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1.
Med Sci Monit ; 26: e922676, 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32533823

RESUMO

BACKGROUND The aim of this study was to explore a comprehensive analysis of the competing endogenous (ceRNA) network of lung adenocarcinoma and predict its regulatory mechanism and prognosis correlation based on The Cancer Genome Atlas (TCGA) database. MATERIAL AND METHODS The genes expression data from 535 lung adenocarcinoma cases and 59 normal tissue cases were acquired and downloaded from TCGA database, and differentially expressed messenger RNA (mRNA), long noncoding RNA (lncRNA) and microRNA (miRNA) were selected primarily by "edgeR" package in R software, which further constructs lncRNA-miRNA-mRNA ceRNA network. We then proceed to carry out Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Kaplan-Meier survival analysis of the mRNAs involved in the ceRNA network. RESULTS There are 3 mRNAs (ANLN, IGFBP1, and TFAP2A) in differentially expressed genes, 4 lncRNAs (AC015923.1, FGF12-AS2, LINC00211, and MED4-AS1), and 2 miRNAs (miR-31 and miR-490) associated with the prognostic of lung adenocarcinoma. Besides, LINC00461 and has-mir-139 as key nodes were found in the ceRNA network. Significantly, miR-31 shows the greatest prognostic value related to the adverse effect of the prognostic of lung adenocarcinoma (P<0.001). CONCLUSIONS By analyzing the expression data of lung adenocarcinoma in TCGA database, we found that 3 mRNAs, 4 lncRNAs, and 2 miRNAs were screened as potential prognostic factors for lung adenocarcinoma. In addition, LINC00461 and has-mir-139 are 2 important regulatory network nodes in lung adenocarcinoma ceRNA.

2.
BMC Genomics ; 21(1): 49, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941462

RESUMO

BACKGROUND: Clinopodium gracile (Benth.) Matsum (C. gracile) is an annual herb with pharmacological properties effective in the treatment of various diseases, including hepatic carcinoma. Triterpenoid saponins are crucial bioactive compounds in C. gracile. However, the molecular understanding of the triterpenoid saponin biosynthesis pathway remains unclear. RESULTS: In this study, we performed RNA sequencing (RNA-Seq) analysis of the flowers, leaves, roots, and stems of C. gracile plants using the BGISEQ-500 platform. The assembly of transcripts from all four types of tissues generated 128,856 unigenes, of which 99,020 were mapped to several public databases for functional annotation. Differentially expressed genes (DEGs) were identified via the comparison of gene expression levels between leaves and other tissues (flowers, roots, and stems). Multiple genes encoding pivotal enzymes, such as squalene synthase (SS), or transcription factors (TFs) related to triterpenoid saponin biosynthesis were identified and further analyzed. The expression levels of unigenes encoding important enzymes were verified by quantitative real-time PCR (qRT-PCR). Different chemical constituents of triterpenoid saponins were identified by Ultra-Performance Liquid Chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). CONCLUSIONS: Our results greatly extend the public transcriptome dataset of C. gracile and provide valuable information for the identification of candidate genes involved in the biosynthesis of triterpenoid saponins and other important secondary metabolites.


Assuntos
Magnoliopsida/genética , Saponinas/biossíntese , Transcriptoma , Triterpenos/metabolismo , Vias Biossintéticas/genética , Farnesil-Difosfato Farnesiltransferase/química , Magnoliopsida/enzimologia , Magnoliopsida/metabolismo , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Saponinas/química , Metabolismo Secundário/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triterpenos/química
3.
Parasitology ; 147(1): 58-64, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31556865

RESUMO

It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P ⩽ 0.05) at the doses of 4.4, 8.8, 17.6 µmol (kg·d)-1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.

4.
IEEE Trans Nanobioscience ; 19(2): 173-182, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31831430

RESUMO

A highly sensitive and selective optical fiber-based enzymatic biosensor has been proposed in the present study for detection of uric acid (UA) in human serum. The working mechanism of sensor depends on surface plasma property and localized surface plasmon resonance technique. For this purpose, a micro-ball fiber sensor probe of [Formula: see text] diameter was fabricated using advanced fusion-splicer and coated with gold nanoparticles (AuNPs) and graphene oxide (GO) in order to enhance its sensitivity. UV-Visible spectrophotometer and high-resolution transmission electron microscope (HR-TEM) were used to characterize the AuNPs solution and GO aqueous dispersion. The absorbance spectrum of AuNPs and GO are recorded at 519 nm and 230 nm, respectively. The coating of AuNPs and GO over fiber surface were verified by using a scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX). Thereafter, sensor probe was functionalized with the specific enzyme i.e. uricase for the UA detection. The linearity response of uricase/GO/AuNPs-coated micro-ball optical fiber sensor is reported in the range of [Formula: see text]-1 mM UA concentrations. The reflectance of sensor linearly decreases with the increasing UA concentrations. Sensitivity of the sensor is 2.1 %/mM with a good slope of linearity with detection limit of [Formula: see text]. To test the accuracy of proposed sensor, UA concentration in serum samples have also tested by using proposed sensor and A5800 Automatic Biochemical Analyzer. The results of the developed sensor are consistent with the results of A5800 Automatic Biochemical Analyzer. Thus, proposed sensor can be successfully utilized for UA detection in human serum samples.

5.
Bioelectrochemistry ; 131: 107352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31494386

RESUMO

The designed synthesis of efficient materials can significantly enhance the performance of electrochemical immunoassay in the detection of diseases, pesticide residues and environmental pollutants. The hollow AgPt@Pt core-shell nanoparticles (AgPt@Pt HNs) have exhibited high catalytic efficiency to the hydrogen peroxide (H2O2) reduction for its high mass activity from their hollow structure. Their limitation of instability can be overcome by loading on polypyrrole nanosheet (PPy NS). Besides, PPy NS exhibits good conductivity, and there exists environmentally-friendly method for its synthetic. Thus, AgPt@Pt HNs loaded on PPy NS (AgPt@Pt HNs/PPy NS) exhibits high catalytic efficiency to the reduction of H2O2 and good stability. Furthermore, the quick electron transfer of AgPt@Pt HNs/PPy NS modified glassy carbon electrode has been evidenced by the finding that the large constant of apparent electron transfer rate has also enlarged the current signal when the amount of electron is invariant. The modified electrode has fabricated a label-free amperometric immunosensor to detect sensitively prostate-specific antigen (PSA) with H2O2 as the electroactive material. The immunosensor in hollow core-shell nanosheet structure exhibiting good detection performance of PSA shows its promising applications in the clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Eletrodos , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Platina/química , Polímeros/química , Pirróis/química , Biomarcadores Tumorais/análise , Catálise , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredução , Antígeno Prostático Específico/análise
6.
Biosens Bioelectron ; 142: 111580, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31422222

RESUMO

Medically, the dynamic change of carcinoembryonic antigen (CEA) concentration has been an important indicator for monitoring and diagnosing tumors. The sensitive and early detection of CEA plays a momentous role in the prevention and diagnosis of cancer and the evaluation of treatment efficiency. In this work, a sensitive sandwich-type electrochemical immunosensor was fabricated for the quantitative detection of CEA. The trimetallic yolk-shell Au@AgPt nanocubes (Au@AgPt YNCs) loaded on amino-functionalized MoS2 nanoflowers (MoS2 NFs/Au@AgPt YNCs) were used as the labels to conjugate with secondary antibodies. The Au@AgPt YNCs with internal space and permeable shell improved catalytic active surface area. The nanosheet-based MoS2 NFs with good catalytic activity were used as carriers to load Au@AgPt YNCs effectively. Due to the biphasic synergistic catalysis, MoS2 NFs/Au@AgPt YNCs catalyzed the reduction of H2O2 effectually to amplify the current signal. Besides, Au triangular nanoprisms (Au TNPs) were used as substrate material to increase the effective contact areas with the surface of electrode and accelerate the interface electron transfer. Under the optimal conditions, a broad linear range from 10 fg mL-1 to 100 ng mL-1 with low detection limit of 3.09 fg mL-1 (S/N = 3) for detecting CEA was obtained. Moreover, the detection results of the human serum samples were satisfactory, indicating the fabricated immunosensor had potential application values in the early clinical analysis.


Assuntos
Técnicas Biossensoriais/métodos , Antígeno Carcinoembrionário/sangue , Dissulfetos/química , Nanopartículas Metálicas/química , Molibdênio/química , Anticorpos Imobilizados/química , Técnicas Eletroquímicas/métodos , Ouro/química , Humanos , Imunoensaio/métodos , Limite de Detecção , Platina/química , Prata/química
7.
Mol Med Rep ; 20(3): 2851-2858, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322188

RESUMO

Glucocorticoids are the most common cause of glucocorticoid­induced osteoporosis (GIOP). Moreover, the role of circular RNAs (circRNAs) in the regulation of bone metabolism remains unclear. Therefore, in the present study, it was hypothesized that hsa_circ_0006393 may play an important role in GIOP. To investigate the role of circRNAs in GIOP, treatment with dexamethasone or transfection with a vector overexpressing hsa_circ_0006393 were performed using in vitro cell and in vivo mouse models. Reverse transcription­quantitative PCR, fluorescence in situ hybridization and western blotting were performed to investigate the function of hsa_circ_0006393 in vitro. In addition, the effects of hsa_circ_0006393 on osteogenesis were investigated. Dual­energy X­ray absorptiometry analysis was performed to examine the osteogenic potential of hsa_circ_0006393 in vivo. Moreover, the mechanism underlying hsa_circ_0006393­mediated bone metabolism regulation via the microRNA (miR)­145­5p/forkhead box O1 (FOXO1) pathway was investigated. The present results suggested that the expression level of hsa_circ_0006393 was decreased in patients with GIOP. Furthermore, the overexpression of hsa_circ_0006393 increased the expression level of genes associated with osteogenesis. Moreover, hsa_circ_0006393 was identified to be localized mainly in the cytoplasm and nucleus of bone marrow mesenchymal stem cells. miR­145­5p was found to be directly targeted by hsa_circ_0006393. Collectively, hsa_circ_0006393 increases the expression levels of osteogenic genes during bone remodeling by sponging miR­145­5p and upregulating FOXO1.


Assuntos
Proteína Forkhead Box O1/genética , MicroRNAs/genética , Osteogênese , Osteoporose/genética , RNA Circular/genética , Adulto , Idoso , Animais , Células Cultivadas , Regulação para Baixo , Feminino , Glucocorticoides , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Osteoporose/fisiopatologia , Regulação para Cima
8.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1799-1807, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342705

RESUMO

Chalcone synthase( CHS) and chalcone isomerase( CHI) are key enzymes in the biosynthesis pathway of flavonoids. In this study,unigenes for CHS and CHI were screened from the transcriptome database of Arisaema heterophyllum. The open reading frame( ORFs) of chalcone synthase( Ah CHS) and chalcone isomerase( Ah CHI) were cloned from the plant by RT-PCR. The physicochemical properties,expression and structure characteristics of the encoded proteins Ah CHS and Ah CHI were analyzed. The ORFs of Ah CHS and Ah CHI were 1 176,630 bp in length and encoded 392,209 amino acids,respectively. Ah CHS functioned as a symmetric homodimer. The N-terminal helix of one monomer entwined with the corresponding helix of another monomer. Each CHS monomer consisted of two structural domains. In particular,four conserved residues define the active site. The tertiary structure of Ah CHI revealed a novel open-faced ß-sandwich fold. A large ß-sheet( ß4-ß11) and a layer of α-helices( α1-α7) comprised the core structure. The residues spanning ß4,ß5,α4,and α6 in the three-dimensional structure were conserved among CHIs from different species. Notably,these structural elements formed the active site on the protein surface,and the topology of the active-site cleft defined the stereochemistry of the cyclization reaction. The homology comparison showed that Ah CHS had the highest similarity to the CHS of Anthurium andraeanum,while Ah CHI had the highest similarity to the CHI of Paeonia delavayi. This study provided the basis for the functional study of Ah CHS and Ah CHI and the further study on plant flavonoid biosynthesis pathway.


Assuntos
Aciltransferases/genética , Arisaema/enzimologia , Liases Intramoleculares/genética , Proteínas de Plantas/genética , Aciltransferases/química , Arisaema/genética , Clonagem Molecular , Liases Intramoleculares/química , Proteínas de Plantas/química
9.
Zhongguo Zhong Yao Za Zhi ; 44(7): 1321-1326, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090287

RESUMO

Through market investigation, the adulteration of Zaocys dhumnades on markets was found out, and samples of authentic and adulterated Z. dhumnades on markets were collected. The origin and properties of the adulterated Z. dhumnades were studied in order to provide reference for the identification of Z. dhumnades. The counterfeit Z. dhumnades sold on markets were as follows: Ptyas korros, P. mucosus, Najanaja atra, Sinonatrix annularis, Dinodon septentrionalis, etc. It is found that there existed a obvious difference between the traits of the Z. dhumnades and counterfeits. Genuine Z. dhumnades with "sword ridge" "iron tail", strongly ribbed scales and other features, is the key point to identify the difference from adulterants.


Assuntos
Contaminação de Medicamentos , Materia Medica/normas , Serpentes , Animais
10.
J Cell Physiol ; 234(7): 11805-11821, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30714135

RESUMO

Lung adenocarcinoma (LAD) is the leading cause of cancer death worldwide. Long noncoding RNAs (lncRNAs) have been shown to play an important regulatory role in cancer biology, including that of LAD. The aim of this experiment was to explore the interaction of LINC00483, microRNA-144 (miR-144), and homeobox A10 (HOXA10), and their effects on radio sensitivity and epithelial-mesenchymal transition (EMT) of LAD. Initially, microarray analysis was used to screen out miRNAs and lncRNAs, as well as the differentially expressed genes related to LAD. Following the screening process, the targeting relationship of LINC00483, miR-144, and that of miR-144 and HOXA10 was determined. Following that, the expression of LINC00483, miR-144, messenger RNA (mRNA), as well as protein expression of HOXA10, MMP-2, MMP-9, E-cadherin, vimentin, and N-cadherin that followed in cells was determined. Also, the effect of LINC00483 on cell migration and invasion ability, and cell tumorigenic ability was detected. LINC00483 and HOXA10 were found to be upregulated whereas miR-144 was downregulated in LAD. Silencing of LINC00483 could competitively bind to miR-144, thereby upregulating HOXA10. LINC00483 or HOXA10 silencing led to decreased HOXA10, MMP-2, MMP-9, vimentin, and N-cadherin but elevated miR-144 and E-cadherin. Moreover, after being transfected with silenced LINC00483, the cell proliferation, migration, and invasion were inhibited with enhanced radiosensitivity. Consequently, the data of the study indicates that interference of LINC00483 weakens its competitive binding ability to miR-144, thus reducing HOXA10 expression, and enhancing radiosensitivity in LAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Transição Epitelial-Mesenquimal/genética , Proteínas Homeobox A10/metabolismo , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Animais , Sequência de Bases , Ligação Competitiva , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Masculino , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Modelos Biológicos , Invasividade Neoplásica , Regulação para Cima/genética
11.
Bioelectrochemistry ; 126: 92-98, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30530260

RESUMO

In this work, a sandwich-type electrochemical immunosensor was fabricated to quantitatively detect hepatitis B surface antigen (HBsAg). The immunosensor was based on Rh core and Pt shell nanodendrites loaded onto amino group functionalized graphene nanosheet (RhPt NDs/NH2-GS) as label and gold nanoparticles loaded onto polypyrrole nanosheet (Au NPs/PPy NS) as platform. RhPt NDs with abundant catalytic active sites because of the branched core-shell structure, RhPt NDs/NH2-GS as the label displayed high catalytic activity, amplifying the current signal of the immunosensor. Additionally, Au NPs/PPy NS enhanced the electron transfer and provided a good microenvironment to immobilize antibodies effectively, thus improving the sensitivity of the immunosensor. Based on above advantages, the immunosensor emerged a linear concentration ranging from 0.0005 to 10 ng/mL, a low detection limit of 166 fg/mL for HBsAg (S/N = 3) and good stability, selectivity, reproducibility. Furthermore, the satisfactory accuracy in analysis of actual serum samples implied the immunosensor had promising prospect in clinical analysis applications.


Assuntos
Anticorpos Imobilizados/química , Técnicas Eletroquímicas/métodos , Antígenos de Superfície da Hepatite B/sangue , Nanoestruturas/química , Polímeros/química , Pirróis/química , Técnicas Biossensoriais/métodos , Ouro/química , Grafite/química , Hepatite B/sangue , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Imunoensaio/métodos , Limite de Detecção , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanoestruturas/ultraestrutura , Platina/química , Ródio/química
12.
Sci Rep ; 8(1): 17643, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518768

RESUMO

Arisaema heterophyllum Blume (AhBl) is one of the valued medicinal plants. However, its genetic information is limited, which impedes further studies of this valuable resource. To investigate the genes involved in the isoflavonoid biosynthesis, we deeply performed transcriptome sequencing for AhBl. An average of 10.98 Gb clean reads were obtained based on root, tuber and leaf tissues, and 109,937 unigenes were yielded after de novo assembly. In total, 72,287 of those unigenes were annotated in at least one public database. The numbers of expressed unigenes in each tissue were 35,686, 43,363 and 47,783, respectively. The overall expression levels of transcripts in leaf were higher than those in root and tuber. Differentially expressed genes analysis indicated that a total of 12,448 shared unigenes were detected in all three tissues, 10,215 of which were higher expressed in tuber than that in root and leaf. Besides, 87 candidate unigenes that encode for enzymes involved in biosynthesis of isoflavonoid were identified and analyzed, and some key enzyme genes were experimentally validated by quantitative Real-Time PCR (qRT-PCR). This study provides a unique dataset for the systematic analysis of AhBl functional genes and expression characteristics, and facilitates the future study of the pharmacological mechanism of AhBl.


Assuntos
Arisaema/genética , Isoflavonas/genética , Proteínas de Plantas/genética , Transcriptoma , Arisaema/metabolismo , Vias Biossintéticas , Perfilação da Expressão Gênica , Ontologia Genética , Genes de Plantas , Isoflavonas/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Tubérculos/genética , Tubérculos/metabolismo
13.
J Cell Physiol ; 233(11): 8617-8629, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29761857

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder due to the loss of dopaminergic neurons in the substantia nigra. This study focuses on the effect of microRNA-329 (miR-329) on nigral dopaminergic neurons in a rat model of PD via the FoxO3a signaling pathway by binding to CDKN2D. Brain tissues from the substantia nigra were taken from the rats in two groups. TUNEL staining was used to observe tyrosine hydroxylase (TH)-positive neurons. Nigral dopaminergic neurons were randomized into the normal, blank, negative control (NC), miR-329 mimics, miR-329 inhibitors, small interfering (siRNA)-CDKN2D, and miR-329 inhibitors + siRNA-CDKN2D groups. Expressions of miR-329, CDKN2D, FoxO3a, AKT, caspase-3 and Bcl-2 were determined using RT-qPCR and western blotting. Apoptosis rate of nigral dopaminergic neurons in 7 groups was determined by flow cytometry. Compared with the blank and NC groups, the miR-329 mimics group showed increased miR-329 and caspase-3 expressions as well as decreased expressions of CDKN2D, FoxO3a, AKT, and Bcl-2, the siRNA-CDKN2D group indicated enhanced expressions of caspase-3 and declined expressions of CDKN2D, FoxO3a, AKT, and Bcl-2, and the miR-329 inhibitors group revealed decreased miR-329 and caspase-3 expressions and increased expressions of CDKN2D, FoxO3a, AKT, and Bcl-2. The apoptosis rate of nigral dopaminergic neurons was significantly increased in the miR-329 mimics and siRNA-CDKN2D groups, but was decreased in the miR-329 inhibitors group. Our data suggested that downregulated miR-329 could inhibit apoptosis of nigral dopaminergic neurons in a rat model of PD by upregulating the expression of CDKN2D via the activation of the FoxO3a signaling pathway.


Assuntos
Inibidor de Quinase Dependente de Ciclina p19/genética , Proteína Forkhead Box O3/genética , MicroRNAs/genética , Doença de Parkinson/genética , Animais , Apoptose/genética , Caspase 3/genética , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Regulação da Expressão Gênica , Humanos , MicroRNAs/antagonistas & inibidores , Doença de Parkinson/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/genética , Ratos , Transdução de Sinais , Substância Negra/metabolismo , Substância Negra/patologia
14.
Zhongguo Zhong Yao Za Zhi ; 42(3): 510-516, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28952257

RESUMO

Eighteen compounds were isolated from the 95% ethanol extract of fresh tubers of Dioscorea bulbifera by column chromatography over silica gel,Sephadex LH-20, and ODS. Their structures were elucidated by spectroscopic data analysis as 6-hydroxy-2,10,10-trimethoxy-anthracen-9-one(1), diosgenin (2), stigmasterol(3), 3, 7-dimethoxy-5, 3', 4'-trihydroxyflavone(4), 2, 7-dihydroxy-3, 4-dimethoxyphenanthrene(5), 3, 7-dihydroxy-2, 4-dimethoxy phenanthrene(6), 2, 7-dihydroxy-4-methoxyphenanthrene (7), 2, 7-dihydroxy-3, 4-dimethoxy-9, 10-dihydroxy phenanthrene(8), azelaic acid (9), 8-epidiosbulbin E acetate (10), 1, 7-bis-(4-hydroxyphenyl)-4E, 6E-heptadien-3-one(11), diosbulbin B(12), pentacosanoic acid 2', 3'-dihydroxypropyl ester(13), 2, 7-dihydroxy-4-methoxy-9, 10-dihydroxy-phenanthrene (14), 1, 7-bis-(4-hydroxyphenyl)-1E, 4E, 6E-heptatrien-3-one (15), 6-ethoxy-1H-pyrimidine-2, 4-dione (16), 3, 5, 4'-trihydroxy-bibenzyl (17), and diosbulbin F (18). Compound 1 is a new compound, and compounds 7, 9, 13, and 16 were isolated from this plant for the first time.


Assuntos
Dioscorea/química , Compostos Fitoquímicos/análise , Tubérculos/química
15.
Zhongguo Zhong Yao Za Zhi ; 42(13): 2606-2611, 2017 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28840706

RESUMO

Both Patrinia Herba and Patrinia Radix are traditional Chinese herbal medicines. The herbal source and medicinal part of them are confusing in the herbal medicine market of China. To explore the evolution and transition of the herbal source and medicinal part of Patrinia Herba and Patrinia Radix, this paper systematically summarizes the record of the herbal source and medicinal part of them in ancient classics of herbal medicine in China. According to the findings, before Ming Dynasty, Patrinia Herba originated from the radix of the plants with yellow flowers of Patrinia. In Ming and Qing Dynasty, Patrinia Herba originates from the whole plant (including the radix)of the plant with white flowers of Patrinia. In Ming Dynasty, Patrinia Radix, stemming from the radix of the plants with yellow flowers of Patrinia, started to be used as a traditional Chinese herbal medicine, which had the same herbal source with that of Patrinia Herba before Ming Dynasty. Therefore, Patrinia Herba and Patrinia Radix can be seen as the same traditional Chinese herbal medicine, and the genuine of Patrinia Herba should be the radix and the whole herba of P. scabiosaefolia and P. heterophylla.


Assuntos
Medicamentos de Ervas Chinesas/história , Patrinia/química , Raízes de Plantas/química , China , História Antiga , Medicina Tradicional Chinesa , Plantas Medicinais/química
16.
Hortic Res ; 4: 17024, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28638623

RESUMO

Willow (Salix) is one of the most important ornamental tree species in landscape plants. One species, Salix matsudana, is widely used as a shade tree and border tree because of its soft branches and plump crown. Some varieties of S. matsudana were salt tolerant and could grow normally in coastal regions. However, the molecular mechanisms of salt tolerance for S. matsudana have been less clear. Here, we addressed this issue by performing a mapping experiment containing 195 intraspecific F1 progeny of S. matsudana, derived from salt-sensitive 'yanjiang' and salt-tolerant '9901', grown by cuttings in a 100 mM NaCl solution. Growth performance of these progeny under salt stress was investigated, displaying marked genotypic variability with the coefficients of variance of 28.64-86.11% in shoot and root growth traits. We further mapped specific QTLs contributing to these differences to the Salix genome. Of the 204 QTLs identified, a few were detected to explain a remarkably larger portion of the phenotypic variation than many others. Many detected QTLs were found to reside in the region of candidate genes of known biological function. The discovery of growth QTLs expressed under salt stress provides important information for marker-assisted breeding of salt tolerant Salix varieties and founds the basis for the application of S. matsudana in coastal afforestation.

17.
J Nat Prod ; 80(6): 1742-1749, 2017 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-28548825

RESUMO

Nepetaefolins A-J (1-10) and seven known compounds were isolated from the whole plant of Caryopteris nepetaefolia. The absolute configurations of 1-3 were determined from single-crystal X-ray diffraction and spectroscopic data. Compounds 6 and 7, with IC50 values of 6.3-9.0 µM, showed higher cytotoxicity than paclitaxel in one non-small-cell lung cancer, patient-derived xenograft (PDX) model when tested using PDX models and the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA).


Assuntos
Abietanos/isolamento & purificação , Abietanos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Verbenaceae/química , Abietanos/química , Antineoplásicos Fitogênicos/química , Cristalografia por Raios X , Diterpenos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Humanos , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
18.
Oncotarget ; 8(10): 16259-16274, 2017 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-28187444

RESUMO

Idelalisib is a targeted agent that potently inhibits PI3Kδ which is exclusively expressed in hematological cells. Bendamustine is a well-tolerated cytotoxic alkylating agent which has been extensively used for treatment of chronic lymphocytic leukemia (CLL). Both these agents are FDA-approved for CLL. To increase the potency of idelalisib and bendamustine, we tested their combination in primary CLL lymphocytes. While each compound alone produced a moderate response, combination at several concentrations resulted in synergistic cytotoxicity. Idelalisib enhanced the bendamustine-mediated DNA damage/repair response, indicated by the phosphorylation of ATM, Chk2, and p53. Each drug alone activated γH2AX but combination treatment further increased the expression of this DNA damage marker. Compared with the control, idelalisib treatment decreased global RNA synthesis, resulting in a decline of early-response and short-lived MCL1 transcripts. In concert, there was a decline in total Mcl-1 protein in CLL lymphocytes. Isogenic mouse embryonic fibroblasts lacking MCL1 had higher sensitivity to bendamustine alone or in combination compared to MCL1 proficient cells. Collectively, these data indicate that bendamustine and idelalisib combination therapy should be investigated for treating patients with CLL.


Assuntos
Cloridrato de Bendamustina/farmacologia , Dano ao DNA , Purinas/farmacologia , Quinazolinonas/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Embrião de Mamíferos/citologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Immunoblotting , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Camundongos Knockout , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
19.
Clin Cancer Res ; 23(1): 181-192, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27342398

RESUMO

PURPOSE: PI3K is a critical node in the B-cell receptor pathway, which is responsible for survival and proliferation of B-cell malignancies. Idelalisib, a PI3Kδ-isoform-specific inhibitor, has been approved to treat B-cell malignancies. Although biological activity of the drug has been evaluated, molecular mechanisms and signaling pathway disruption leading to the biological effects of idelalisib are not yet well defined. Prior laboratory reports have identified transcription and translation as the primary events for attenuation of PI3Kα isoform. We hypothesized that PI3Kδ-isoform inhibition by idelalisib should also affect gene transcription and protein translation. EXPERIMENTAL DESIGN: Using three mantle cell lymphoma cell lines and primary cells from patients, biological consequences such as apoptosis/cell-cycle analysis, as well as RNA/protein synthesis were evaluated. Proteomics analyses (RPPA and immunoblot assays) defined molecular events downstream of PI3K/AKT cassette. RESULTS: Idelalisib treatment resulted in inhibition of protein synthesis, which correlated with reduction in cell size and cell growth. A moderate loss of viability without any change in cell-cycle profile was observed. Idelalisib treatment inhibited AKT activation, an immediate downstream PI3K effector, and also reduced phosphorylation levels of downstream AKT/mTOR pathway proteins such as PRAS40. In addition, idelalisib treatment impeded activation of the MAPK pathway, and MEK, ERK and p90RSK phosphorylation levels were reduced. Reduction in AKT, PDK1, and MEK phosphorylation correlated with protein synthesis inhibition. CONCLUSIONS: Collectively, these results clarify the molecular mechanisms of actions and may provide biomarkers and targets for combination with idelalisib in B-cell malignancies. Clin Cancer Res; 23(1); 181-92. ©2016 AACR.


Assuntos
Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Biossíntese de Proteínas/efeitos dos fármacos , Purinas/farmacologia , Quinazolinonas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Modelos Biológicos , Fosfatidilinositol 3-Quinases/metabolismo , Proteômica/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Cell Biochem ; 118(9): 2625-2634, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27933650

RESUMO

This study aims to explore how microRNA-133a (miR-133a) affects cell apoptosis and radio-sensitivity by targeting EGFR via regulating MEK/ERK pathway in esophageal cancer (EC). A total of 358 EC patients were selected and assigned into the resistant and sensitive groups. Human EC KYSE 150 cell line was assigned into the blank, negative control (NC), miR-133a mimic, miR-133a inhibitors, si-EGFR, miR-133a inhibitors + si-EGFR groups after transfection. MiR-133a and EGFR mRNA expressions were detected by qRT-PCR and EGFR, MEK/ERK pathway-related protein expressions were detected by Western blotting. The radio-sensitivity and cell apoptosis were testified by clone formation and flow cytometry. MiR-133a was up-regulated but EGFR was down-regulated in the sensitive group than in the resistant group. Compared with the blank and NC groups, the miR-133a mimic and si-EGFR groups exhibited increased cell apoptosis rate but decreased EGFR, p-MEK1/2, and p-ERK1/2 protein expressions; while opposite trend was observed in the miR-133a inhibitors group. Compared with the miR-133a inhibitors group, the miR-133a inhibitors + si-EGFR group presented reduced cell survival rate, EGFR, p-MEK1/2, and p-ERK1/2 protein expressions but increased cell apoptosis rate. These results indicated that miR-133a could inhibit the MEK/ERK pathway to promote cell apoptosis and enhance radio-sensitivity by targeting EGFR in EC. J. Cell. Biochem. 118: 2625-2634, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Apoptose , Receptores ErbB/metabolismo , Neoplasias Esofágicas , Sistema de Sinalização das MAP Quinases , MicroRNAs/biossíntese , Proteínas de Neoplasias/metabolismo , RNA Neoplásico/biossíntese , Tolerância a Radiação , Regulação para Cima , Idoso , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , RNA Neoplásico/antagonistas & inibidores , RNA Neoplásico/genética
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