existing data from the RCTs. Nevertheless, large-size RCTs are needed in the future to assess any potential differences in survival prospectively.
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Suplementos Dietéticos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/mortalidad , Vitamina D/administración & dosificación , Humanos , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Vitamina D/sangreRESUMEN
OBJECTIVE: The aim of the study is to investigate the correlation between tumor necrosis factor (TNF-α), E-selectin and coronary artery flow following myocardial ischemia-reperfusion model (IR) in Yorkshire pigs. MATERIALS AND METHODS: Establishment of IR model in pigs. Following the injury model, Experiment group was administrated intravenously Shenfu injection solution (SFI, 1 mL/kg). The control group received the same amount of saline. After 30 min of blood reflux, thrombolysis in myocardial infarction frame count (TFC) was recorded following surgery. TNF-α, E-selectin expression was determined by ELISA in the venous sheath, coronary sinus, artery sinus, and proximal segment of the coronary artery. RESULTS: After the blood reflowing, TFC in both groups were upregulated, and TFC increased more than the control group. The difference is statistically significant (p<0.05) at the time of 30 min. TNF-α, E-selectin expression increased after IR. After reperfusion, TNF-α, E-selectin levels further increased and the myocardial injury was aggravated. SFI inhibited inflammation in the experimental group. TNF-α, E-selectin levels at coronary sinus, artery sinus, and distal segment of coronary artery after surgery was positively correlated with TIMI in the experimental group (p<0.05). TNF-α, E-selectin levels significantly increased after reperfusion (p<0.05). CONCLUSIONS: The result demonstrated that TNF-α, E-selectin levels were positively correlated with coronary artery reflow only in the experimental group but not in the control group.
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Vasos Coronarios/fisiopatología , Selectina E/metabolismo , Isquemia Miocárdica/fisiopatología , Flujo Sanguíneo Regional , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Medicamentos Herbarios Chinos/farmacología , Isquemia Miocárdica/sangre , PorcinosRESUMEN
OBJECTIVE: To analyze the correlation between local interleukin-6 (IL-6) levels in different parts of blood vessel and the record of Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) after myocardial ischemia-reperfusion (IR) model. MATERIALS AND METHODS: Establishment of IR model in Yorkshire pigs, the pigs were divided into two groups (n=6). Experiment group pigs were administrated with Shenfu injection (SF) intravenously (1 mL/kg), control group was given saline injection. The blood reflowed after 30 min. TIMI was recorded to evaluate the coronary blood flow and myocardial perfusion. IL-6 levels in venous sheath, coronary sinus, artery sinus, and proximal coronary artery were determined by ELISA. RESULTS: The records of TIMI in experimental group were higher than that in control group. The difference was statistically significant (p < 0.05). The level of IL-6 increased obviously compared with control group after reperfusion (p < 0.05). Shenfu injection reduced the level of IL-6. IL-6 level at the coronary sinus was positively correlated with TIMI in experimental group (p = 0.03, R2 = 0.97) but not in control group. CONCLUSIONS: IL-6 levels were significantly increased after reperfusion, which aggravated myocardial injury. IL-6 may be associated with coronary reflow, but further study is needed.
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Circulación Coronaria , Interleucina-6/sangre , Infarto del Miocardio/fisiopatología , Animales , Medicamentos Herbarios Chinos/farmacología , Corazón/fisiopatología , PorcinosRESUMEN
OBJECTIVE: High vasopermeability and excessive inflammation following severe burns may result in tissue edema, organ dysfunction and the loss of circulatory plasma volume, which can influence the doctor to do the prognosis to the patients. The study aims to examine whether Xuebijing injection (XBJ), an extracts of a traditional Chinese medicine used to treat sepsis in clinic, can reduces fluid requirements by inhibiting vasopermeability and tissue edema in a canine model after burn injury. METHODS: Twenty-four beagle dogs were subjected to 50% TBSA burns, and then were randomly allocated to the following three groups: lactated Ringer's resuscitation (LR) group (n = 8), immediate LR containing Xuebijing injection (LR/XBJ) group (n = 8), and operation control group (n = 8). Hemodynamic variables and net fluid accumulation were measured. Blood samples were collected for measurement of hematocrit and circulatory plasma volume (PV). At 24 h after burn injury, heart, lung, small intestine and kidney were harvested for evaluation of the activities of myeloperoxidase (MPO) and neutrophil elastase (NE), vasopermeability, tissue water content and the amount of neutrophil infiltration. RESULTS: XBJ treatment significantly reduced net fluid accumulation, and pulmonary vascular permeability index (PVPI), extravascular lung water index (ELWI), and water content of heart, small intestine, kidney and lung compared with LR group. Furthermore, XBJ infusion significantly reduced tissue activities of MPO and NE compared with LR group. The amount of neutrophil infiltration in LR/XBJ group was lower than that in LR group. CONCLUSIONS: These results indicate that XBJ injection can reduce fluid requirements by inhibition of neutrophil protease-induced high vasopermeability and tissue edema.
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Quemaduras/tratamiento farmacológico , Permeabilidad Capilar/efectos de los fármacos , Modelos Animales de Enfermedad , Perros/lesiones , Medicamentos Herbarios Chinos/farmacología , Fluidoterapia , Soluciones Isotónicas/farmacología , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Inyecciones Intravenosas , Soluciones Isotónicas/administración & dosificación , Soluciones Isotónicas/uso terapéutico , Distribución Aleatoria , Resucitación , Lactato de RingerRESUMEN
BACKGROUND/OBJECTIVES: Branched-chain amino acids (BCAAs) and purine nucleotide cycle (PNC) are both associated with energy metabolism. The purpose of this study was to explore the influences of BCAA supplementation on the PNC activity of male athletes in response to a bout of endurance running exercise. SUBJECTS/METHODS: Twelve male athletes (20.3±1.4 years) participated in the study. Each of the athletes received 12 g of a BCAA supplement (leucine 54%, isoleucine 19% and valine 27%) per day during the study. They performed two identical 60-min running exercises (65-70% maximum heart rate reserved) before and after receiving the BCAA supplements for 15 days. In addition to body composition measurement, plasma and urinary samples were also collected. Plasma samples were examined for the concentrations of glucose, lactate, BCAAs, alanine, glutamine, aspartate, hypoxanthine and uric acid. Urinary samples were examined for the concentrations of urea nitrogen, hydroxyproline, 3-methylhistidine and creatinine. RESULTS: Body composition and the concentrations of urinary metabolites were not affected by BCAA supplementation, whereas clearance of plasma lactate after recovery from exercise was enhanced by BCAA supplementation (P<0.05). Plasma aspartate concentration was increased (P<0.05), whereas plasma glutamine, hypoxanthine and uric acid concentrations were decreased (P<0.05) by BCAA supplementation. CONCLUSIONS: The findings suggest that BCAA supplements not only provided additional substrate to meet the energy demands of the athletes during endurance exercise but also reduced their PNC activity, and subsequently decreased uric acid production and reduced the incidence of gout in a person engaging in endurance exercise.
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Aminoácidos de Cadena Ramificada/administración & dosificación , Nucleótidos de Purina/metabolismo , Carrera/fisiología , Fenómenos Fisiológicos en la Nutrición Deportiva , Adolescente , Aminoácidos de Cadena Ramificada/sangre , Antropometría , Atletas , Glucemia/metabolismo , Composición Corporal , Suplementos Dietéticos , Glutamina/sangre , Humanos , Hipoxantina/sangre , Isoleucina/administración & dosificación , Isoleucina/sangre , Leucina/administración & dosificación , Leucina/sangre , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Resistencia Física , Proyectos Piloto , Ácido Úrico/sangre , Urinálisis , Valina/administración & dosificación , Valina/sangre , Adulto JovenRESUMEN
The garden chrysanthemum (Chrysanthemum x morifolium) variety 'Aoyunhuoju' (2n = 6x = 54) was crossed as female with Ajania pacifica (2n = 10x = 90) to produce an intergeneric F1 hybrid, which was used both as a source ofF2 progeny and as a parent for a first back-cross with 'Aoyunhuoju'. The morphology of all of the F1 hybrids and hybrid derivatives was intermediate with respect to the two parents, although the BC1 progenies resembled 'Aoyunhuoju' more closely than any of the F1 and F2 progenies did. In the F1 hybrid, the density of silvery hairs on the lower leaf surface and along the margin of the leaf was lower than in A. pacifica, while that in the BC1 generation, this trait was less prominent than in the F1. The somatic chromosome number of the F1, F2 (with an exception of F2-6 of a mainly 63) and BC1 generations was 2n = 8x = 72, 2n = 8x = 72 and 2n = 7x = 63 respectively, as expected. The hybrids and their derivatives retained a variable degree of fertility. There was a low frequency of meiotic chromosome pairing failure in all three hybrid generations, with most of the chromosomes involved as bivalents. Some BC1 individuals show potential for commercialization thanks both to their flower shape and the inheritance of the silvery leaf trait from A. pacifica.
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Cromosomas de las Plantas/genética , Chrysanthemum/genética , Flores/genética , Hibridación Genética/genética , Cruzamientos Genéticos , Cariotipo , Meiosis , Hojas de la Planta/genética , Polen/citología , Polen/genética , Poliploidía , Recombinación GenéticaRESUMEN
Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.
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Adyuvantes Inmunológicos/farmacología , Enfermedad Celíaca/inmunología , Glútenes/inmunología , Interleucina-15/inmunología , Tretinoina/farmacología , Administración Oral , Adolescente , Adulto , Animales , Enfermedad Celíaca/inducido químicamente , Enfermedad Celíaca/etiología , Células Cultivadas , Niño , Preescolar , Técnicas de Cocultivo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/enzimología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Dieta , Factores de Transcripción Forkhead/metabolismo , Gliadina/administración & dosificación , Gliadina/inmunología , Glútenes/administración & dosificación , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/inmunología , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Inflamación/inmunología , Interleucina-12/biosíntesis , Interleucina-12/inmunología , Interleucina-12/metabolismo , Interleucina-15/genética , Interleucina-23/inmunología , Interleucina-23/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Receptores de Interleucina-12/deficiencia , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Tretinoina/inmunología , Adulto JovenRESUMEN
In this report, we investigated the role of oxidative stress in Physalis angulata-induced apoptosis of human oral cancer cells. P. angulata-induced apoptosis was characterized by nuclear morphological changes, membrane blebbing and activation of caspase-9. Exposure of HSC-3 cells to P. angulata caused production of reactive oxygen species and up-regulation of oxidative stress markers heme oxygenase-1 (HO-1), superoxide dismutase (SOD), heat shock protein 70 (HSP70) and caspase-4. Down-regulation of HO-1, SOD and HSP70 proteins expression by attenuation of oxidative stress, pretreatment with glutathione or N-acetylcysteine, significantly decreased P. angulata-triggered cell death. The present study also demonstrated that the mitochondria and the endoplasmic reticulum are the targets of P. angulata in HSC-3 cells. Our results revealed that: (1) reactive oxygen species may play a dominant role in this process, (2) P. angulata induces oxidative stress in HSC-3 cells, (3) P. angulata-initiated apoptosis is caused through oxidative stress-dependent induction of heme oxygenase-1, Cu/Zn SOD and HSP70 proteins expression and (4) antioxidants inhibited P. angulata-induced cell death through inhibition of the proteins expression of HO-1, Cu/Zn SOD and HSP70.
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Neoplasias de la Boca/patología , Estrés Oxidativo , Physalis/química , Extractos Vegetales/farmacología , División Celular , Línea Celular Tumoral , Fase G2 , Humanos , Microscopía Fluorescente , Neoplasias de la Boca/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Electroacupuncture (EA) has long been used as conservative treatment for low back pain (LBP). Its effect on relief of back pain has been demonstrated in many clinical studies. However, whether it has any effect on the biological properties of an intervertebral disc, which is one of the major causes of LBP, is still unclear. The aim of this study was, therefore, to investigate the effects of EA with different simulation frequencies on an intervertebral disc with simulated degeneration using an in-vivo rat-tail model. In this study, 33 rats were used. Disc degeneration was simulated in the rat caudal 8-9 disc via continuous static compressive loading of 11 N for 2 weeks. EA with a frequency of 2 or 100 Hz was then applied to the degenerated disc for 3 weeks with 3 sessions/week and 20 min/session. The intervertebral disc height was measured before and after compression as well as after EA intervention for 3 weeks. The static compression was found to result in a reduction in the disc height of about 22 per cent. There was no evidence that this change could be reversed after resting or the EA intervention. However, EA at 100 Hz was found to induce a further decrease in disc height, which was not shown for the rats after resting or EA at 2 Hz. The results of this study showed that effects of EA on disc degeneration are frequency dependent and adverse effects could result if EA at a certain frequency was used.
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Modelos Animales de Enfermedad , Electroacupuntura/métodos , Desplazamiento del Disco Intervertebral/fisiopatología , Desplazamiento del Disco Intervertebral/terapia , Inestabilidad de la Articulación/fisiopatología , Animales , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico , Inestabilidad de la Articulación/diagnóstico , Masculino , Ratas , Ratas Sprague-Dawley , Cola (estructura animal)/fisiopatología , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the neuroprotective effects and underlying mechanism of QingKaiLing (QKL) as an adjuvant treatment for bacterial meningitis. METHOD: E. coli bacterial meningitis rabbits were treated with antibiotics (ampicillin) alone or in combination with QKL. The number of leukocytes and the concentration of protein in the cerebrospinal fluid (CSF) of rabbits were determined at 0, 16, and 26 hours after treatment. Brain water, sodium, potassium, and calcium contents were determined at the 26-hour time point. The level of matrix metalloproteinase-9 in the brain was also determined by Western blot. RESULT: The average number of leukocytes and the concentration of protein in CSF of the QKL adjuvant treatment group were reduced compared with the ampicillin alone group. Brain water, sodium, and calcium contents were reduced in the QKL adjuvant treatment group. The level of MMP-9 in brain tissue was also reduced in the QKL adjuvant treatment group. CONCLUSION: QKL adjuvant treatment alleviates the aggravated inflammatory reaction and partially protects brain tissue from antibiotic-induced injury. The mechanism of this neuroprotective effect of QKL may be due to decreased levels of Ca2+ and MMP-9 in the brain.
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Antibacterianos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Encefalitis/tratamiento farmacológico , Meningitis por Escherichia coli/tratamiento farmacológico , Enfermedad Aguda , Animales , Quimioterapia Adyuvante , Combinación de Medicamentos , Fármacos Neuroprotectores/administración & dosificación , Conejos , Resultado del TratamientoRESUMEN
Intraventricular infusion of rats with beta-amyloid for 14 days resulted in memory deficit in the water maze as well as decreases in choline acetyltransferase activities and somatostatin levels in the cerebral cortex and hippocampus. These changes were not altered by daily intraperitoneal injection of 20 mg/Kg melatonin. Orally administered Ginkgo biloba extract, however, partially reversed the memory deficit and the decrease in choline actyltransferase activities in the hippocampus. The latter treatment failed to reverse the decrease in somatostatin levels. The results indicate that orally administered Ginkgo biloba extract can protect the brain against beta-amyloid from changes leading to memory deficit through its effect on the cholinergic system.
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Péptidos beta-Amiloides/toxicidad , Antioxidantes/farmacología , Encéfalo/enzimología , Colina O-Acetiltransferasa/metabolismo , Ginkgo biloba , Melatonina/farmacología , Trastornos de la Memoria/prevención & control , Fragmentos de Péptidos/toxicidad , Administración Oral , Péptidos beta-Amiloides/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inyecciones Intraperitoneales , Inyecciones Intraventriculares , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Melatonina/administración & dosificación , Trastornos de la Memoria/inducido químicamente , Fragmentos de Péptidos/administración & dosificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Somatostatina/metabolismoRESUMEN
Increasing evidence has demonstrated that nitric oxide (NO) is involved in central cardiovascular regulation. In this study, we directly measured extracellular NO levels, in real-time, in the nucleus tractus solitarius (NTS) of anesthetized cats using Nafion/Porphyrine/o-Phenylenediamine-coated NO sensors. We found that local application of L-arginine (L-Arg) induced NO overflow in NTS and hypotension. These responses were potentiated in the vagotomized animals. Pretreatment with NO synthase (NOS)/guanylate cyclase inhibitor methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or NO scavenger hemoglobin attenuated L-Arg-induced hypotension, suggesting that exogenous supplement of NO suppressed cardiac functions through the NOS/cyclic guanosine monophosphate mechanism. The role of endogenous NO was examined after local application of N(G)-nitro-L-arginine methyl ester (L-NAME). We found that L-NAME suppressed endogenous NO levels in NTS and elicited hypertension and tachycardia. Taken together, our data suggest that NO is tonically released in the NTS to inhibit blood pressure.
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Presión Sanguínea/efectos de los fármacos , Óxido Nítrico/fisiología , Núcleo Solitario/efectos de los fármacos , Animales , Arginina/farmacología , Arginina/toxicidad , Técnicas Biosensibles , Bradicardia/inducido químicamente , Gatos , Sistemas de Computación , Electroquímica , Inhibidores Enzimáticos/farmacología , Espacio Extracelular/química , Femenino , Guanosina Monofosfato/fisiología , Guanilato Ciclasa/antagonistas & inhibidores , Hemoglobinas/farmacología , Hipertensión/inducido químicamente , Hipotensión/inducido químicamente , Masculino , Azul de Metileno/farmacología , NG-Nitroarginina Metil Éster/farmacología , NG-Nitroarginina Metil Éster/toxicidad , Óxido Nítrico Sintasa/antagonistas & inhibidores , Oxadiazoles/farmacología , Presorreceptores/efectos de los fármacos , Quinoxalinas/farmacología , Reflejo/efectos de los fármacos , Sensibilidad y Especificidad , Núcleo Solitario/fisiología , Taquicardia/inducido químicamente , VagotomíaRESUMEN
OBJECTIVE: To evaluate the effects of coordination exercise on postural stability in older individuals by Chinese shadow boxing, Tai Chi Chuan (TCC). DESIGN: Cross-sectional study. SETTING: Research project in a hospital-based biomechanical laboratory. PARTICIPANTS: The TCC group (n = 25) had been practicing TCC regularly for 2 to 35 years. The control group (n = 14) included healthy and active older subjects. INTERVENTION: Static postural stability test: progressively harder sequential tests with 6 combinations of vision (eyes open, eyes closed, sway-referenced) and support (fixed, sway-referenced); and dynamic balance test: 3 tests of weight shifting (left to right, forward-backward, multidirectional) at 3 speeds. MAIN OUTCOME MEASURES: Static and dynamic balance of Sensory Organization Testing (SOT) of the Smart Balance Master System. RESULTS: In static postural control, the results showed no differences between the TCC or control group in the more simple conditions, but in the more complicated SOT (eyes closed with sway surface, sway vision with sway surface), the TCC group had significantly better results than the control group. The TCC group also had significantly better results in the rhythmic forward-backward weight-shifting test. Duration of practice did not seem to affect the stability of elder people. CONCLUSION: The elderly people who regularly practiced TCC showed better postural stability in the more challenged conditions than those who do not (eg, the condition with simultaneous disturbance of vision and proprioception). TCC as a coordination exercise may reduce the risk of a fall through maintaining the ability of posture control.
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Envejecimiento/fisiología , Boxeo/fisiología , Ejercicio Físico/fisiología , Postura/fisiología , Adolescente , Adulto , Anciano , Niño , Preescolar , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study examined the cognitive effects of chronic in vivo exposure to beta-amyloid(1-40) via the intracerebroventricular route on two distinct paradigms. The first test evaluated a form of early attentional control referred to as sensorimotor gating in which an antecedent weak prepulse stimulus modulates the reactivity to a subsequent startle-eliciting stimulus. The second test utilized the spontaneous preference for a novel object over that of a familiar one in rats as a measure of object recognition memory. We found that beta-amyloid exposure leads to a severe deficit in the object memory test but spares sensorimotor gating. Moreover, unlike the water maze deficit induced by beta-amyloid (Nag et al., in preparation), the deficit on object recognition was resistant to amelioration by systemic physostigmine treatment at a dose of 0.06 mg/kg per day intraperitoneally. The present results add to previous reports that beta-amyloid exposure can lead to deficits on hippocampal lesion sensitive tasks, suggesting that dysfunction of the rhinal cortices in addition to that of the septohippocampal system is implicated in beta-amyloid-induced behavioral impairments. It therefore lends support to the hypothesis that beta-amyloid exposure can lead to severe impairment across multiple memory systems.
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Péptidos beta-Amiloides/farmacología , Inhibidores de la Colinesterasa/farmacología , Actividad Motora/efectos de los fármacos , Paratión/farmacología , Fragmentos de Péptidos/farmacología , Reconocimiento en Psicología/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Estimulación Acústica/métodos , Animales , Ventrículos Cerebrales/efectos de los fármacos , Ventrículos Cerebrales/fisiología , Corteza Entorrinal/efectos de los fármacos , Corteza Entorrinal/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Masculino , Actividad Motora/fisiología , Ratas , Ratas Sprague-Dawley , Reconocimiento en Psicología/fisiología , Reflejo de Sobresalto/fisiologíaRESUMEN
OBJECTIVE: Telomerase activation is a common event in malignant transformation, and is associated with tumorigenesis. This has been clarified in nasopharyngeal carcinoma. YIQIJIEDU powder (Chinese traditional medicine) is used to treated the patients with nasopharyngeal carcinoma (NPC) after radio-therapy and patients with precancerous lesion of NPC. We investigated whether YIQIJIEDU powder inhibits the telomerase activity in nasopharyngeal carcinogenesis. METHODS: Nasopharyngeal carcinomas in rats were induced by N, N' Dinitrosopiperazine (DNP), and some of them were treated with YIQIJIEDU powder. Telomerase and telomerase RNA in the rats' nasopharyngeal tissue were assayed by using PCR-ELISSA and Nested-PCR, and were pathologically diagnosed. RESULTS: YIQIJIEDU powder could inhibit telomerase activity and nasopharyngeal carcinogenesis in the nasopharyngeal tissue of the rats treated, but no telomerase RNA. CONCLUSION: The findings suggest that the anticancer effect of YIQIJIEDU powder links with their inhibitory effects on telomerase.
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Medicamentos Herbarios Chinos/farmacología , Neoplasias Nasofaríngeas/enzimología , Telomerasa/biosíntesis , Animales , Femenino , Masculino , Lesiones Precancerosas/enzimología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Telomerasa/genéticaRESUMEN
A herbal literature survey was carried out on data concerning historical pharmacognostical changes of "dentifrice" in China and how diseases of the teeth and gums had been treated there in ancient times. It had been considered to be a matter of utmost importance that to prevent teeth from decaying, only the brushing of teeth with a toothbrush was necessary. Over time, various tooth agents have been found to treat oral diseases the teeth and gums. Glycyrrhizae Radix, Ginseng Radix, Scutellariae Radix, Menthae Herbal, and salt were widely used materials. Investigations from all approaches are being carried out to develop remedies for oral diseases, including Kampo medicine and the pharmacological effects of numerous crude drugs. When tracing the pharmacognostical changes of dentifrice in ancient China, we felt wonder at and admiration for the abundance of clinical experiences described in the old herbal and medical literature we researched.
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Plantas Medicinales , Cepillado Dental/historia , Pastas de Dientes/historia , China , Historia Antigua , Historia Pre Moderna 1451-1600 , Historia Medieval , Historia Moderna 1601-RESUMEN
OBJECTIVE: To compare the effects of selenium-enriched garlic (Se-garlic), garlic, Na2SeO3, and garlic + Na2SeO3 on growth of human gastric carcinoma cells. METHODS: In vivo and in vitro assays were carried out in the cultured human gastric carcinoma cell line MGC803 transplanted in the nude mice by cell count, flow cytometry, Western blot and neoplasm volume measurement. RESULTS: The inhibition effect of garlic was similar to that of Se-garlic, but Na2SeO3 was weaker than Se-garlic. Combination of garlic and Na2SeO3 was stronger than Se-garlic. In flow cytometry assay, the proportion of G1 phase was increased after 24 hour treatment of Se-garlic, garlic and Na2SeO3 in the non-synchronized cells. However, the proportion of S phase was increased in the synchronized cells. The proportion of G2 + M phase was increased both in non-synchronized and synchronized cells on treatment with the combination of garlic and Na2SeO3. The amount of Cdk2-CyclinE complex and Cdk4-CyclinD1 complex was decreased in all treated synchronized cells in immunoprecipitation and immunoblot assays. The growth of MGC803 tumor in male Balb/c nude mice was inhibited by administration of 1.67% of Se-garlic (Se 2 micrograms/g) in diet with an inhibition rate of 29.92% in tumor weight. Treatment of either 0.83% of Se-garlic or 1.67% of garlic or 4.38 micrograms/g of Na2SeO3 (Se 2 micrograms/g) could not appreciably inhibit the growth of tumor. Wrapping of a number of monocytes around the tumor was induced in 62.50% of tumors in 0.83% of the Se-garlic group. CONCLUSION: In vitro, Se-garlic is able to inhibit the growth of MGC803 cell through action of garlic. In vivo, Segarlic is able to inhibit growth of MGC803 tumor in nude mice by being better than garlic and selenite.
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Quinasas CDC2-CDC28 , Ajo , Neoplasias Experimentales/fisiopatología , Proteínas Proto-Oncogénicas , Neoplasias Gástricas/fisiopatología , Animales , División Celular/efectos de los fármacos , Ciclina D1/metabolismo , Ciclina E/metabolismo , Quinasa 2 Dependiente de la Ciclina , Quinasa 4 Dependiente de la Ciclina , Quinasas Ciclina-Dependientes/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Selenio , Compuestos de Selenio/farmacología , Óxidos de Selenio , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Células Tumorales CultivadasRESUMEN
Epidemiological and animal studies have indicated that consumption of green tea and high vitamin E intake are associated with a reduced risk of developing certain forms of cancer. However, the inhibitory mechanism of green tea catechins and vitamin E in angiogenesis, an important process in tumor growth, has not been well established. In the present study, alpha-tocopherol and several major catechins of green tea (catechin, epicatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate) were tested for their ability to inhibit tube formation in vitro using a model in which human microvascular endothelial cells were exposed to a constant rate of a physiologically low level of H2O2. In this model, the production of interleukin (IL)-8 by human microvascular endothelial cells at a low level of H2O2 was required for angiogenesis, as assessed by tube formation in three-dimensional gel in culture. Vitamin E (d-alpha-tocopherol, 40 microM) in the culture media significantly reduced IL-8 production and angiogenesis. Among the green tea catechins, epigallocatechin (0.5-1 microM) was the most effective in reducing IL-8 production and inhibiting angiogenesis. These results suggest that consumption of green tea catechins or supplemental intake of vitamin E may have preventive effects on tumor development, mediated, at least in part, through inhibition of angiogenesis via suppression of IL-8 production.