RESUMO
PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use. In this study, we described a novel PI3Kδ inhibitor SAF-248, which exhibited high selectivity for PI3Kδ (IC50 = 30.6 nM) over other PI3K isoforms at both molecular and cellular levels, while sparing most of the other human protein kinases in the kinome profiling. SAF-248 exhibited superior antiproliferative activity against 27 human lymphoma and leukemia cell lines compared with the approved PI3Kδ inhibitor idelalisib. In particular, SAF-248 potently inhibited the proliferation of a panel of seven DLBCL cell lines (with GI50 values < 1 µM in 5 DLBCL cell lines). We demonstrated that SAF-248 concentration-dependently blocked PI3K signaling followed by inducing G1 phase arrest and apoptosis in DLBCL KARPAS-422, Pfeiffer and TMD8 cells. Its activity against the DLBCL cells was negatively correlated to the protein level of PI3Kα. Oral administration of SAF-248 dose-dependently inhibited the growth of xenografts derived from Pfeiffer and TMD8 cells. Activation of mTORC1, MYC and JAK/STAT signaling was observed upon prolonged treatment and co-targeting these pathways would potentiate the activity of SAF-248. Taken together, SAF-248 is a promising selective PI3Kδ inhibitor for the treatment of DLBCL and rational drug combination would further improve its efficacy.
Assuntos
Antineoplásicos/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Inibidores de Fosfoinositídeo-3 Quinase/química , Relação Estrutura-AtividadeRESUMO
Fibroblast growth factor receptor (FGFR) is a promising anticancer target. Currently, most FGFR inhibitors lack sufficient selectivity and have nonnegligible activity against kinase insert domain receptor (KDR), limiting their feasibility due to the serious side effects. Notably, compensatory activation occurs among FGFR1-4, suggesting the urgent need to develop selective pan-FGFR1-4 inhibitors. Here, we explored the antitumor activity of DW14383, a novel irreversible FGFR1-4 inhibitor. DW14383 exhibited equivalently high potent inhibition against FGFR1, 2, 3 and 4, with IC50 values of less than 0.3, 1.1, less than 0.3, and 0.5 nmol/L, respectively. It is a selective FGFR inhibitor, exhibiting more than 1100-fold selectivity for FGFR1 over recombinant KDR, making it one of the most selective FGFR inhibitors over KDR described to date. Furthermore, DW14383 significantly inhibited cellular FGFR1-4 signaling, inducing G1/S cell cycle arrest, which in turn antagonized FGFR-dependent tumor cell proliferation. In contrast, DW14383 had no obvious antiproliferative effect against cancer cell lines without FGFR aberration, further confirming its selectivity against FGFR. In representative FGFR-dependent xenograft models, DW14383 oral administration substantially suppressed tumor growth by simultaneously inhibiting tumor proliferation and angiogenesis via inhibiting FGFR signaling. In summary, DW14383 is a promising selective irreversible pan-FGFR inhibitor with pan-tumor spectrum potential in FGFR1-4 aberrant cancers, which has the potential to overcome compensatory activation among FGFR1-4.
Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Administração Oral , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/patologia , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The color of Rubus chingii was characterized by digital method, and the content of water extract, alcohol extract, total flavonoids, total polysaccharides, total polyphenols, ellagic acid, linden glycoside, kaophenol-3-O-rutin were determined. Correlation regression was used to analyze the correlation between color and composition. The results showed that L~* was positively correlated with total polyphenols, kaophenol-3-O-rutin and tilide, and moderately positively correlated with total flavones, ellagic acid and aqueous extracts. The a~* value was negatively correlated with total polyphenols, kaophenol-3-O-rutin, and linden glycosides, while was moderately correlated with total flavones, aqueous extracts, and ellagic acid. The b~* value was negatively correlated with the water extract, and moderately correlated with the content of total polyphenols, total polysaccharides, alcohol extract and kaophenol-3-O-rutin, which showed that R. chingii mature color had a significant correlation with material composition in the process of dynamic change. According to the law of dynamic change in the color and quality indexes, it is determined that the appropriate harvest time is in late April to May 1, while the fruit is not turn yellow. The agronomic traits related to fruit was(12.49±0.56) mm in diameter,(14.25±1.19)mm in height,(1.20±0.14) g in weight, the chroma L~* value was 52.87±3.14,a~* value was 2.01±1.58, b~* values was 28.31±3.88. The results lay a foundation for establishing an objective quantitative evaluation model of R. chingii color from experience.
Assuntos
Rubus , Flavonoides , Frutas , Glicosídeos , Extratos VegetaisRESUMO
Aberrant expression of CDK9/cyclin T1 has been found in diffuse large B-cell lymphoma (DLBCL), and suggests that CDK9 is a potential therapeutic target for DLBCL. Here, we firstly demonstrated that CDKI-73, a novel cyclin-dependent kinases (CDK) inhibitor, potently blocks CDK9, triggered apoptosis and dramatically repressed DLBCL cell growth owing to CDK9 inhibition. CDK9 inhibitors specifically elevated the trimethylation of H3K27, which we speculate was due to reduced expression of JMJD3/UTX. Considering the important role of the trimethylation of H3K27 in tumor progression, the synergistic effect of the combination therapy of CDK9 inhibitors with EZH2 inhibitors was investigated. EZH2 inhibitors reversed the upregulation of trimethylation of H3K27, and synergistically inhibited DLBCL and other solid tumors growth in vitro and in vivo These findings provide a rational basis for the application of CDK9 inhibitors in combination with EZH2 inhibitors in clinical trials.
Assuntos
Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Linfoma Difuso de Grandes Células B , Apoptose , Pontos de Checagem do Ciclo Celular , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Ativação Transcricional , Regulação para CimaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Deregulated Polycomb repressive complex 2 (PRC2) is intimately involved in tumorigenesis and progression, making it an invaluable target for epigenetic cancer therapy. Disrupting the EZH2-EED interaction, which is required for PRC2 enzymatic activity, is a promising strategy for cancer treatment. However, this kind of inhibitors are still limited. The in-cell protein-protein interaction screening was conducted for approximately 1300 compounds by NanoBRET technology. Co-immunoprecipitation (Co-IP), protein thermal shift assay (PTSA), and cellular thermal shift assay (CETSA) were performed to investigate the regulation of PRC2 by AZD9291. The anti-tumor effects of AZD9291 on breast cancer (BC) cells and diffuse large B-cell lymphoma (DLBCL) cells were detected. MicroRNA array assay, luciferase reporter assay, and qRT-PCR were conducted to identify the interaction and regulation among AZD9291, EZH2, and miR-34a. We discovered that, AZD9291, a potent and selective EGFR inhibitor, disrupted the interaction of EZH2-EED, leading to impairment of PRC2 activity and downregulation of EZH2 protein. In addition, AZD9291 declined EZH2 mRNA expression via upregulating the expression of a tumor suppressor, miR-34a. Our results suggest that AZD9291 can serve as a lead compound for further development of antagonist of PRC2 protein-protein interactions and EZH2 mRNA may be a direct target of miR-34a through non-canonical base pairing.
Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Complexo Repressor Polycomb 2/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , MicroRNAs/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Ligação Proteica/efeitos dos fármacos , Regulação para CimaRESUMO
OBJECTIVE: To observe the clinical efficacy of acupoint injection of Shuxuetong (SXT) in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) complicated by premature ejaculation (PE). METHODS: A total of 78 cases of CP/CPPS complicated by PE were randomly assigned to receive acupuncture injection of SXT (n = 38) and placebo acupuncture as the control (n = 40) for two 15-day courses. The therapeutic effects were evaluated based on the patients' scores on National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and Premature Ejaculation Diagnostic Tool (PEDT) before and after treatment. RESULTS: Compared with the controls, the SXT group showed a significantly higher total effectiveness rate based on either NIH-CPSI (27.5% vs 63.2%, P < 0.05) or PEDT (25% vs 47.4%, P < 0.05) and a lower deterioration rate (17.5% vs 7.9%, P < 0.05). Statistically significant differences were observed between the baselines and post-treatment scores on NIH-CPSI in the SXT group (24.82 ± 5.89 vs 15.45 ± 6.74, P < 0.05) and the controls (26.10 ± 6.59 vs 22.10 ± 8.42, P < 0.05) as well as on PEDT in the SXT group (14.87 ± 3.70 vs 10.29 ± 4.25, P < 0.05) and the controls (14.98 ± 3.09 vs 13.00 ± 4.53, P < 0.05), and both the NIH-CPSI and PEDT scores were markedly lower in the SXT than in the control group after treatment (P < 0.05). Linear regression analysis exhibited a positive correlation between the NIH-CPSI and PEDT scores before and after treatment in the SXT group (R = 0.340, P < 0.037) but not in the control group (R = 0.133, P < 0.413). CONCLUSIONS: Acupoint injection of Shuxuetong can significantly improve the symptoms of CP/CPPS and CP/CPPS-induced PE as well.
Assuntos
Pontos de Acupuntura , Dor Crônica , Medicamentos de Ervas Chinesas , Dor Pélvica , Ejaculação Precoce , Prostatite , Doença Crônica , Dor Crônica/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Masculino , Dor Pélvica/tratamento farmacológico , Dor Pélvica/etiologia , Ejaculação Precoce/complicações , Prostatite/complicações , Prostatite/tratamento farmacológicoRESUMO
Over half of patients with BRCA1-deficient cancers do not respond to treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. In this study, we report that a combination of 53BP1 and BRCA1 may serve as a biomarker of PARP inhibitor sensitivity. Based on the mRNA levels of four homologous recombination repair (HR) genes and PARP inhibitor sensitivity, we selected BRCA1-deficient MDA-MB-436 cells to conduct RNA interference. Reducing expression of 53BP1, but not the other three HR genes, was found to lower simmiparib sensitivity. Additionally, we generated 53BP1-/-/BRCA1-/- clonal variants by the transcription activator-like effector nuclease (TALEN) technique and found that depleting 53BP1 impaired PARP inhibitor sensitivity with a 36.7-fold increase in their IC50 values. Consistent with its effect on PARP inhibitor sensitivity, 53BP1 loss alleviated cell cycle arrest and apoptosis and partially restored HR function. Importantly, 53BP1 depletion dramatically reduced the ability of PARP inhibitors to suppress tumor growth in vivo. The inhibition rate of simmiparib was 74.16% for BRCA1-deficient MDA-MB-436 xenografts, but only 7.79% for 53BP1/BRCA1-deficient xenografts. Re-expressing 53BP1 in the dual-deficient cells restored PARP inhibitor sensitivity and the levels of HR regulators. Considering that at least 10% of BRCA1-deficient breast and ovarian cancers have reduced expression of 53BP1, using a combination of 53BP1 with BRCA1 as a biomarker for patient selection should reduce the number of patients undergoing futile treatment with PARP inhibitors.
Assuntos
Antineoplásicos/farmacologia , Proteína BRCA1/antagonistas & inibidores , Biomarcadores Tumorais/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Antineoplásicos/química , Proteína BRCA1/deficiência , Proteína BRCA1/metabolismo , Biomarcadores Tumorais/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Relação Estrutura-Atividade , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/deficiência , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismoRESUMO
We present MethHC (http://MethHC.mbc.nctu.edu.tw), a database comprising a systematic integration of a large collection of DNA methylation data and mRNA/microRNA expression profiles in human cancer. DNA methylation is an important epigenetic regulator of gene transcription, and genes with high levels of DNA methylation in their promoter regions are transcriptionally silent. Increasing numbers of DNA methylation and mRNA/microRNA expression profiles are being published in different public repositories. These data can help researchers to identify epigenetic patterns that are important for carcinogenesis. MethHC integrates data such as DNA methylation, mRNA expression, DNA methylation of microRNA gene and microRNA expression to identify correlations between DNA methylation and mRNA/microRNA expression from TCGA (The Cancer Genome Atlas), which includes 18 human cancers in more than 6000 samples, 6548 microarrays and 12 567 RNA sequencing data.
Assuntos
Metilação de DNA , Bases de Dados Genéticas , Neoplasias/genética , Transcriptoma , Humanos , Internet , MicroRNAs/metabolismo , Neoplasias/metabolismo , RNA Mensageiro/metabolismoRESUMO
AIM: Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS: In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 (500 mg · kg(-1) · d(-1), po) for two weeks. RESULTS: Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 (the IC50 values were 6.4, 0.69 and 5.5 nmol/L, respectively), but did not affect 18 other kinases including FGFR and PDGFR at 10 µmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilical vein endothelial cells (HUVECs), thus inhibited VEGF-induced HUVEC proliferation. DW10075 (1-100 nmol/L) dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC50 values ranging from 2.2 µmol/L (for U87-MG human glioblastoma cells) to 22.2 µmol/L (for A375 melanoma cells). In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. CONCLUSION: DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development.
Assuntos
Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Glioblastoma/tratamento farmacológico , Pirimidinas/química , Pirimidinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Galinhas , Glioblastoma/irrigação sanguínea , Glioblastoma/metabolismo , Glioblastoma/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ratos Sprague-Dawley , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
A new sesquiterpene, bakkenolide-â ¥a (1), was isolated from the rhizome of Petasites japonicas (Sieb. et Zucc.) Maxim. The structure was characterized on the basis of various NMR ((1)H, (13)C, (1)H-(1)H COSY, HMQC, HMBC and NOESY) and mass spectrometry data. Bakkenolide-â ¥a showed potent cerebral hypoxia- ischemia protective activity in mice subjected to decapitation through prolonging the survival time and gasping time. It also exhibited a protective activity against hypoxia injury in PC12 cells in anaerobic culture by inhibition of lactate dehydrogenase (LDH) release.
Assuntos
Hipóxia-Isquemia Encefálica/tratamento farmacológico , Petasites/química , Rizoma/química , Sesquiterpenos/química , Animais , Hipóxia Celular , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Células PC12 , Extratos Vegetais/química , Ratos , Sesquiterpenos/isolamento & purificaçãoRESUMO
BACKGROUND: MicroRNAs (miRNAs) simultaneously target many transcripts through partial complementarity binding, and have emerged as a key type of post-transcriptional regulator for gene expression. How miRNA accomplishes its pleiotropic effects largely depends on its expression and its target repertoire. Previous studies discovered thousands of miRNAs and numerous miRNA target genes mainly through computation and prediction methods which produced high rates of false positive prediction. The development of Argonaute cross-linked immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq) provides a system to effectively determine miRNA target genes. Likewise, the accuracy of dissecting the transcriptional regulation of miRNA genes has been greatly improved by chromatin immunoprecipitation of the transcription factors coupled with sequencing (ChIP-Seq). Elucidation of the miRNA target repertoire will provide an in-depth understanding of the functional roles of microRNA pathways. To reliably reconstruct a miRNA-mediated regulatory network, we established a computational framework using publicly available, sequence-based transcription factor-miRNA databases, including ChIPBase and TransmiR for the TF-miRNA interactions, along with miRNA-target databases, including miRTarBase, TarBase and starBase, for the miRNA-target interactions. We applied the computational framework to elucidate the miRNA-mediated regulatory network in the Mir122aâ»/â» mouse model, which has an altered transcriptome and progressive liver disease. RESULTS: We applied our computational framework to the expression profiles of miRNA/mRNA of Mir122aâ»/â» mutant mice and wild-type mice. The miRNA-mediated network involves 40 curated TFs contributing to the aberrant expression of 65 miRNAs and 723 curated miRNA target genes, of which 56% was found in the differentially-expressed genes of Mir122a--mice. Hence, the regulatory network disclosed previously-known and also many previously-unidentified miRNA-mediated regulations in mutant mice. Moreover, we demonstrate that loss of imprinting at the chromosome 12qF1 region is associated with miRNA overexpression in human hepatocellular carcinoma and stem cells, suggesting initiation of precancerous changes in young mice deficient in miR-122. A group of 9 miRNAs was found to share miR-122 target genes, indicating synergy between miRNAs and target genes by way of multiplicity and cooperativity. CONCLUSIONS: The study provides significant insight into miRNA-mediated regulatory networks. Based on experimentally verified data, this network is highly reliable and effective in revealing previously-undetermined disease-associated molecular mechanisms. This computational framework can be applied to explore the significant TF-miRNA-miRNA target interactions in any complex biological systems with high degrees of confidence.
Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Fígado/metabolismo , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/genética , Imunoprecipitação da Cromatina , Bases de Dados Genéticas , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala , Humanos , Neoplasias Hepáticas/genética , Camundongos Knockout , Modelos Genéticos , Reprodutibilidade dos Testes , Transdução de Sinais/genética , Fatores de Transcrição/genéticaRESUMO
Andrology and gynecology have a similar or the same theoretical basis in Traditional Chinese Medicine (TCM). Andrology has a history of less than 3 decades in China, while TCM gynecology has developed for over a thousand years. The development of andrology could be greatly promoted with the guidance of the theories and prescriptions of gynecology.
Assuntos
Andrologia , Ginecologia , Medicina Tradicional Chinesa , China , HumanosRESUMO
The ingredients of five kinds of Zhejiang's yellow Chrysanthemum morifolium with different flower blossoming stages were comparatively analyzed. Polysaccharides, total flavonoids, volatile oil, alcohol extract, water extract, chlorogenic acid, luteolin, 3,5-O-dicaffeoyl quinic acid and fingerprint of the ingredient were determined as indicators. During flower blossoming stages, the ingredients of Ch. morifolium showed a big difference with a certain variation. At the early opening stage, the contents of flavonoids and volatile oil were higher, the content of chlorogenic acid, luteolin, 3,5-O-dicaffeoyl quinic acid were higher in the middle of the flowers 50% -80% fowers blossoming degree is the optimal time for harvest.
Assuntos
Medicamentos de Ervas Chinesas/análise , Flores/crescimento & desenvolvimento , China , Ácido Clorogênico/análise , Cromatografia Líquida de Alta Pressão , Chrysanthemum/química , Chrysanthemum/crescimento & desenvolvimento , Flavonoides/análise , Flores/química , Controle de Qualidade , Ácido Quínico/análiseRESUMO
Surface coating of antifouling materials on the substrates offers convenient strategies and great opportunities to improve their biocompatibility and functions of host substrates for wide biomedical applications. In this work, we present a general surface zwitterionization strategy to improve surface biocompatibility and antifouling properties of titanium (Ti) by grafting zwitterionic poly(sulfobetaine methacrylate) (polySBMA). This method also demonstrates its general applicability to graft polySBMA onto Ti surface using different anchoring agents of dopamine and silane. The resulting polySBMA grafted from dopamine- (pTi-D-pSBMA) and silane-anchored titanium surfaces (pTi-Si-pSBMA) surfaces exhibit superlow fouling ability to highly resist the adhesions of plasma proteins, platelets, erythrocytes, leukocytes, human fibroblast (HT1080), E. coli, and S. epidermidis. The interfacial properties of the surface-modified Ti surfaces are analyzed and correlated with their antifouling properties. The new method and materials provide a more general, flexible, and robust way to produce an excellent nonfouling surface with adjustable interfacial structures of grafted polymers, which hopefully can be expanded to wider applications based on both the structure and surface superiorities.
Assuntos
Proteínas Sanguíneas/química , Titânio/química , Células Sanguíneas/química , Escherichia coli/química , Fibroblastos , Humanos , Propriedades de SuperfícieRESUMO
OBJECTIVE: To study the origin pre-treating and processing integration techniques of Paeonia Radix Alba. METHOD: Different processing integration techniques were adopted and compared with traditional processing techniques to determine drying rate, aqueous extracts and peoniflori content. RESULT: Half-dry slices baked at 100 degrees C for 20 min and steamed at 100 degrees C for 10 min had the highest peoniflori contents. Half-dry slices baked at 100 degrees C for 20 min had the highest content of aqueous extracts. Products processed with conventional method and sulfur-fumigation had the lowest content of aqueous extracts. CONCLUSION: The origin processing integration techniques of Paeonia Radix Alba lose less active ingredients than conventional processing methods.
Assuntos
Medicamentos de Ervas Chinesas/química , Paeonia/química , Tecnologia Farmacêutica/métodos , China , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/isolamento & purificaçãoRESUMO
Withanolide A is a biologically active secondary metabolite occuring in roots and leaves of Withania somnifera. In the present study, adventitious roots from leaf explants of W. somnifera were induced for the production of withanolide-A by Agrobacterium tumefaciens strain C58C1 to obtain hair roots. Hair roots induction rate reached 30%. The withanolide A was determined by HPLC in different hair roots lines and different parts of W. somnifera. The average content of withanolide A in all hair roots lines were 1.96 times as high as that in wild-plant, the concentration of withanolide A in hair roots (1.783 mg x g(-1) dry weight) were 1.51 times as high as the roots of wild W. somnifera (1.180 mg x g(-1) dry weight), respectively. It is possible to obtain withanolide A from hair roots culture of W. somnifera.
Assuntos
Extratos Vegetais/biossíntese , Withania/metabolismo , Vitanolídeos/metabolismo , Agrobacterium tumefaciens/fisiologia , Extratos Vegetais/análise , Raízes de Plantas/química , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Withania/química , Withania/crescimento & desenvolvimento , Withania/microbiologia , Vitanolídeos/análiseRESUMO
OBJECTIVE: To study the condition of plant regeneration and clonal propagation system of Datura metel. METHODS: Stems and leaves of Datura metel were used as explants, effects of different hormones for callus induction and plant regeneration of leaves and clonal propagation system of stems were studied and optimized. RESULTS: The optimal way to obtain sterile explant for leaves were sterilized in 75% ethyl alcohol for 6 s then 0.1% HgCl2 for 6 min; Stems were sterilized in 75% ethyl alcohol for 8 s then 0.1% HgCl2 for 7 min. The optimal medium for callus of leaves was MS + 1.0 mg/L 6-BA + 0.1 mg/L NAA; The optimal medium for callus induction of clustered buds was MS + 2.0 mg/L 6-BA + 0.2 mg/L NAA; The optimal medium for clonal propagation system of stems was MS + 3.0 mg/L 6-BA + 0.05 mg/L NAA. The best medium for rooting induction was MS + 0.5 mg/L IBA. Transplant survival rate of plantlet was greater than 90% in humus soil-pearlite (5:1). CONCLUSION: The condition of plant regeneration and clonal propagation system of Datura metel is established.
Assuntos
Datura metel/crescimento & desenvolvimento , Plantas Medicinais/crescimento & desenvolvimento , Regeneração/efeitos dos fármacos , Técnicas de Cultura de Tecidos/métodos , Meios de Cultura/química , Meios de Cultura/farmacologia , Datura metel/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Caules de Planta/efeitos dos fármacos , Caules de Planta/crescimento & desenvolvimento , Plantas Medicinais/efeitos dos fármacosRESUMO
A new, validated method, developed for the simultaneous determination of 16 phenolics (chlorogenic acid, scopoletin, vitexin, rutin, afzelin, isoquercitrin, narirutin, kaempferitrin, quercitrin, quercetin, kaempferol, chrysosplenol D, vitexicarpin, 5-hydroxy-3,3',4',7-tetramethoxy flavonoids, 5-hydroxy-3,4',6,7-tetramethoxy flavonoids and kaempferol-3,7,4'-trimethyl ether) in Houttuynia cordata Thunb. was successfully applied to 35 batches of samples collected from different regions or at different times and their total antioxidant activities (TAAs) were investigated. The aim was to develop a quality control method to simultaneously determine the major active components in H. cordata. The HPLC-DAD method was performed using a reverse-phase C18 column with a gradient elution system (acetonitrile-methanol-water) and simultaneous detection at 345 nm. Linear behaviors of method for all the analytes were observed with linear regression relationship (r(2)>0.999) at the concentration ranges investigated. The recoveries of the 16 phenolics ranged from 98.93% to 101.26%. The samples analyzed were differentiated and classified based on the contents of the 16 characteristic compounds and the TAA using hierarchical clustering analysis (HCA) and principal component analysis (PCA). The results analyzed showed that similar chemical profiles and TAAs were divided into the same group. There was some evidence that active compounds, although they varied significantly, may possess uniform anti-oxidant activities and have potentially synergistic effects.
Assuntos
Houttuynia/química , Antioxidantes/análise , Compostos de Bifenilo/química , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Flavonoides/análise , Indicadores e Reagentes , Fenóis/análise , Picratos/química , Análise de Componente Principal , Controle de Qualidade , Padrões de Referência , Análise de Regressão , Reprodutibilidade dos Testes , Soluções , Solventes , Espectrofotometria Ultravioleta/métodosRESUMO
The widespread adoption of genetically modified (GM) crops has escalated concerns about their safety and ethical implications, underscoring the need for efficient GM crop detection methods. Conventional detection methods, such as polymerase chain reaction, can be costly, lab-bound, and time-consuming. To overcome these challenges, we have developed RapiSense, a cost-effective, portable, and sensitive biosensor platform. This sensor generates a measurable voltage shift (0.1-1â¯V) in the system's current-voltage characteristics, triggered by an increase in membrane's negative charge upon hybridization of DNA/RNA targets with a specific DNA probe. Probes designed to identify the herbicide resistance gene hygromycin phosphotransferase show a detection range from â¼1â¯nM to â¼10 µM and can discriminate between complementary, non-specific, and mismatched nucleotide targets. The incorporation of a small membrane sensor to detect fragmented RNA samples substantially improve the platform's sensitivity. In this study, RapiSense has been effectively used to detect specific DNA and fragmented RNA in transgenic variants of Arabidopsis, sweet potato, and rice, showcasing its potential for rapid, on-site GM crop screening.