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Objective:To analyze the medication characteristics of ancient prescriptions for pediatric epilepsy (PE) through data mining; To summarize the compatibility law; To provide a reference for the treatment selection of Chinese materia medica and the development of patent drugs related to PE in clinic.Methods:Those with definite composition, dosage and efficacy for the treatment of PE was screened from the data of TCM prescription designed by Institute of Traditional Chinese Medicine Information, China Academy of Traditional Chinese Medicine. Excel 2013 was used to analyze the frequency of Chinese materia medica and its flavor and meridian tropism in the included prescriptions. The arules package in R 3.6.3 was used for association analysis based on Apriori algorithm. The sankey package and ggraph package of R 3.6.3 were used to draw the network diagram of the property, taste, meridian tropism and association rules of high-frequency Chinese medicine, so as to realize data visualization.Results:A total of 360 ancient prescriptions for the treatment of PE were included, and the dosage form was mainly pills. Most of the prescriptions were composed of 1 to 10 kinds of Chinese materia medica, with a total of 192 (53.33%, 192/360) prescriptions. 152 kinds of Chinese materia medica were included. The most commonly used types of Chinese materia medica were Glycyrrhizae Radix et Rhizoma, Moschus, Saposhnikoviae Radix, Gastrodiae Rhizoma, and Aconiti Lateralis Radix Praeparata. The properties of high-frequency Chinese materia medica (frequency≥30) were characterized by warm and mild, and the tastes were mainly pungent, bitter and sweet, and the meridians were mainly spleen and liver meridians. Through Apriori association analysis, the commonly used combination drugs were Bovis Calculus-Moschus, Ginseng Radix et Rhizoma-Poria and Saposheikovize Radix-Glycyrrhizae Radix et Rhizoma. Similarly, the commonly used triple drugs included Gastrodiae Rhizoma-Aconiti Lateralis Radix Praeparata-Bombyx Batryticatus, Poria-Glycyrrhizae Radix et Rhizoma-Ginseng Radix et Rhizoma, and Moschus-Bovis Calculus-Realgar.Conclusions:The ancient prescriptions for the treatment of PE is mainly composed of wind-calming, resuscitation and tonifying drug. The core prescription ideas of the ancient prescriptions are as follows: dispelling phlegm and dispelling wind, warming the meridian and dispelling yang, resuscitating and relieving spasms, clearing heat and reducing depression, and tonifying qi and blood.
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Objective:To compare the efficacy of single-agent versus multi-agent adjuvant chemotherapy after radical gastrectomy for elderly patients with stage Ⅲ gastric cancer.Methods:The propensity score matching and retrospective cohort study were conducted. The clinicopatholo-gical data of 456 elderly patients with stage Ⅲ gastric cancer who underwent D 2 radical resection in the Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine from January 2016 to December 2020 were collected. There were 343 males and 113 females, aged 71(range, 65?89)years. Of the 456 patients, 274 cases undergoing single-agent adjuvant chemotherapy after surgery were divided into single-agent chemotherapy group, 182 cases undergoing double-agent or triple-agent adjuvant chemotherapy after surgery were divided into multi-agent chemotherapy group. Observa-tion indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) adverse events during chemotherapy; (3) follow-up. Propensity score matching was done by the 1∶1 ratio, with the caliper value of 0.05. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parameter rank sum test. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 456 patients, 306 cases were successfully matched, including 153 cases in the single-agent chemotherapy group and 153 cases in the multi-agent chemotherapy group. The elimination of age, age-adjusted Charlson comorbidity index, pathological TNM staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Adverse events during chemotherapy. In terms of hematological adverse events, 6 cases in the single-agent chemotherapy group and 16 cases in the multi-agent chemotherapy group had neutropenia, showing a significant difference in the neutropenia ( χ2=4.90, P<0.05). In terms of non-hematological adverse events, cases with anorexia and nausea were 77 and 50 for the single-agent chemotherapy group, versus 96 and 69 for the multi-agent chemotherapy group, showing significant differences between the two groups ( χ2=4.80, 4.96, P<0.05). (3)Follow-up. All the 306 patients were followed up for 48(range, 8?61)months. The 5-year overall survival rates of the single-agent chemotherapy group and the multi-agent chemotherapy group were 36.08% and 38.31%, respectively, showing no significant difference between the two groups ( hazard ratio=0.93, 95% confidence interval as 0.70?1.20, P>0.05). Results of further analysis showed that the 5-year overall survival rates were 32.41% and 39.40% for 97 patients of the single-agent chemotherapy group and 97 patients with double-agent regimen of the multi-agent chemotherapy group, respectively, showing no significant difference between them ( hazard ratio=1.20, 95% confidence interval as 0.82?1.70, P>0.05). The 5-year overall survival rates were 43.15% and 37.11% for 56 patients of the single-agent chemotherapy group and 56 patients with triple-agent regimen of the multi-agent chemotherapy group, respectively, showing no significant difference between them ( hazard ratio=0.81, 95% confidence interval as 0.65?1.00, P>0.05). Conclusions:For adjuvant chemotherapy in elderly patients with stage Ⅲ gastric cancer, there is no significant survival advantage of double-agent or triple-agent chemotherapy over single-agent oral chemotherapy. However, there is a higher incidence of neutropenia, anorexia, ausea.
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OBJECTIVE@#To define the nature and origin of a chromosomal aberration in a child with unexplained growth and development retardation, and to analyze its genotype-phenotype correlation.@*METHODS@#A child who had presented at the Affiliated Children's Hospital of Zhengzhou University on July 9, 2019 was selected as the study subject. Chromosomal karyotypes of the child and her parents were determined with routine G-banding analysis. Their genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array).@*RESULTS@#Karyotyping analysis combined with SNP array suggested that the chromosomal karyotype of the child was 46,XX,dup(7)(q34q36.3), whilst no karyotypic abnormality was found in either of her parents. SNP array has identified a de novo 20.6 Mb duplication at 7q34q36.3 [arr[hg19] 7q34q36.3(138335828_158923941)×3] in the child.@*CONCLUSION@#The partial trisomy 7q carried by the child was rated as a de novo pathogenic variant. SNP array can clarify the nature and origin of chromosomal aberrations. Analysis of the correlation between genotype and phenotype can facilitate the clinical diagnosis and genetic counseling.
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Feminino , Humanos , Trissomia/genética , Fenótipo , Genótipo , Cariotipagem , Bandeamento CromossômicoRESUMO
Objective:To evaluate the efficacy and safety of the combination of apatinib and S-1 for treatment of patients with advanced gastric cancer, in order to provide clinical therapy reference for advanced gastric cancer.Methods:Clinical trials were retrieved from China National Knowledge Infrastructure (CNKI) , Chinese Science and Technology Journal Database (CSTJ) , Wanfang Medical Network, VIP Journal Database (VIP) , China Biomedical Literature Database (CBMdisc) , Cochrane Library, PubMed, etc., searched from Jan. 2010 to Oct. 2019. The experimental group were given apatinib combined with S-1, and the control group received S-1 monotherapy. Two sets of RCT in patients with advanced gastric cancer were collected. Researchers first screened literature, data extraction and to assess the risk of bias, then made Meta analysis with RevMan5.3 software, the test level was α=0.05.Results:A total of 12 Meta analysis of randomized RCT were selected from the group, including 561 cases of patients. The results showed that objective response rate (ORR) and disease control rate (DCR) of the experimental group was higher than those of the control group [ (RD=0.16, 95% CI: 0.08-0.23, P<0.0001; RD=0.21,95% CI: 0.14-0.29, P<0.00001) ]; There was no significant difference in nausea and vomiting, hand-foot syndrome, fatigue, diarrhea, thrombocytopenia, neutropenia, leukopenia, neuro-toxicity and mucositis between the two groups. The rate of hypertension, proteinuria, hemoglobin of the experimental group decrease was higher than that of the control group [ (OR=6.21, 95% CI: 1.92-20.13, P=0.002; OR = 10.57,95% CI: 5.06-22.04, P<0.00001; OR=2.84, 95% CI:1.25-6.48, P=0.01) ]; and there was a significant heterogeneity in hypertension among them ( P=0.008, I 2=63) . Conclusion:Compared with S-1 alone, the treatment effect of S-1 combined with targeted drug apatinib can significantly improve ORR and DCR of patients with advanced gastric cancer.
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@#Objective To evaluate whether long frozen elephant trunk (FET) increases the risk of spinal cord injury in patients with acute type A aortic dissection. Methods From 2018 to 2019, 172 patients with acute type A aortic dissection were treated in Guangdong Provincial People’s Hospital. They were divided into two groups according to the length of FET: patients treated with stents of 100 mm in length were enrolled into a short FET group, and those with stents of 150 mm in length into a long FET group. There were 124 patients in the short FET group, including 108 (87.1%) males and 16 (12.9%) females with a mean age of 51.8±7.9 years. There were 48 patients in the long FET group, including 44 (91.7%) males and 4 (8.3%) females with a mean age of 50.6±9.7 years. The clinical data and prognosis of the patients were analyzed. Results The mean distal stent graft was at the level of T 8.5±0.7 in the long FET group, and at the level of T 6.8±0.6 in the short FET group (P=0.001). Sixteen patients died after operation in the two groups, including 13 (10.5%) in the short FET group and 3 (6.2%) in the long FET group (P=0.561). There were 7 patients of spinal cord injury in the two groups, including 6 (4.8%) in the short FET group and 1 (2.2%) in the long FET group (P=0.675). There was no statistical difference in other complications between the two groups. The follow-up time was 16.7 (1-30) months. During the follow-up, 2 patients died in the long FET group and 5 died in the short FET group. No new spinal cord injury or distal reintervention occurred during the follow-up. Conclusion Long FET does not increase the incidence of spinal cord injury in patients with acute type A aortic dissection.
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Objective:To investigate the application value of laparoscopic intra-gastric surgery (LIGS) in the treatment of gastrointestinal stromal tumors (GIST) around the cardia.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients who underwent LIGS for GIST around the cardia in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2019 to December 2021 were collected. There were 3 males and 2 females, aged 52(range, 35?69)years. All patients underwent LIGS. Observation indicators: (1) intraoperative and postoperative conditions; (2) follow-up. Follow-up was conducted using tele-phone interview or outpatient examination. Patients were followed up once every 3 months to detect long-term complications and tumor recurrence up to April 1st, 2022. Measurement data with skewed distribution were represented as M(range) and count data were described as absolute numbers. Results:(1) Intraoperative and postoperative conditions. All 5 patients underwent LIGS successfully, without conversion to laparotomy or changes in surgical methods. Intraoperative tumor exploration showed that the tumor was located on the lesser curvature of the cardia in 3 patients and on the posterior wall of the gastric fundus in 2 patients. The distance between the tumor and the dentate line of the cardia was 1.5(range, 1.0?3.0)cm. Of the 5 patients, 3 cases with tumor patholo-gically evaluable margins as 0.3, 0.8, and 1.5 cm and 2 cases without tumor pathologically evaluable margins but the tumor had an intact capsule. The operation time, volume of intraoperative blood loss, time to postoperative first anal exsufflation, time to postoperative initial fluid diet intake, time to extubation and duration of postoperative hospital stay were 75(range, 65?112)minutes, 25(range, 15?70)mL, 2(range, 1?3)days, 3(range, 2?4)days, 4(range, 3?5)days and 6(range, 5?8)days in the 5 patients. There was no short-term postoperative complication such as bleeding, anastomotic leakage, and gastroparesis in the 5 patients and results of postoperative histopathological examina-tion showed GIST in all 5 patients, with tumor diameter as 3.0(range, 1.8?5.5)cm. There were 2 patients with tumor diameter ≤2.0 cm and 3 patients with tumor diameter ≥3.0 cm. The 5 patients were classified as very low risk in 2 cases, low risk in 2 cases, and intermediate risk in 1 case. (2) Follow-up. All 5 patients were followed up after operation, with the follow-up time of 9(range, 3?15)months. During the follow-up, there was no long-term complication such as dysphagia and gastroesophageal reflux, and no recurrence or metastasis of tumor occurred in patients by computed tomography examinations.Conclusion:LIGS can be used for the treatment of GIST around the cardia.
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OBJECTIVE@#To explore the genetic basis for a child with clinically suspected 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD).@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the proband and her parents. Whole exome sequencing was used to screen pathogenic variant in the proband. Suspected variant was verified by Sanger sequencing. Impact of the variant on the structure and function of protein product was analyzed by using bioinformatic software.@*RESULTS@#Sanger sequencing showed that the proband has carried homozygous missense c.1342G>A (p.Gly448Ala) variant of the MCCC2 gene, for which her mother was a heterozygous carrier. The same variant was not detected in her father. The variant was predicted to be pathogenic by PolyPhen-2 and Mutation Taster software, and the site was highly conserved among various species. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.1342G>A (p.Gly448Ala) variant of MCCC2 gene was predicted to be likely pathogenic(PM2+PP2-PP5).@*CONCLUSION@#The homozygous missense variant of the MCCC2 gene c.1342G>A (p.Gly448Ala) probably underlay the molecular pathogenesis of the proband. Genetic testing has confirmed the clinical diagnosis.
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Criança , Feminino , Humanos , Masculino , Carbono-Carbono Ligases/genética , Mutação de Sentido Incorreto/genética , Linhagem , Distúrbios Congênitos do Ciclo da Ureia/genéticaRESUMO
Objective:To determine the role of type Ⅱ alveolar epithelial stem cells (AEC Ⅱ) in radiation-induced pulmonary injury and investigate the potential mechanism by observing the dynamic changes in the expression levels of anti-prosurfactant protein C (proSP-C) proSP-C (AEC Ⅱ biomarker), homeobox only protein X (HOPX, type I alveolar epithelial cell biomarker) or vimentin (a mesenchymal marker) and transforming growth factor β 1(TGF-β 1), a profibrotic cytokine. Methods:Eight-week old C57BL/6j female mice were exposed to X-ray thoracic irradiation. Mouse lungs were collected at 8 different time points of 24 h, 1 week, 1 to 6 months after irradiation. The histopathological changes of the lungs at different time points were observed with H& E staining to determine the time of formation of pulmonary fibrosis. In addition, the co-expression of proSP-C with HOPX or vimentin in AEC Ⅱ was confirmed by immunofluorescence staining to track AEC Ⅱ phenotypes at different injury phases following thoracic irradiation. The expression levels of those proteins and TGF-β 1 were quantitatively detected by Western blot. Results:After thoracic exposure to a single dose of 20 Gy X-ray for 3 months, the fibrotic lesions in the lungs could be noted. The co-expression of proSP-C with vimentin or HOPX could be observed in AEC Ⅱ. Western blot demonstrated that the expression levels of TGF-β 1 and those proteins were also changed along with the lung injury. Conclusion:AEC Ⅱ can be differentiated into mesenchymal-like cells after X-ray irradiation due to the up-regulated expression of TGF-β 1, which is a potential cause of radiation-induced pulmonary fibrosis.
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OBJECTIVE@#To assess the value of detecting multiple rearrangements of MLL gene in children with acute mononuclear leukemia (AML).@*METHODS@#Eighty six children with AML were analyzed by fluorescence in situ hybridization (FISH), chromosomal karyotyping and multiplex reverse transcription-PCR (RT-PCR).@*RESULTS@#Cross signals were detected by FISH in 26 cases, and 30.2% were detected with MLL gene rearrangements. R-band karyotyping analysis revealed 14 translocations with breakages involving 11q23 and 5 other aberrations, which yielded an overall detection rate of 22.1%. Multiple RT-PCR has detected 12 fusion genes produced by the MLL translocation, which yielded a detection rate of 14.0%. A significant difference was found in the detection rate of the three methods (P< 0.05).@*CONCLUSION@#Combined use of FISH, chromosomal karyotyping and multiplex RT-PCR can improve the detection of MLL gene rearrangements and provide important clues for clinical diagnosis, treatment and prognosis of AML.
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Criança , Humanos , Cromossomos Humanos Par 11 , Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Genética , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mieloide Aguda , Genética , Proteína de Leucina Linfoide-Mieloide , Genética , Translocação GenéticaRESUMO
OBJECTIVE@#To assess the value of detecting the rearrangement of mixed lineage leukemia (MLL) gene in children with acute mononuclear leukemia (AML).@*METHODS@#Dual-color fluorescence in situ hybridization (FISH) probe was used to detect MLL gene rearrangement in 68 children with AML by interphase FISH. The results were compared with that of conventional G banding chromosomal analysis.@*RESULTS@#Among the 68 children, 28 were detected by FISH with positive hybridization signals, with a detection rate for MLL gene rearrangement being 41.2%. Twelve (17.6%) reciprocal translocations and interruption of 11q23 were detected by G banding analysis. The difference in the detection rates between the two methods was statistically significant (P< 0.05).@*CONCLUSION@#The sensitivity of FISH assay for MLL gene rearrangement was significantly higher than that of G banding chromosomal karyotyping. Combined use of both methods for children with AML can improve the detection rate of MLL gene rearrangements and provide crucial clues for clinical diagnosis, treatment and prognosis.
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Criança , Humanos , Cromossomos Humanos Par 11 , Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Genética , Hibridização in Situ Fluorescente , Leucemia Monocítica Aguda , Genética , Proteína de Leucina Linfoide-Mieloide , Genética , Translocação GenéticaRESUMO
Objective@#To assess the value of detecting multiple rearrangements of MLL gene in children with acute mononuclear leukemia (AML).@*Methods@#Eighty six children with AML were analyzed by fluorescence in situ hybridization (FISH), chromosomal karyotyping and multiplex reverse transcription-PCR (RT-PCR).@*Results@#Cross signals were detected by FISH in 26 cases, and 30.2% were detected with MLL gene rearrangements. R-band karyotyping analysis revealed 14 translocations with breakages involving 11q23 and 5 other aberrations, which yielded an overall detection rate of 22.1%. Multiple RT-PCR has detected 12 fusion genes produced by the MLL translocation, which yielded a detection rate of 14.0%. A significant difference was found in the detection rate of the three methods (P<0.05).@*Conclusion@#Combined use of FISH, chromosomal karyotyping and multiplex RT-PCR can improve the detection of MLL gene rearrangements and provide important clues for clinical diagnosis, treatment and prognosis of AML.
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A series of genistein-polyamine conjugates (4a-4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50 value of 2.75 μmol/L, which was better than that of rivastigmine (5.60 μmol/L). Lineweaver-Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a-4h did not affect HepG-2 cell viability at the concentration of 10 μmol/L.
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OBJECTIVE:To observe therapeutic efficacy and liver toxicity of chemotherapy combined with bevacizumab in the treatment of colorectal cancer liver metastases (CLMs). METHODS:126 CLMs patients were selected and randomly divided into chemotherapy group(54 cases)and combination group(72 cases). Chemotherapy group received FOLFOXIRI regimen:irinotecan 165 mg/m2+oxaliplatin 85 mg/m2+calcium folinate 200 mg/m2+fluorouracil 2 g. Combination group was additionally given bevaci-zumab 5 mg/kg one day before chemotherapy on the basis of FOLFOXIRI regimen. A treatment course of 2 groups lasted for 2 weeks,and both received 12 courses of treatment. The pathological response,survival rate and toxic reactions caused by chemother-apy were compared between 2 groups. RESULTS:Pathological complete response proportion,tumor remission rating(TRG),the proportion of patients with tumor necrosis rate ≥50% in combination group were significantly higher than chemotherapy group, with statistical significance (P0.05). CONCLU-SIONS:Chemotherapy combined with bevacizumab can improve pathological response and the incidence of CLMs necrosis and doesn't increase liver toxicity.
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Arsenic trioxide (ATO) has been identified as an effective treatment for acute promyelocytic leukemia (APL) but is much less effective against solid tumors such as hepatocellular carcinoma (HCC). In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yl)tryptophan methyl ester (ETME). Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP) in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.
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There are some existing problems in controlling the quality of oxygen. In order to improve quality, efficiency and safety in the use of oxygen, we presented some factors which may give rise to variations in concentration of oxygen and proposed some suggestions based on the investigation and analysis of such problems.
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Equipamentos e Provisões , OxigênioRESUMO
A series of quinoline-polyamine conjugates (8a-8n) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). Some of these compounds had potent ChEs inhibitory activity with IC50 values at micromolar range. Compound 8n exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 8.78 micromol x L(-1), and compound 8i showed the most potent inhibition on butyrylcholinesterase (BChE) with IC50 value of 1.60 micromol x L(-1) which was slightly better than rivastigmine. The structure-activity relationship revealed that the chain length of polyamine and linker played important roles for inhibitory activity. Molecular modeling studies showed that 8i targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of cholinesterases.
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The gamma-cyclodextrin-folate (gamma-CD/FA) inclusion-coated CdSe/ZnS quantum dots (QDs) with folate-receptor (FR) targeted were synthesized by simple and convenient sonochemical method. The products were studied using Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), utraviolet-visible spectrometry (UV-vis), fluorescence spectrum and transmission electron micrographs (TEM). The results showed that the gamma-CD/FA-coated CdSe/ZnS QDs not only have good monodispersity and smaller size, but also have good optical performance, such as higher quantum yield (QY) and a long fluorescence lifetime. The cytotoxicity experiments showed that the gamma-CD/FA-coated CdSe/ZnS QDs have lower cytotoxicity and could more effectively enter cancer cells with FR over-expression. The QDs with 4-5 nm in diameter were relatively easy to enter the cell and to be removed through kidneys, so it is more suitable for biomedical applications for bioprobes and bioimaging.
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A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range. Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic and molecular modeling studies showed that these hybrids targeted both the catalytic active site and the peripheral anionic site of AChE.
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This study is to examine the effects of NNIspm-mediated cellular senescence of HepG2 cells and elucidate its potential molecular mechanism. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution, intracellular fluorescence intensity and accumulation of intracellular reactive oxygen species (ROS) were detected by high content screening (HCS). Protein expression was detected by Western blotting. Polyamines content was analyzed by high performance liquid chromatography (HPLC). The results demonstrated that NNIspm significantly induced HepG2 cells senescence. This effect was due to the decrease of intracellular polyamines, the arrest at G0/G1 phase and an increase of ROS level. The molecular senescence marker p21 increased significantly after NNIspm treatment. In contrast, the protein expressions of Cyclin E and CDK2 were obvious down-regulation. The results indicated that cellular senescence induced by NNIspm was one of its antitumor mechanisms.
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The objective of this study is to examine the effects of ANISpm, a novel polyamine naphthalimide conjugate, with acetylsalicylic acid against hepatocellular carcinoma in vivo and in vitro and elucidate its potential molecular mechanism. The proliferation inhibition was detected by MTT assay. Cell apoptosis, intracellular fluorescence intensity and mitochondrial membrane potential (MMP) were detected by high content screening (HCS) analysis. Polyamines content was analyzed by reverse-phase high performance liquid chromatography Protein expression levels were quantified by Western blotting assay. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis in HepG2 cells and H22 hepatoma cells, which was mediated by enhanced ANISpm uptake via up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) and depression of intracellular polyamine. Furthermore, this synergistic apoptosis was involved in mitochondria and death-receptor signal pathway. All these findings demonstrated that the combination treatment with acetylsalicylic acid and ANISpm resulted in synergistic antitumor effects on hepatoma cells. Thus, combination therapy with these agents may be useful as a potential template for the development of better chemotherapeutic strategy against hepatoma.