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OBJECTIVE: To investigate the mechanism of the antidepressant-like effects of Chaihu Guizhi decoction (CGD). OBJECTIVE: Chaihu Guizhi decoction at the daily dose of 17 g/kg and solvent vehicle were administered by gavage in 12 and 14 male C57BL/6J mice for 7 consecutive days, respectively. Forced swimming test (FST), elevated plus maze (EPM) test, open field test (OFT) and novelty-suppressed feeding test (NSF) were performed to assess the depression- and anxiety-like behaviors and motor ability of the mice. We further used chronic social defeat stress (CSDS) and social interaction test to evaluate the antidepressant-like effects of CGD in comparison with the solvent vehicle. Western blotting and RT-qPCR were performed to detect the expressions of sirt1, p53, acetylated p53, and the neuron plasticity-related genes including synapsin I (Syn1), Rab4B, SNAP25 and tubulin beta4b in the hippocampus of the mice. OBJECTIVE: In FST, the immobility time of CGDtreated mice was decreased significantly (P < 0.05); no significant differences were found in the performances in EPM, NSF and OFT tests between the two groups. In social interaction test, the mouse models of CSDS treated with CGD showed significantly increased time in the interaction zone (P < 0.05). Compared with those in the vehicle group, the CGD-treated mouse models exhibited significantly increased protein level of SIRT1 and decreased p53 acetylation (P < 0.05) with up-regulated synapsin I mRNA expression in the hippocampus (P < 0.05); no significant difference were found in Rab (P=0.813), SNAP (P=0.820), or Tubb mRNA expressions (P=0.864) between the two groups. OBJECTIVE: CGD produces antidepressant-like effects in mice possibly through the sirt1-p53 signaling pathway and synaptic plasticity.
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Sirtuina 1 , Proteína p53 Supresora de Tumor , Animales , Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Hipocampo , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Sirtuina 1/genética , Estrés Psicológico/tratamiento farmacológicoRESUMEN
PURPOSE: The use and contribution of prenatal multivitamins (PMV) as iodine source for pregnant women in China, especially in mildly iodine-deficient region, have not been well studied. This study aimed to explore the association between PMV intake during pregnancy and thyroid function in mothers and newborns. METHODS: We performed a study involving women with a history of taking PMV during pregnancy between January 2013 and October 2015, in Shanghai, a mildly iodine-deficient region. Maternal thyroid function in early and late pregnancy, and neonatal TSH on postnatal d 3 were obtained from medical records. We compared the outcomes in pregnant women who took exclusively iodine-containing PMV (I + PMV) with those who took exclusively non-contained PMV (I- PMV). Propensity score matching (PSM) was used to identify women with similar baseline characteristics. RESULTS: After PSM, 1280 women in I + PMV and 2560 in I- PMV had similar propensity scores and were included in the analyses. Introduction of I + PMV to women was associated with slightly higher maternal thyroid hormone production (higher maternal FT4, p = 0.01, non-significantly lower TSH, p = 0.79) and lower neonatal TSH levels (p < 0.0001). The frequency of adverse pregnancy outcomes or thyroid dysfunctions did not differ between groups in late pregnancy. Mothers received I + PMV (0.2 SD) had a stronger association of maternal TSH with neonatal TSH than those who received I- PMV (0.1 SD). These effects were only shown in TPOAb-negative mothers, not in TPOAb-positive mothers. CONCLUSION: TPOAb-positive women display an impaired iodine transport in thyroid and placenta, and this may explain the lack of changes in maternal and neonatal thyroid parameters with I + PMV supplementation in these women. This phenomenon might suggest that these women require different iodine doses or treatment approach in comparison with TPOAb-negative women.
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Suplementos Dietéticos , Yodo/administración & dosificación , Yodo/deficiencia , Intercambio Materno-Fetal/efectos de los fármacos , Enfermedades de la Tiroides/tratamiento farmacológico , Glándula Tiroides/efectos de los fármacos , Vitaminas/administración & dosificación , Adulto , Femenino , Humanos , Recién Nacido , Edad Materna , Embarazo , Resultado del Embarazo , Enfermedades de la Tiroides/metabolismo , Enfermedades de la Tiroides/patología , Glándula Tiroides/metabolismo , Hormonas Tiroideas/metabolismoRESUMEN
OBJECTIVE: To observe the effects of Fei-Liu-Ping ointment and chemotherapy on mice with lung cancer, and to explore the inherent mechanism of action from the point of acidic microenvironment and apoptosis. METHODS: First of all, the Lewis lung cancer transplanted mouse model was established. Therefore, they were treated by Fei-Liu-Ping ointment, cyclophosphamide, Fei-Liu-Ping ointment + cyclophosphamide and the saline as control. All the groups' tumor size, tumor growth rate and food consumption were recorded. The mice were sacrificed and the tumors were took out after 15 days' interventions. Then lactate relative concentrations were detected with lactate kits and the protein expressions of glucose transporter 4 (GLUT4), hexokinase 1 (HK1), glucose-regulated protein 78 (GRP78), carbonic anhydrase-IX (CA-IX) were detected through immunohistochemical staining. Flow cytometry was adopted to detect the percentage of apoptotic tumor cells and regulatory T cells (Treg), and the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2, Bax, Caspase-3, interleukin-2 (IL-2) were tested through western blot. RESULTS: The strongest inhibition effect and the lowest tumor growth rate was found in Fei-Liu-Ping ointment + cyclophosphamide group. There were significant differences between Fei-Liu-Ping ointment + cyclophosphamide group and saline group(P<0.05). And the highest food consumption was found in Fei-Liu-Ping ointment + cyclophosphamide group while there were no significant differences between Fei-Liu-Ping ointment + cyclophosphamide group and saline group (P>0.05). Further molecular biological detections found that the lowest lactate level and regulatory T cells ratio were found in Fei-Liu-Ping ointment + cyclophosphamide group and these expressions of GLUT4, HK1, GRP78, CA-IX were suppressed. There were significant differences between Fei-Liu-Ping ointment+cyclophosphamide group and saline group (P<0.05). In addition, the Fei-Liu-Ping ointment + cyclophosphamide group's cell apoptosis increased significantly compared with saline group and there were significant differences on expressions of HIF-1α, Bcl-2, Bax, Caspase-3, IL-2 for this group compared with saline group. CONCLUSION: Chemotherapy and Fei-Liu-Ping ointment had the synergistic effect on inhibiting tumor growth and improving the general conditions of tumor-bearing mice. The effect was partly owed to the improvement on tissue hypoxia, the inhibition of HIF-1α expression and the regulations on its downstream proteins, such as GLUT4, HK1, GRP78, and CA-IX. And then all these alterations led to the modulation tumor acidic microenvironment, the induced tumor cells apoptosis and suppression of T cells to regulatory T cells differentiation.
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Neoplasias Pulmonares , Animales , Apoptosis , Proliferación Celular , Ciclofosfamida , Medicamentos Herbarios Chinos , Chaperón BiP del Retículo Endoplásmico , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones , Microambiente TumoralRESUMEN
The effects of dietary supplementation with lysine-yielding Bacillus subtilis on gut morphology, cecal microflora, and expression of intestinal cytokine mRNA of Linwu ducks (a Chinese local domesticated duck) were investigated after a 63-d feeding trial. Two hundred forty 1-d-old female ducklings were randomly assigned to 1 of 4 dietary treatments, and there were 60 birds per treatment replicated 6 times with 10 birds each. The experimental diets consisted of a basal diet containing no antibiotic or growth promoters, the basal diet supplemented with 150 mg Aureomycin per kg feed, and 2 others supplemented with 5.0 × 108 and 5.0 × 1010 cfu B. subtilis/kg feed, respectively. Birds fed the diets supplemented with B. subtilis had increased (P < 0.001) villi height in the jejunum and ileum and reduced (P < 0.001) crypt depth in the jejunum compared with birds fed the control diet. Greatest (P < 0.01) villus height:crypt depth ratio was obtained with the jejunum and ileum of birds fed the diet supplemented with 5.0 × 1010 cfu B. subtilis/kg feed. Dietary supplementation with B. subtilis resulted in increased (P < 0.05) cecal counts of Megasphaera elsdenii. Greater cecal Lactobacillus counts were obtained in ducks fed the diets supplemented with Aureomycin and B. subtilis. Ducks fed the diets supplemented with B. subtilis showed suppressed (P < 0.001) expression of interleukin (IL)-1ß, IL-2, and IL-10 in their jejunum. When compared with the control, the expression of interferon (IFN)-γ in the jejunum of ducks fed the diet supplemented with 5.0 × 108 cfu B. subtilis/kg feed was significantly increased (P < 0.05). Dietary supplementation with B. subtilis or Aureomycin reduced (P < 0.001) ileal expression of IL-10. When compared with the control, the expression of IL-2 and IL-8 in the ileum of ducks fed the diet supplemented with 5.0 × 1010 cfu B. subtilis/kg feed showed a significant decrease (P < 0.05). In conclusion, dietary supplementation with lysine-yielding B. subtilis improved gut morphology, increased the population of beneficial gut microflora, and stimulated increased intestinal immune response of Linwu ducks.
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Alimentación Animal/análisis , Bacillus subtilis/metabolismo , Ciego/microbiología , Suplementos Dietéticos , Patos , Lisina/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Animales , Citocinas/metabolismo , Dieta/veterinaria , Femenino , Regulación de la Expresión Génica , Íleon/inmunología , Íleon/metabolismo , Intestinos/efectos de los fármacos , Lisina/farmacología , ProbióticosRESUMEN
Plant growth in semi-arid ecosystems is usually severely limited by soil nutrient availability. Alleviation of these resource stresses by fertiliser application and aboveground litter input may affect plant internal nutrient cycling in such regions. We conducted a 4-year field experiment to investigate the effects of nitrogen (N) addition (10 g N·m(-2) ·year(-1)) and plant litter manipulation on nutrient resorption of Leymus chinensis, the dominant native grass in a semi-arid grassland in northern China. Although N addition had no clear effects on N and phosphorus (P) resorption efficiencies in leaves and culms, N fertilisation generally decreased leaf N resorption proficiency by 54%, culm N resorption proficiency by 65%. Moreover, N fertilisation increased leaf P resorption proficiency by 13%, culm P resorption proficiency by 20%. Under ambient or enriched N conditions, litter addition reduced N and P resorption proficiencies in both leaves and culms. The response of P resorption proficiency to litter manipulation was more sensitive than N resorption proficiency: P resorption proficiency in leaves and culms decreased strongly with increasing litter amount under both ambient and enriched N conditions. In contrast, N resorption proficiency was not significantly affected by litter addition, except for leaf N resorption proficiency under ambient N conditions. Furthermore, although litter addition caused a general decrease of leaf and culm nutrient resorption efficiencies under both ambient and enriched N conditions, litter addition effects on nutrient resorption efficiency were much weaker than the effects of litter addition on nutrient resorption proficiency. Taken together, our results show that leaf and non-leaf organs of L. chinensis respond consistently to altered soil N availability. Our study confirms the strong effects of N addition on plant nutrient resorption processes and the potential role of aboveground litter, the most important natural fertiliser in terrestrial ecosystems, in influencing plant internal nutrient cycling.
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Nitrógeno/farmacología , Fósforo/metabolismo , Poaceae/efectos de los fármacos , Poaceae/metabolismo , China , Ecosistema , Fertilizantes , Pradera , Nitrógeno/metabolismo , Especificidad de Órganos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Tallos de la Planta/efectos de los fármacos , Tallos de la Planta/metabolismo , Suelo/químicaRESUMEN
This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.
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Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Compuestos Férricos/uso terapéutico , Hipertermia Inducida/métodos , Neoplasias Hepáticas/terapia , Magnetoterapia/métodos , Nanopartículas/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Hematínicos/uso terapéutico , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Neoplasias Hepáticas/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.
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Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Compuestos Férricos/uso terapéutico , Hipertermia Inducida/métodos , Neoplasias Hepáticas/terapia , Magnetoterapia/métodos , Nanopartículas/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Hematínicos/uso terapéutico , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Neoplasias Hepáticas/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
UNLABELLED: Previous studies have shown that isoimperatorin (IO), a furanocoumarin isolated from several medicinal plants, has antimycobacterial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294). This study demonstrated that IO has antimycobacterial activity against 2 drug-sensitive and 6 drug-resistant isolates, with minimum inhibitory concentrations (MICs) of 50-100 µg ml(-1) and 100-200 µg ml(-1), respectively. IO exhibited synergistic antimycobacterial effects with rifampin (RMP), isoniazid (INH) and ethambutol (EMB) against 6 drug-resistant strains, with fractional inhibitory concentration index (FICI) values of 0·133-0·472, 0·123-0·475 and 0·124-0·25, respectively. The IO/RMP, IO/INH and IO/EMB combination treatments had synergistic effects or no interaction in the 2 drug-sensitive strains and the standard strain ATCC 27294. The synergism of combined drugs against drug-resistant strains was better than drug-sensitive strains. No antagonism was observed in with the aforementioned combinations against all strains tested. IO exhibited relatively low cytotoxicity to Vero cells. Our results indicate that IO may serve as promising a template for future antimycobacterial drug development. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the in vitro synergistic antimycobacterial effects of isoimperatorin (IO) in combination with three first-line drugs: rifampin (RMP), isoniazid (INH) and ethambutol (EMB). The results indicated that the antimycobacterial activity of IO was modest; however, IO was a useful and effective agent against Myco. tuberculosis when it was combined with first-line antimycobacterial drugs and is worthy of further development as a lead compound for the development of novel antimycobacterial therapeutic agents.
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Antituberculosos/farmacología , Furocumarinas/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Animales , Antituberculosos/toxicidad , Chlorocebus aethiops , Sinergismo Farmacológico , Etambutol/farmacología , Furocumarinas/toxicidad , Isoniazida/farmacología , Pruebas de Sensibilidad Microbiana , Rifampin/farmacología , Células VeroRESUMEN
The establishment of high-efficiency Agrobacterium-mediated transformation techniques could improve the production of Dioscorea zingiberensis, a medicinal species with a high diosgenin content. We co-cultivated embryogenic calli induced from mature seeds with A. tumefaciens strain EHA105. A binary vector, pCAMBIA1381, which contains the gfp and hpt genes under the control of the ubiquitin promoter and the CaMV 35S promoter, respectively, was used for transformation. Pre-culture, basic medium, acetosyringone, and bacterial density were evaluated to establish the most efficient protocol. The optimal conditions consisted of MS medium without CaCl(2) for pre- and co-cultivation, three days for pre-culture, addition of 200 µM AS, and an OD(600) of 0.5. The transgenic plants grown under selection were confirmed by PCR analysis and Southern blot analysis. This protocol produced transgenic D. zingiberensis plants in seven months, with a transformation efficiency of 6%.
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Agrobacterium tumefaciens/genética , Dioscorea/genética , Ingeniería Genética/métodos , Carbenicilina/farmacología , Cinamatos/farmacología , Diosgenina/metabolismo , Resistencia a Medicamentos , Vectores Genéticos/genética , Proteínas Fluorescentes Verdes/genética , Higromicina B/análogos & derivados , Higromicina B/farmacología , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Plantas Modificadas Genéticamente/genética , Plantas Medicinales/genética , Semillas/citología , Semillas/genética , Semillas/fisiología , Transformación GenéticaRESUMEN
Many genetic disorders are due to protein misfolding and excessive premature degradation in the endoplasmic reticulum (ER). When a gene mutation does not affect the functionality of the protein, it may still promote the premature clearance of the protein by ER-associated degradation (ERAD), resulting in a loss of function. Competitive inhibitors are often effective active-site-specific chaperones when used at sub-inhibitory concentrations. Active-site-specific chaperones assist in the folding of mutant lysosomal enzymes in the ER, thereby promoting their escape from ERAD, enhancing trafficking to the lysosome and increasing the level of residual enzyme activity. In Fabry disease, degradation of various mutant forms of a-galactosidase A (alpha-gal A) has been shown to take place in the ER as a result of protein misfolding. One of the most potent inhibitors of alpha-gal A, 1-deoxygalactonojirimycin, has also been shown to be effective in enhancing residual alpha-gal A activity in cultured fibroblasts and lymphoblasts established from patients with Fabry disease caused by a variety of missense mutations. Oral administration of 1-deoxygalactonojirimycin to transgenic mice expressing a mutant form of human alpha-gal A (R301Q) yielded higher alpha-gal A activity in major tissues, compared with untreated transgenic mice.
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Sitios de Unión/efectos de los fármacos , Enfermedad de Fabry/tratamiento farmacológico , Iminoazúcares/uso terapéutico , Chaperonas Moleculares/uso terapéutico , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/uso terapéutico , Animales , Activadores de Enzimas/uso terapéutico , Enfermedad de Fabry/enzimología , Humanos , Ratones , Ratones Transgénicos , Pliegue de Proteína , alfa-Galactosidasa/genética , alfa-Galactosidasa/metabolismoRESUMEN
The Mopan persimmon (Diospyros kaki L. cv. Mopan) is the major cultivar of astringent persimmon in northern China. This study investigates the radical scavenging activity against ABTS and DPPH radical, and the content of total and individual phenolics (catechin, epicatechin, epigallocatechin, chlorogenic acid, caffeic acid, and gallic acid) with apple, grape, and tomato as controls. The radical scavenging activities against ABTS and DPPH radicals of the Mopan persimmon are 23.575 and 22.597 microm trolox eq/g f.w., respectively. These findings suggest that the Mopan persimmon's antioxidant activity is significantly (P < 0.05) stronger than that of reference materials. The Mopan persimmon showed the highest content of total phenolics among the 4 materials tested. Significant correlations (R(2)= 0.993, P < 0.05, ABTS radical; R(2)= 0.980, P < 0.05, DPPH radical) are found between the total phenolics and the radical scavenging activities. The total content of these 6 kinds of phenolics (catechin, epicatechin, epigallocatechin, chlorogenic acid, caffeic acid, and gallic acid) is significantly correlated (R(2)= 0.831, P < 0.05, ABTS radical; R(2)= 0.745, P < 0.05, DPPH radical) with the individual radical scavenging activity of the 4 materials, although the total content of the 6 phenolics accounts for no more than 20% of the total phenolics in the Mopan persimmon. Gallic acid exhibits the strongest antioxidant activity in all 6 kinds of phenolics and its content is the largest in the Mopan persimmon, presumably being responsible for its much higher antioxidant activity as compared to apple, grape, and tomato.
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Antioxidantes/farmacología , Diospyros/química , Fenoles/farmacología , Extractos Vegetales/química , Antioxidantes/análisis , Benzotiazoles , Compuestos de Bifenilo , Ácidos Cafeicos/farmacología , Catequina/farmacología , Ácido Clorogénico/farmacología , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres , Radicales Libres , Ácido Gálico/farmacología , Hidrazinas , Solanum lycopersicum/química , Malus/química , Oxidación-Reducción , Fenoles/análisis , Picratos , Ácidos Sulfónicos , Vitis/químicaRESUMEN
The extract of bark of Angylocalyx pynaertii (Leguminosae) was found to potently inhibit mammalian alpha-L-fucosidases. A thorough examination of the extract resulted in the discovery of 15 polyhydroxylated alkaloids, including the known alkaloids from seeds of this plant, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), 1-deoxymannojirimycin (DMJ) and 2,5-imino-1,2,5-trideoxy-D-mannitol (6-deoxy-DMDP). Among them, eight sugar-mimic alkaloids showed the potent inhibitory activity towards bovine epididymis alpha-L-fucosidase and their Ki values are as follows: 6-deoxy-DMDP (83 microM), 2,5-imino-1,2,5-trideoxy-L-glucitol (0.49 microM), 2,5-dideoxy-2,5-imino-D-fucitol (17 microM), 2,5-imino-1,2,5-trideoxy-D-altritol (3.7 microM), DMJ (4.7 microM), N-methyl-DMJ (30 microM), 6-O-alpha-L-rhamnopyranosyl-DMJ (Rha-DMJ, 0.06 microM), and beta-L-homofuconojirimycin (beta-HFJ, 0.0053 microM). We definitively deduced the structural requirements of inhibitors of alpha-L-fucosidase for the piperidine alkaloids (DMJ derivatives). The minimum structural feature of alpha-L-fucosidase inhibitors is the correct configuration of the three hydroxyl groups on the piperidine ring corresponding to C2, C3 and C4 of L-fucose. Furthermore, the addition of a methyl group in the correct configuration to the ring carbon atom corresponding to C5 of L-fucose generates extremely powerful inhibition of alpha-L-fucosidase. The replacement of the methyl group of beta-HFJ by a hydroxymethyl group reduced its inhibitory potential about 80-fold. This suggests that there may be a hydrophobic region in or around the active site. The existence or configuration of a substituent group on the ring carbon atom corresponding to the anomeric position of L-fucose does not appear to be important for the inhibition. Interestingly, Rha-DMJ was a 70-fold more potent inhibitor of alpha-L-fucosidase than DMJ. This implies that the lysosomal alpha-L-fucosidase may have subsites recognizing oligosaccharyl structures in natural substrates.
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Alcaloides/farmacología , Inhibidores Enzimáticos/farmacología , Fabaceae/química , Plantas Medicinales , alfa-L-Fucosidasa/antagonistas & inhibidores , 1-Desoxinojirimicina/química , 1-Desoxinojirimicina/farmacología , Alcaloides/química , Animales , Bovinos , Inhibidores Enzimáticos/química , Humanos , Tallos de la Planta/química , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To study the neurocyte apoptosis and change of cytosolic free calcium induced by hypoxia/hypoglycemia culture in SH-SY5Y human neuroblastoma cells, and the effect of Shenmai Injection (SMI) on them. METHODS: The neurocyte apoptosis rate was analysed quantitatively by flow cytometry and cytosolic calcium was determined by measuring mean fluorescent value with Fluo-3 flurometry. RESULTS: Hypoxia/hypoglycemia could induce neurocyte apoptosis and increase the cytosolic calcium in SH-SY5Y cells. SMI could inhibit the SH-SY5Y cell apoptosis and lower the concentration of cytosolic free calcium. CONCLUSION: Apoptosis is one of the death pattern of nerve cells. SMI could obviously reduce the hypoxia/hypoglycemia induced apoptosis and calcium overload, thus protect the neurocytes.
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Apoptosis/efectos de los fármacos , Calcio/metabolismo , Medicamentos Herbarios Chinos/farmacología , Fármacos Neuroprotectores/farmacología , Hipoxia de la Célula/efectos de los fármacos , Células Cultivadas , Citoplasma/metabolismo , Combinación de Medicamentos , Medicamentos Herbarios Chinos/administración & dosificación , Humanos , Neuroblastoma/patología , Neuronas/citología , Células Tumorales CultivadasRESUMEN
We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.
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Química Encefálica/genética , Proteínas Portadoras , Péptidos y Proteínas de Señalización Intracelular , Mutación , Narcolepsia/genética , Neuropéptidos/genética , Receptores de Neuropéptido/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Corteza Cerebral/química , Femenino , Pruebas Genéticas , Humanos , Hipotálamo/química , Hipotálamo/citología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Neuropéptidos/análisis , Neurotransmisores/genética , Receptores de Orexina , Orexinas , Puente/química , Procesamiento Proteico-Postraduccional , Receptores Acoplados a Proteínas G , Distribución Tisular , Población BlancaRESUMEN
A cDNA encoding putative phospholipid hydroperoxide glutathione peroxidase (PHGPX) was isolated from rice using rapid amplification of cDNA ends. This cDNA, designated ricPHGPX, includes an open reading frame encoding a protein of 169 amino acids which shares about 60% and 50% amino acid sequence identity with plant and mammalian PHGPXs, respectively. The gene is expressed at a relative high level in flag leaves and the expression can be markedly induced by oxidative stress, suggesting that the product of the gene plays a key role in defense against oxidative damage in rice.
Asunto(s)
Genes de Plantas , Glutatión Peroxidasa/genética , Oryza/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN Complementario/aislamiento & purificación , Regulación de la Expresión Génica , Datos de Secuencia Molecular , Oryza/enzimología , Estrés Oxidativo , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Alineación de Secuencia , Homología de SecuenciaRESUMEN
The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is not clear. We evaluated ASC in blood and urine of fasting male patients with idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller subgroups, we also evaluated their response to exogenous ASC [either intravenous or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test meal. The influence of ASC on calcium oxalate crystallization, the morphology of crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine incubation on urinary oxalate at these pHs, without and with addition of ASC, were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from fasting patients remained unchanged, but the slope of the regression line of urinary ASC versus urinary oxalate was steeper than in the controls; the plasma ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the ASC-supplemented meal caused an increase in the integrated plasma oxalate in the normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were increased, but urinary glycolate was unchanged. In the controls, oral ASC did not affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal growth. In control urine calcium oxalate dihydrate and calcium oxalate monohydrate develops, while in ICU urine only the former crystal type develops. In vitro oxalate neoformation from ASC did not occur. It was concluded that (1) under normal conditions an abettor role of ASC for renal stones is not recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of exogenous ASC is exhibited, and that this is most likely unrelated to an initial increase in oxalate biosynthesis, and (3) ASC appears to modulate directly calcium oxalate crystallization in ICU, although the true mode of action is still not known.
Asunto(s)
Ácido Ascórbico/orina , Oxalato de Calcio/orina , Calcio/orina , Cálculos Urinarios/sangre , Cálculos Urinarios/orina , Administración Oral , Adolescente , Adulto , Anciano , Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Calcio/sangre , Calcio/química , Oxalato de Calcio/sangre , Oxalato de Calcio/química , Cristalización , Ayuno/sangre , Ayuno/orina , Humanos , Inyecciones Intravenosas , Masculino , Recurrencia , Cálculos Urinarios/etiologíaRESUMEN
Permanent prostate implant using 125I or 103Pd sources is a common treatment choice in the management of early prostate cancer. As sources of new designs are developed and marketed for application in permanent prostate implants, it is of paramount importance that their dosimetric characteristics are carefully determined, in order to maintain a high accuracy of patient treatment. This report presents the results of experimental measurements of the dosimetric parameters performed for a newly available 125I seed source, the model MED3631-A/M source (IoGold), manufactured by North American Scientific, Inc. The measurements were performed in a large scanning water phantom, using a diode detector. The positioning of the source and the diode detector was achieved by a computer-controlled positioning mechanism in the scanning water phantom. The dose rate constant in water for the new 125I source was measured in comparison with an existing 125I source of similar design and verified using thermoluminescent dosimetry (TLD) measurement. The radial dose function values for the source were measured using the diode detector. The measurement technique and the results are compared with the dose distribution parameters for the 125I sources discussed in the AAPM TG43 report and elsewhere [Med. Phys. 26, 570-573 (1999)]. For the dose rate constant in water of the new source, it is recommended that a value of 0.950 cGy/U-hr be used based on the NIST 1985 air-kerma strength calibration standard, or 1.060 cGy/U-hr based on the 1999 NIST air-kerma strength standard. The measured radial dose function values for the MED3631-A/M source agree closely with those of the model 6702 source. It is therefore recommended that the radial dose function values for the model 6702 125I source, as recommended by the AAPM TG43 report, be adopted for the new source as well.
Asunto(s)
Braquiterapia/métodos , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Próstata/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Fenómenos Biofísicos , Biofisica , Humanos , Masculino , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador/estadística & datos numéricos , AguaRESUMEN
Permanent prostate implantation using 125I (iodine) or 103Pd (palladium) sources is a popular treatment option in the management of early prostate cancer. As sources of new designs are developed and marketed for application in permanent prostate implantations, their dosimetric characteristics must be carefully determined in order to maintain the accuracy of patient treatment. This report presents the results of experimental measurements and Monte Carlo calculations of the dosimetric parameters performed for a newly available 103Pd seed source. The measurements were performed in a large scanning water phantom using a diode detector. The positioning of the source and detector was achieved by a computer-controlled positioning mechanism in the scanning water phantom. The dose rate constant in water for the new 103Pd source was determined from measurements with the diode detector calibrated with 125I sources of known air-kerma strength. The radial dose function values for the source were measured using the diode detector. Monte Carlo photon transport calculations were then used to calculate the dosimetric parameters of dose rate constant, radial dose function, and anisotropy function using an accurate geometric model of the source. The measured dose rate constant of 0.693 cGy/U-hr compares well with the Monte Carlo calculated value of 0.677 cGy/U-hr. These results are further compared with data on existing 103Pd sources.
Asunto(s)
Braquiterapia/métodos , Paladio/uso terapéutico , Radioisótopos/uso terapéutico , Planificación de la Radioterapia Asistida por Computador/métodos , Anisotropía , Fenómenos Biofísicos , Biofisica , Braquiterapia/estadística & datos numéricos , Humanos , Masculino , Método de Montecarlo , Fotones , Neoplasias de la Próstata/radioterapia , Planificación de la Radioterapia Asistida por Computador/estadística & datos numéricos , AguaRESUMEN
The objective of this study was to determine the effect of Chinese herbs and immune inhibitors on diffuse proliferative glomerulonephritis. The tubular-interstitial infiltration of cell, TGF-beta expression and interstitial fibrosis were investigated, and the relationship between clinical data and pathological changes was analysed. The results showed the infiltration of cells was inhibited in the "Chinese herbs combined with prednisone" group, the infiltration of cells, TGF-beta expression and interstitial fibrosis were all inhibited in the cyclophosphamide and prednisone" group. But in the prednisone group, interstitial fibrosis was not inhibited. These data suggest that the combined use of Chinese herbs, immunosuppressant and prednisone can inhibit the interstitial cell infiltration and prevent the interstitial fibrosis in diffuse proliferative glomerulonephritis.