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Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.
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Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Carcinoma de Células Transicionales/patología , Reproducibilidad de los Resultados , Variaciones en el Número de Copia de ADN , Neoplasias Renales , Neoplasias Ureterales , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE@#To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury.@*METHODS@#Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side.@*RESULTS@#Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group.@*CONCLUSION@#Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.
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Masculino , Animales , Ratas , Ratas Sprague-Dawley , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Terapia por Acupuntura , Daño por Reperfusión/terapia , Isquemia Encefálica/terapia , Infarto Cerebral/terapia , Proteínas NLRRESUMEN
OBJECTIVE@#To analyze the RHD genotype of a blood donor with Del phenotype in Yunnan.@*METHODS@#Rh serological phenotype was identified. RHD gene was detected by PCR-SSP typing, and its 10 exons were sequenced. Exon 9 was amplified for sequencing and analysis. RHD zygosity was detected.@*RESULTS@#The Rh phenotype of this specimen was CcDelee. Genomic DNA exhibited a 1 003 bp deletion spanning from intron 8, across exon 9 into intron 9. The deletion breakpoints occurred between two 7-bp short tandem repeat sequences. There was no variation in the sequences of the remaining exons. The Rh hybridization box test showed that there was one RHD negative allele.@*CONCLUSION@#This specimen is Del type caused by deletion of RHD exon 9.
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Humanos , Donantes de Sangre , Sistema del Grupo Sanguíneo Rh-Hr/genética , China , Fenotipo , Exones , Genotipo , AlelosRESUMEN
The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.
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Background@#The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM. @*Methods@#This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed. @*Results@#After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients. @*Conclusion@#Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.
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Objective:To compare the regulatory effects of <italic>Polygala tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> on learning and memory, hypothalamus-pituitary-adrenal axis (HPA axis) function and neurotransmitters in rats with heart-kidney imbalance insomnia. Method:The rat model of insomnia induced by multi-factor stimulation was established. After the model being made, the administration groups were given the extracts of <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> by gavage (dose of 8 g·kg<sup>-1</sup>·d<sup>-1</sup>), while the normal group and model group were given the same volume of normal saline for 7 days. Morris water maze was used to detect the changes of learning and memory ability of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol (CORT) in serum of rats from each group. The contents of 5-hydroxytryptamine (5-HT), dopamine (DA), <italic>γ</italic>-aminobutyric acid (GABA) and glutamic acid (Glu) in the hypothalamus of rats were determined simultaneously by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Result:Compared with the normal group, the spatial learning and memory ability of rats in the model group<italic> </italic>was decreased, the times and time of staying in target quadrant were significantly reduced (<italic>P<</italic>0.05, <italic>P<</italic>0.01), the levels of CORT, CRH and ACTH in serum were significantly increased (<italic>P<</italic>0.01), the contents of GABA, DA, 5-HT in hypothalamus tissue were significantly decreased (<italic>P<</italic>0.01), and the content of Glu was significantly increased (<italic>P<</italic>0.01). Compared with the model group, the spatial learning and memory ability of rats in the <italic>P. tenuifolia</italic> group and licorice-simmered <italic>P. tenuifolia </italic>group<italic> </italic>were increased, the times and time of staying in the target quadrant were significantly increased (<italic>P<</italic>0.05, <italic>P<</italic>0.01), the levels of CORT, CRH and ACTH in serum were significantly decreased (<italic>P<</italic>0.05, <italic>P<</italic>0.01), the contents of GABA, DA and 5-HT in hypothalamus tissue were significantly increased (<italic>P<</italic>0.05, <italic>P<</italic>0.01), and the content of Glu was significantly decreased (<italic>P<</italic>0.05). The recovery degree of each index in the licorice-simmered <italic>P. tenuifolia</italic> group was better than that in the <italic>P. tenuifolia</italic> group. Conclusion:Both <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> can improve the learning and memory ability, improve the function of HPA axis, regulate the level of central neurotransmitters, and have the effect of calming the mind and improving the intelligence of rats with heart-kidney imbalance insomnia. The effect of licorice-simmered <italic>P. tenuifolia</italic> is better than that of <italic>P. tenuifolia.</italic>
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Rhizome rot disease is one of the main disease of planted Polygonatum kingianum. In this study, six strains of pathogenic fungus was isolated from P. kingianum samples with rhizome rot disease collected from six counties in Yunnan province. Its pathogenicity was confirmed by inoculation to healthy P. kingianum rhizome according to Koch's postulates. The colonies of the isolated fungi on potato dextrose agar(PDA) were orange with abundant crescentic conidia which were eseptate with a mean size of 19. 3-24. 9 μm×5. 2-5. 9 μm and a L/W ratio of 3. 4-4. 5. There was an oil ball in the center of the conidium. It's easy to see setae on PDA colony.The phylogenetic tree based on ITS, GAPDH, CHS-1, HIS3, ACT, and TUB2 sequences by maximum likelihood(ML) method indicated that the pathogenic fungus for P. kingianum rhizome rot disease was clustered into the clade of Colletotrichum spaethianum species complex, and was close to C. spaethianum. However, there were some differences in morphological and genetic characteristics between the pathogenic fungus and C. spaethianum. Therefore, the pathogenic fungus for rhizome rot disease of P. kingianum was identified as a new Colletotrichum species named C. kingianum. The disease spreads primarily due to the plantation of infected seedlings of P. kingianum. It is necessary to choose healthy seedlings and take rigorous disinfection measures for the disease prevention.
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China , Colletotrichum/genética , Filogenia , Polygonatum , RizomaRESUMEN
With the deepening of research in recent years, tumor metabolic reprogramming has gradually become the focus of research, and targeting tumor cell metabolism has also become a new means of tumor therapy. The metabolic process affects almost all the physiological processes of the organism, and lipid metabolism is an important part of the metabolic process. Studies have shown that changes in lipid uptake, storage and fatty acid synthesis and decomposition have occurred in a variety of tumors. Abnormal lipid metabolism will promote the rapid proliferation of tumors. Abnormal expression of a variety of key metabolic enzymes in the process of lipid metabolism is the key to tumor progression. The purpose of this paper is to explain the metabolic regulation of lipid metabolism and related metabolic enzymes in hematological tumors, and to provide ideas for the treatment of hematological tumors.
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In recent years, the role of ketone body metabolism in tumor growth, invasion and metastasis has attracted much attention. Succinyl-CoA transferase (SCOT) is a key enzyme in the metabolism of ketone bodies. Its function is to transfer the coenzyme A group of succinyl-CoA to acetoacetate and catalyze the formation of acetoacetyl-CoA, which is the first rate-limiting step in ketone metabolism. Then acetoacetyl-CoA further breaks into two molecules of acetyl-CoA and enters the tricarboxylic acid cycle. Studies have shown that SCOT is highly expressed in a variety of tumors, and is closely related to tumor progression and prognosis of patients, which makes SCOT a potential marker for clinical diagnosis and prognosis evaluation; in addition, inhibition of SCOT activity can hinder the metabolism of ketone bodies in tumor cells, that is, reduce the production of ATP, thereby inhibiting tumor growth, proliferation, invasion and metastasis. This review aims to explore the important role of SCOT in metabolic pathways and its relationship with tumorigenesis and development, and to provide new ideas for exploring tumor metabolism and targeting molecular drugs.
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OBJECTIVE@#To investigate the clinical significance of SCIN gene expression and promoter methylation in patients with chronic myeloid leukemia (CML).@*METHODS@#Real-time quantitative PCR was used to detect the expression level of SCIN in mononucleatr cells of bone marrow samples from 64 CML patients and 37 controls. The methylation levels of SCIN promoter in 65 patients with CML and 29 controls were detected by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR.@*RESULTS@#The expression level of SCIN in CML patients was significantly down-regulated (P<0.05), compared with the control group. The down-regulation rate of SCIN expression in CML patients at chronic phase, accelerated phase and blast crisis was 61%, 67% and 75%, respectively. Spearman correlation analysis showed that the expression level of SCIN negatively correlated with the transcript level of BCR-ABL1 (R=-0.315, P<0.05). However, there was no significant difference in clinical parameters such as sex, age, white blood cell count, hemoglobin level, platelet count, chromosome, CML staging and BCL-ABL1 transcript level between low and high SCIN expression groups of CML patients (P>0.05). No significant difference in methylation of SCIN promoter between CML patients and controls, and no correlation between SCIN expression and promoter methylation were observed (P>0.05).@*CONCLUSION@#The SCIN expression is down-regulated in CML patients, which may relate with the pathogenesis that is, BCR-ABL1 fusion gene induces CML tumorigenesis. The down-regulation of SCIN expression may relate with the progression of CML.
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Humanos , Crisis Blástica , Metilación de ADN , Regulación hacia Abajo , Proteínas de Fusión bcr-abl , Gelsolina , Genética , Leucemia Mielógena Crónica BCR-ABL Positiva , Genética , Regiones Promotoras GenéticasRESUMEN
·AIM: To compare clinical effects and cost of panretinal photocoagulation (PRP) combined with Ranibizumab or triamcinolone acetonide (TA) for diabetic macular edema (DME). ·METHODS: Forty-eight patients (48 eyes) with DME and diabetic retinopathy ( DR) receiving PRP were randomly assigned to two groups, which were respectively intravitreally injected ranibizumab (0. 5mg) and TA (4mg). Ranibizumab (0.5mg) was intravitreal injected every 4wk for 3 times. The effects of injection for DME were evaluated using best-corrected visual acuity (BCVA ), central macular thickness ( CMT ) and intraocular pressure (IOP). During the follow-up, other injections were performed to eyes which had CMT greater than 400μ m. The medical costs were calculated at 12wk and 24wk.·RESULTS: BCVA and CMT between 2 groups were not significantly different (P>0.05); BCVA and CMT among different time points were significantly different(P<0.05);the treatments and the time points had significant interaction on BCVA (P<0.05). BCVA was improved in two groups at all the time after injection(P<0.05),except 1wk after injection of TA (P=0.33). There was significant difference between the two groups at 12wk and 16wk on BCVA and that injected with ranibizumab was better (P=0.03,0.045). CMT decreased in two groups at all the time after injection (P<0.05). There was significant difference only between the two groups at 1wk (P< 0. 01). All intraocular pressures were in the normal range, except one needed ocular hypotensive agents. The medical costs (yuan) of the ranibizumab group in 12wk and 24wk were 38 736 and 42 564,which of the TA group were 5 790 and 7 053,respectively. ·CONCLUSION:Both PRP combined with ranibizumab or TA for DME can effectively control disease progression in short time. Therapeutic effect is not significant between two methods, but PRP combined with TA is more economic.
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Objective@#To investigate the association of the polymorphisms of the gene of estrogen receptor α 1 (ESR1) with the risk of hypospadias in children of Northeast China.@*METHODS@#This study included 95 hypospadias patients aged 3.2±0.6 years and 105 children aged 3.1±0.7 years as normal controls. Using PCR and gene sequencing, we determined the genotypes of the polymorphisms of ESR1 rs2077647 and rs6932902 in the two groups of subjects.@*RESULTS@#The results of PCR and gene sequencing showed statistically significant differences in the genotype and allele frequency distribution of the polymorphisms rs2077647 (χ2 = 8.552) and rs6932902 (χ2 = 16.251) (P<0.05) in the hypospadias and control groups. The hypospadias patients, in comparison with the normal controls, exhibited a markedly higher frequency of the SNP C allele in rs2077647 (OR = 1.410 [1.130-1.759], P<0.05), but a remarkably lower frequency of the SNP G allele in rs6932902 (OR = 2.263 [1.503-3.408], P<0.01).@*CONCLUSIONS@#The rs2077647 and rs6932902 polymorphisms of the ESR1 gene are associated with the risk of hypospadias, and so is its haplotype in children in Northeast China.
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Preescolar , Humanos , Masculino , Alelos , Estudios de Casos y Controles , China , Receptor alfa de Estrógeno , Genética , Genotipo , Haplotipos , Hipospadias , Genética , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
To provide guidance for quality control and variety breeding of Gastrodia elata f. glauca cultivated form in Zhaotong, nine agronomic traits of G. elata f. glauca cultivation form were measured and the traits were analyzed using multiple comparison,correlation analysis, multiple stepwise regression analysis and path analysis. The results of multiple comparison and analysis showed that the number of dot ring and the length-width ratio of tuber were no different in G. elata f. glauca cultivation form. The coefficient of variation about the single tuber fresh weigh, ring spacing and belly button diameter was about 20%. The coefficient of variation about the length of the tuber, the width of the tuber, the thickness of the tuber, the length-width ratio of tuber and the number of dot ring was near 10%. The correlation analysis results showed that the single tuber fresh weigh and the length,the width and the thickness of the tuber were extremely significant positive correlated. The results of multiple stepwise regression analysis and path analysis showed that the length, the width and the thickness of the tuber were the main factors affecting the fresh weight of single tuber,which were the best agronomic traits on high yield of G. elata f. glauca. The length of the tuber,the width of the tuber and the thickness of the tuber, which would be used as indicators of the characteristics of high yield varieties in Zhaotong. The number of dot ring and the length-width ratio of tuber, which would be selected as quality control indicators of the genuine Chinese medicinal materials in Zhaotong.
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Taking application of some isolation and purification technologies, including solvent extraction, rude solvent isolation, column chromatographies on silica gel and Sephadex LH-20 , and preparative HPLC , 4 compounds were obtained from Gynura nepalensis cultivated in a suburban area of Beijing. Their structures were identified by spectroscopic methods in conjunction with comparison of the NMR data with literature values as 7S,8R-9'-O-ethyl-dehydrodiconiferyl-9-acetate (1), 9'-O-ethyl-dehydrodiconiferyl alcohol (2), dehydrodiconiferyl-9,9'-diacetate(3), and (+)-medioresinol(4), respectively. 1 is a new 2,3-dihydrobenzofuran-8,3'-neolignane type compound, and 2-4 were isolated from G.nepalensis for the first time. The complete assignment of the 1H- and 13C-NMR spectroscopic data of the four compounds recorded in DMSO-d6 was achieved.
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In this paper, the potential distribution information and ecological suitability regionalization for Gastrodia elata in Zhaotong were studied based on the climate, terrain, soil and vegetation factors analysis by Maxent and ArcGIS. The results showed that the highly potential distribution (suitability index>0.6) mainly located in Zhaotong, Yunnan province(Zhenxiong,Yiliang and Daguan county, with an area of 2 872 km²), and Bijie, Guizhou province (Hezhang,Bijie,Weining county, 1 251 km²). The AUC of ROC curve was above 0.99, indicating that the predictive results with the Maxent model were highly precise. The main ecological factors determining the potential distribution were the altitude, average rainfall in November, average rainfall in October, vegetation types, average rainfall in March, average rainfall in April,soil types,isothermal characteristic and average rainfall in June. The environmental variables in the highly potential areas were determined as altitude around 1 450-2 200 m,annual average temperature around 18.0-20.4 ℃,annual average precipitation around 900 mm,yellow soil or yellow brown soil,and acid sandy loam or slightly acidic sandy loam.The results will provide valuable references for plantation regionalization and the siting for imitation wild planting of G. elata in Zhaotong.
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In order to provide a basis for establishing seed testing rules and seed quality standard of Bletilla striata, the seed quality of B.striata from different producing area was measured referring to the Rules for Agricultural Seed Testing(GB/T 3543-1995).The results showed that the seeds of B.striata passed through 20-mesh sieve for purity analysis.The weight of seeds was measured by 1000-seed method and the water content was measured at the higher temperature (133±2) ℃ for 3 hours.The seeds were cultured on the wet filter paper at 30 ℃ for 4-20 days in light for germination testing.The method of testing seed viability was that seeds were dipped into 1% TTC solution for 7 hours at temperature of 40 ℃.
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Ongoing study on the chemical constituents of the roots of Macleaya microcarpa led to the isolation of eight compounds of derivatives of triterpenes and organic acids in addition to some previously identified benzophenanthridines. The eight compounds were identified by spectroscopic methods as well as comparison with literature values as 1-oxo-2, 22 (30)-hopandien-29-oic acid (1), 3-oxo-12-oleanen-30-oic acid (2), 3α-hydroxy-12-oleanen-30-oic acid (3), 3β-hydroxy-12-oleanen-30-oic acid (4), ferulic acid (5), ferulic acid 4-O-β-D-glucoside (6), 3-O-feruloylquinic acid (7), and methyl 3-O-feruloylquinate (8). Of which, 1 is a new triterpenoid of hopanes and 2-8 are isolated from M microcarpa for the first time. In order to discover natural active compounds as potential agents of anti-ulcerative colitis (UC), an in vitro drug high-throughput screening model targeted x-box-binding protein 1 (xbp1) was employed to evaluate the activity of the major chemical constituents of M microcarpa. The result confirmed that two dihydrobenzophenanthridines, dihydrosanguinarine (9) and dihydrochelerythrine (10), showed a certain activity on activating the transcription of xbpl, a transcription factor (TF) associated with the occurrence, development, and potential treatment of UC, with their relative activating ratios being 1.76 and 1.77 times, respectively, as compared with control group.
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Antiulcerosos , Química , Benzofenantridinas , Química , Proteínas de Unión al ADN , Genética , Isoquinolinas , Química , Papaveraceae , Química , Raíces de Plantas , Química , Factores de Transcripción del Factor Regulador X , Factores de Transcripción , Genética , Transcripción Genética , Triterpenos , QuímicaRESUMEN
Taking application of some isolation and purification technologies, including crushing, solvent extraction, preliminary solvent isolation, column chromatographies over silica gel and Sephadex LH-20 gel and preparative HPLC, 8 compounds were obtained from the seeds of Jufeng grape sourced from market. Their structures were identified by spectroscopic methods and comparison with literature values as Catechin (1), Epicatechin (2), quercetin (3), ethylgallate (4), rel-(2S, 3R) -2-(4-hydroxy-3-methoxyphenyl) -3- (hydroxymethyl)-5-(3-hydroxypropyl)-2,3-dihydrobenzofuran-7-ol (5), rel-(2α, 3β)-7-O-methylcedrusin (6), rel-(1R,2S)-1-(4-hydroxy-3-methoxyphenyl) -2-(4-(3-hydroxypropyl) -2-methoxyphenoxy) propane-1,3-diol (7), and (+) -isolariciresinol (8), respectively. Compounds 5-8 were serial lignans isolated from the seeds of grape for the first time. Structurally, 5 and 6 belong in benzofuran-8,3'-neolignans, 7 in 8,4'-oxyneolignan, and 8 in 8,8' :2,7'-cyclolignan. According to in vitro activity evaluation conducted in cell model, compound 6 showed significant anti-oxidative ability, with the activity of RAW264. 7 cell superoxide dismutase being raised evidently in the test as compared with the positive anti-oxidative agents, compounds 1 and 2.
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Antioxidantes , Química , Espectroscopía de Resonancia Magnética , Extractos Vegetales , Química , Semillas , Química , Vitis , QuímicaRESUMEN
<p><b>BACKGROUND</b>Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL.</p><p><b>METHODS</b>We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled.</p><p><b>RESULTS</b>Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94), P = 0.02], progression-free survival (PFS) [HR = 0.61, 95% CI (0.52-0.72), P < 0.05], odds ratio (OR) [RR = 1.26, 95% CI (1.07-1.47), P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65) P =0.001].</p><p><b>CONCLUSIONS</b>After first-line chemotherapy, the two rituximab-combined treatment strategies, including maintenance and salvage therapies can bring survival benefit. But due to the few studies, the low methodological quality assessment and the low outcome evidence quality, it's not confirmed that the two strategies are better than normal chemotherapy regimens. More high-quality randomized controlled trials are still needed to provide reliable evidence. The higher rate of infections after rituximab therapy should be taken into consideration when making treatment decisions.</p>
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Humanos , Anticuerpos Monoclonales de Origen Murino , Usos Terapéuticos , Linfoma de Células B Grandes Difuso , Quimioterapia , RituximabRESUMEN
Objective: To investigate the effects of human bone morphogenetic protein 9 (BMP9) on proliferation and migration of human breast cancer MDA-MB-231 cells in simulated breast adipose microenvironment by co-culture technique, and to explore its possible mechanism. Methods: MDA-MB-231 cells were infected with recombinant adenovirus Ad-BMP9 or Ad-GFP (as the control), and then they were indirectly co-cultured with adipose progenitor 3T3-L1 cells for 3 days. The infection efficiency of recombinant adenovirus Ad-BMP9 in MDA-MB-231 cells in the co-culture system was observed under a fluorescence microscope, and the expression level of BMP9 was detected by reverse transcription (RT)-PCR and Western blotting. The effects of BMP9 overexpression on proliferation and migration of MDA-MB-231 cells were investigated by MTT method, flow cytometry, wound-healing assay and Transwell migration assay, respectively. The expression of proliferation and metastasis-related factor leptin in the cells in co-culture system was detected by Western blotting. The expressions of leptin receptor (OB-R) and the key molecules of leptin signaling pathway in MDA-MB-231 cells were detected by immunofluorescence staining and Western blotting. Results: The infection efficiency of recombinant adenovirus Ad-BMP9 in MDA-MB-231 cells in co-culture system was about 70% under a fluorescence microscope. The overexpression of BMP9 was successfully detected in MDA-MB-231 cells in co-culture system (P 2/M phase (P < 0.001). Compared with the control group, BMP9 overexpression could decrease the expession level of leptin in 3T3-L1 cells (P < 0.05), and down-regulate the expression levels of phosphorylated STAT3 (p-STAT3) (P < 0.05) and phosphorylated ERK1/2 (p-ERK1/2) (P < 0.05). Conclusion: BMP9 can inhibit the proliferation and migration of breast cancer MDA-MB-231 cells in simulated breast microenvironment by regulating the cross-talk between MDA-MB-231 cells and adipose progenitor 3T3-L1 cells. Leptin signaling pathway may be involved in this process.