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1.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4145-4149, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467726

RESUMO

With repeated silica gel, octadecyl silica(ODS), and Sephadex LH-20 column chromatography, normal-phase and reverse-phase high performance liquid chromatography(HPLC), etc., a pair of new enantiomers and 5 known compounds were separated from the 95% ethanol extract of Chloranthus multistachys. These compounds were identified by the nuclear magnetic resonance spectroscopy(including 1 D-NMR and 2 D-NMR), single-crystal X-ray diffraction, circular dichroism(CD) spectroscopy, mass spectrometry(MS), and some other methods as(1R,4R,5R,8S,10R)-chloraeudolide H(1 a),(1S,4S,5S,8R,10S)-chloraeudolide H(1 b), hydroxyisogermafurenolide(2), 4α-hydroxy-5α,8ß(H)-eudesm-7(11)-en-8,12-olide(3), chloraniolide A(4), chlorantene D(5), 4α,8ß-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide(6). Compounds 1 a and 1 b are a pair of new eudesmane-type sesquiterpene enantiomers, and compounds 2-4 were isolated from C. multistachys for the first time.


Assuntos
Sesquiterpenos , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Estereoisomerismo
2.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3789-3796, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472251

RESUMO

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.


Assuntos
Diterpenos , Sesquiterpenos , Compostos Fitoquímicos/farmacologia , Plantas , Sesquiterpenos/farmacologia , Terpenos
3.
Zhongguo Zhong Yao Za Zhi ; 46(8): 2067-2071, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982521

RESUMO

Eight sesquiterpenes were isolated and purified from the ethanol extract of Chloranthus henryi by column chromatographies over silica gel, ODS and Sephadex LH-20,and preparative HPLC. Their chemical structures were established by spectral data and physiochemical properties as(1S,6S,8S,10R)-8-ethoxy-10-methoxychlomultin C(1),tianmushanol(2),multistalide A(3),myrrhterpenoid N(4),1α,9α-dihydroxy-8,12-expoxy-eudesma-4,7,11-trien-6-one(5),4ß,10α-aromadendranediol(6),oplopanone(7),10α-hydroxycadinan-4-en-3-one(8). Among them, compound(1) was a new compound, and compounds 2-8 were isolated from Chloranthus henryi for the first time.


Assuntos
Sesquiterpenos , Cromatografia Líquida de Alta Pressão , Estrutura Molecular
4.
Nat Prod Res ; : 1-8, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044699

RESUMO

Phytochemical investigation on the whole plant of Chloranthus multistachys pei (Chloranthaceae) afforded three pairs of new sesquiterpene enantiomers (+)/(-)-chlorantene M [(+)/(-)-1], (+)/(-)-chlorantene M1 [(+)/(-)-2] and (+)/(-)-chlorantene N [(+)/(-)-3]. The structures of new compounds were determined through spectroscopic techniques (HR-ESI-MS, 1 D and 2 D NMR), besides, their absolute and relative configurations were established by using Single-crystal X-ray diffraction analysis and CD spectrum. The anti-inflammatory potential of all compounds was evaluated by applying LPS induced RAW 264.7 macrophage inflammatory model, and the results were that none of these compounds showed activity (IC50 > 100 µM).

5.
Angew Chem Int Ed Engl ; 60(25): 13913-13917, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33829638

RESUMO

Here we report that the chemoselective activation of Tsuji's 2-(cyanomethyl)allyl carbonates to generate the palladium-trimethylenemethane 1,3-dipoles via a deprotonation strategy can be realized in the presence of Morita-Baylis-Hillman carbonates from substantial activated ketones. The following SN 2'-addition enables the formation of new 1,3-dipole species having an activated alkene moiety through a second deprotonation process, which then undergo cascade [1+2]/[3+2] annulations to furnish complex bicyclic [3.1.0]hexane frameworks having three contiguous quaternary stereogenic centers with good to excellent enantioselectivity. Moreover, by using benzoyl aldehyde-derived substrates, a [1+4]/[3+2] annulation sequence is similarly developed to produce fused cyclopenta[b]furan architectures.

6.
Org Lett ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33326232

RESUMO

The cinnamates having an ortho-formyl group can potentially form vinylogous iminium ion species under the catalysis of chiral amines, which facilitates the Diels-Alder cycloaddition reaction with the concurrently generated trienamines between dienals and amine catalysts in a regioselectivity umpolung manner. A cascade intramolecular aldol reaction was followed, finally furnishing polyhydrophenanthrene frameworks with excellent diastereo- and enantioselectivity.

7.
Org Lett ; 22(22): 8973-8977, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33175549

RESUMO

The benzylic C-H group of α,α-dicyanoolefins from 3-substituted 1-indanones could be significantly activated via transmission along the aromatic system, thus enabling dynamic kinetic resolution via a traditional reversible deprotonation-protonation process. Enantioenriched 9-substituted 9H-fluorene frameworks were finally constructed through an asymmetric vinylogous Michael addition to nitroolefins, followed by a cascade cyclization and oxidative aromatization process, under the catalysis of a chiral bifunctional thiourea-tertiary amine.

8.
Angew Chem Int Ed Engl ; 59(18): 7083-7088, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32073203

RESUMO

The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchable introduction of another stereogenic element, that is, Z/E configuration involving a polysubstituted alkene group, into the optically active stereoisomers, has not been recognized yet. Disclosed here is the pseudo-stereodivergent synthesis of highly enantioenriched tetrasubstituted alkene architectures from isatin-based Morita-Baylis-Hillman carbonates and allylic derivatives, under the cooperative catalysis of a tertiary amine and a chiral iridium complex. The success of the switchable construction of the tetrasubstituted alkene motif relies on the diastereodivergent 1,3-oxo-allylation reaction between N-allylic ylides and chiral π-allyliridium complex intermediates by ligand and substrate control, followed by the stereoselective concerted 3,3-Cope rearrangement process.

9.
Chem Rec ; 20(6): 541-555, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31609533

RESUMO

The development of synthetic protocols to access architectures with broad structural and functional diversity from readily available starting materials is very attractive in both organic and medicinal chemistry fields. Toward this objective, the multifunctional isatin-derived Morita-Baylis-Hillman (MBH) adducts provide opportunities to construct a variety of complex scaffolds containing a "privileged" oxindole motif through several catalytic pathways. By forming the ammonium or phosphonium salts with Lewis bases, isatin-derived MBH adducts can undergo allylic substitutions with a range of nucleophiles, usually in a SN 2'-SN 2' pattern. Besides, assisted by Brønsted bases, the corresponding onium salts can be converted into the allylic ylide intermediates, which can undergo various annulation reactions or even 1,3-difunctionalizations. Moreover, recent cooperative catalysis of Lewis bases and transition metal complexes further puts forward the application of isatin-derived MBH adducts. This tutorial review covers the significant transformations of isatin-derived MBH adducts, mostly in an asymmetric version, catalyzed by various Lewis bases over the past decade.

10.
Angew Chem Int Ed Engl ; 58(42): 15021-15025, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414550

RESUMO

Asymmetric reactions merging organocatalysis and metal catalysis significantly broaden the scope of organic synthesis. Nevertheless, the accomplishment of stereoselective annulations combining two types of dipole species, independently generated from the activations of organocatalysts and metal complexes, still remains as a challenging task. Now, Morita-Baylis-Hillman carbonates from isatins and carbamate-functionalized allyl carbonates could be chemoselectively activated by achiral Lewis basic tertiary amines and chiral iridium complexes. The zwitterionic allylic ylides and 1,4-π-allyliridium dipoles formed in situ are assembled in a highly stereoselective [4+3] annulation pattern. Similar cooperative catalytic strategy could be applied for the reactions of Morita-Baylis-Hillman carbonates and vinyl aziridines, furnishing an asymmetric [3+3] annulation reaction also with excellent stereocontrol.

11.
Angew Chem Int Ed Engl ; 58(12): 4036-4040, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30697888

RESUMO

Auto-tandem catalysis (ATC), in which a single catalyst promotes two or more mechanistically different reactions in a cascade pattern, provides a powerful strategy to prepare complex products from simple starting materials. Reported here is an unprecedented auto-tandem cooperative catalysis (ATCC) for Morita-Baylis-Hillman carbonates from isatins and allylic carbonates using a simple Pd(PPh3 )4 precursor. Dissociated phosphine generates phosphorus ylides and the Pd leads to π-allylpalladium complexes, and they undergo a γ-regioselective allylic-allylic alkylation reaction. Importantly, a cascade intramolecular Heck-type coupling proceeds to finally furnish spirooxindoles incorporating a 4-methylene-2-cyclopentene motif. Experimental results indicate that both Pd and phosphine play crucial roles in the catalytic Heck reaction. In addition, the asymmetric versions with either a chiral phosphine or chiral auxiliary are explored, and moderate results are obtained.

12.
Org Lett ; 20(19): 6279-6283, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30256122

RESUMO

The in-situ-generated zwitterionic allylic ylides between Morita-Baylis-Hillman carbonates from isatins and chiral tertiary amine catalysts underwent highly regioselective and enantioselective 1,3-oxo-ethynylation or 1,3-amino-sulfenylation reactions with silyl ethynyl-1,2-benziodoxol-3( 1H)-ones or N-(aryl or alkylthio)imides, respectively, giving densely functionalized products bearing a quaternary stereogenic center. An array of diversely structured scaffolds were efficiently constructed from the products, showing the synthetic versatility of the current catalytic strategy.

13.
Curr Med Sci ; 38(1): 35-42, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30074149

RESUMO

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents, such as vitamin D compounds, is a potential regimen to treat acute myeloid leukemia (AML) patients who are unfit for high-intensity chemotherapy. The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3 (1,25-D3). Here, firstly, cBioPortal database was used and we found out that vitamin D receptor (VDR) was highly expressed in acute monocytic leukemia (M5) and high VDR expression was associated with a poor survival of AML patients. Then, we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines (U937, MOLM-13, THP-1) and blasts from M5 patients than in non-monocytic cell lines (KGla and K562) and blasts from M2 patient. Finally, it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate, growth inhibition and G0/G1 arrest, while mild changes were found in the apoptosis in acute monocytic leukemia cell lines. Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia, especially for elderly and frail ones.


Assuntos
24,25-Di-Hidroxivitamina D 3/farmacologia , Antineoplásicos/farmacologia , Citarabina/farmacologia , Leucemia Monocítica Aguda/tratamento farmacológico , Vitaminas/farmacologia , 24,25-Di-Hidroxivitamina D 3/administração & dosagem , 24,25-Di-Hidroxivitamina D 3/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Sinergismo Farmacológico , Humanos , Vitaminas/administração & dosagem , Vitaminas/uso terapêutico
14.
Acta Pharmacol Sin ; 38(11): 1475-1485, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28836580

RESUMO

The intercellular communication between leukemia cells and bone marrow mesenchymal stem cells (BM-MSCs) plays more important role in chronic myeloid leukemia (CML) than we previously understood. Recently, we found that microvesicles released from human leukemia cell line K562 (K562-MVs) containing BCR-ABL1 mRNA malignantly transformed normal hematopoietic transplants. Here, we investigated whether K562-MVs contribute to the transformation of human bone marrow mesenchymal stem cells (BM-MSCs). We showed that K562-MVs could be integrated into co-cultured normal BM-MSCs and dose-dependently enhanced the proliferation of BM-MSCs. Meanwhile, K562-MVs (400 ng/mL) significantly increased the expression of BCR-ABL1 in these BM-MSCs, accompanied by the enhanced secretion of TGF-ß1. These BM-MSCs in turn could trigger the TGF-ß1-dependent proliferation of K562 cells. Moreover, we confirmed the presence of BCR-ABL1 in circulating MVs from 11 CML patients. Compared to the normal BM-MSCs, the BM-MSCs from CML patients more effectively increased the BCR-ABL1 expression and TGF-ß1 secretion in K562 cells as well as the proliferation of K562 cells. Our findings enrich the mechanisms involved in the interaction between leukemia cells and BM-MSCs and provide novel ways to monitor minimal residual disease and worthwhile approaches to treat CML.


Assuntos
Células da Medula Óssea/metabolismo , Comunicação Celular , Transformação Celular Neoplásica/genética , Micropartículas Derivadas de Células/genética , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Células-Tronco Mesenquimais/metabolismo , Adolescente , Adulto , Células da Medula Óssea/patologia , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Micropartículas Derivadas de Células/patologia , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Técnicas de Cocultura , Feminino , Proteínas de Fusão bcr-abl/sangue , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , RNA Mensageiro/sangue , RNA Mensageiro/genética , Fatores de Tempo , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral , Adulto Jovem
15.
J Huazhong Univ Sci Technolog Med Sci ; 37(2): 179-184, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28397044

RESUMO

Increasing studies have demonstrated that interferon gamma (IFN-γ), which serves as a critical inflammatory cytokine, is essential to induce the immunosuppressive effects of mesenchymal stem cells (MSCs). However, the mechanisms underlying the enhanced immunosuppressive effects of IFN-γ-stimulated MSCs (γMSCs) are not fully understood. MSC-derived microvesicles (MSC-MVs) have been viewed as potential pivotal mediators of the immunosuppressive effects of MSCs. Moreover, microRNAs (miRNAs) are important regulators of immunological processes and can be shuttled from cell to cell by MVs. The aim of our study was to analyze the the miRNA expression signature of MVs derived from γMSCs (γMSC-MVs), which may provide better understanding of the immunosuppressive property of their parent cells. Through miRNA microarray and bioinformatics analysis, we found 62 significantly differentially expressed miRNAs (DEMs) in γMSC-MVs compared with MSC-MVs. And the potential target genes and signaling pathways regulated by DEMs were predicted and analyzed. Interestingly, many DEMs and predicted signaling pathways had been demonstrated to be involved in immunoregulation. Furthermore, the network between immunoregulation-related pathways and relevant DEMs was constructed. Collectively, our research on the miRNA repertoires of γMSC-MVs not only provides new perspectives into the mechanisms underlying the enhanced immunosuppressive property of γMSCs, but also paves the way to clinical application of these potent organelles in the future.


Assuntos
Micropartículas Derivadas de Células/genética , Interferon gama/farmacologia , Células-Tronco Mesenquimais/imunologia , MicroRNAs/genética , Micropartículas Derivadas de Células/efeitos dos fármacos , Células Cultivadas , Biologia Computacional/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais
16.
J Huazhong Univ Sci Technolog Med Sci ; 35(3): 343-349, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26072071

RESUMO

This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.


Assuntos
Mieloma Múltiplo/metabolismo , NF-kappa B/antagonistas & inibidores , Sesquiterpenos/farmacologia , Fator 6 Associado a Receptor de TNF/metabolismo , Apoptose , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Mieloma Múltiplo/tratamento farmacológico , NF-kappa B/sangue , Fator de Transcrição RelA/metabolismo , Ubiquitinação/efeitos dos fármacos
17.
J Huazhong Univ Sci Technolog Med Sci ; 34(2): 176-180, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24710928

RESUMO

The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.


Assuntos
Citocinas/sangue , Leucemia Mieloide Aguda/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Citocinas/biossíntese , Diagnóstico Diferencial , Regulação Leucêmica da Expressão Gênica , Humanos , Análise em Microsséries , Prognóstico , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(2): 496-502, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24763030

RESUMO

This study was aimed to investigate a more convenient and efficient method to cultivate the human bone marrow mesenchymal stem cells by means of natural erythrocyte sedimentation principle, based on the whole bone marrow adherent method. The bone marrow was cultured with a six-well plate instead of the flasks.Firstly, the bone marrow specimen was cultivated with the MSC complete medium for 48 h, then the upper RBC-free supernatant layer was drawn and placed into the new wells to isolate MSC. Inverted microscope was used to observe the cell morphology and to record the adherent time of first cell passage, first passaging time. The traditional whole bone marrow adherent method was used as the control. The cell cycle and cell surface markers were detected by flow cytometry,and the differentiative capacity of MSC into osteocyte and adipocyte was identified by alkaline phosphatase kit and oil red O, respectively. Besides, the proliferative curve of P1,P3,P5 of BMSC was depicted by counting method. The results showed that MSC cultured by the modified method highly expressed CD90, CD105, CD13, CD44 and lowly expressed CD14, CD45, CD34. Concerning the cell cycle feature, it was found that most of the cells were in G0/G1 phase (88.76%) , followed by G2/M phase (3.04%) and S phase (8.2%), which was in accordance with stem cell cycle characteristics. The proliferative curve showed a typical "S" type, and both the oil red O and alkaline phosphatase staining of MSC were positive. Compared with the traditional method, the modified method had the advantage of high adherence rate (P = 0.0001) and shorter passaging time for the first passage (P = 0.001), with the statistically significant difference. It is concluded that there is a large number of adherent, active and suspended MSC in the RBC-free supernatant layer after the culture of bone marrow for 48 h. Isolating MSC by the modified method is more convenient and efficient than the traditional whole bone marrow adherent method.


Assuntos
Células da Medula Óssea/citologia , Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/citologia , Separação Celular , Células Cultivadas , Humanos
19.
Acta Pharmacol Sin ; 35(3): 381-93, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24374813

RESUMO

AIM: To investigate the effects of serum deprivation (SD) on microvesicles (MVs) secreted from human myeloma cells and the implications for disease progression. METHODS: RPMI 8226, U266, and KM3 human myeloma cells were incubated in medium containing 10% (non-SD) or 1% fetal bovine serum (SD) and MVs were isolated. The levels and size distribution of MVs were analyzed with flow cytometry. The protein profiles of MVs were studied using 2D SDS-PAGE, MALDI-TOF-MS, and Western blotting. NF-κB activation was analyzed using EMSA. Angiogenesis was examined in Eahy926 endothelial cells. RESULTS: Exposure of RPMI 8226 cells to SD for 24 h did not alter the number of apoptotic cells. However, SD increased the number of MVs from RPMI 8226, U266, and KM3 cells to 2.5-, 4.3-, and 3.8-fold, respectively. The size distribution of SD MVs was also significantly different from that of non-SD MVs. Three proteins ZNF224, SARM, and COBL in SD MVs were found to be up-regulated, which were involved in cell cycle regulation, signal transduction and metabolism, respectively. Co-culture of SD MVs and RPMI 8226 cells increased NF-κB activation in the target RPMI 8226 cells. Furthermore, SD MVs from RPMI 8226 cells significantly increased the microtubule formation capacity of Eahy926 endothelial cells compared with non-SD MVs. CONCLUSION: SD elevates the levels of microvesicles with different size distribution and selectively enriched proteins in human myeloma cells in vitro. The selectively enriched proteins, especially ZNF224, may play key roles in regulation of myeloma cells, allowing better adaptation to SD.


Assuntos
Comunicação Autócrina , Micropartículas Derivadas de Células/metabolismo , Meios de Cultura Livres de Soro/metabolismo , Mieloma Múltiplo/metabolismo , Proteínas do Mieloma/metabolismo , Comunicação Parácrina , Apoptose , Western Blotting , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Micropartículas Derivadas de Células/patologia , Técnicas de Cocultura , Eletroforese em Gel Bidimensional , Células Endoteliais/metabolismo , Citometria de Fluxo , Humanos , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , NF-kappa B/metabolismo , Neovascularização Fisiológica , Proteômica/métodos , Proteínas Repressoras/metabolismo , Transdução de Sinais , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fatores de Tempo
20.
Acta Pharmacol Sin ; 35(2): 230-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24374814

RESUMO

AIM: To investigate whether human multiple myeloma (MM) cells secrete microvesicles (MVs) and whether the MVs secreted from MM cells (MM-MVs) promote angiogenesis. METHODS: RPMI8226 human MM cells and EA.hy926 human umbilical vein cells were used. MVs isolated from RPMI8226 cells were characterized under laser confocal microscopy, electron microscopy and with flow cytometry. The fusion of MM-MVs and EA.hy926 cells was studied under confocal microscopy, and the transfer of CD138 to EA.hy926 cells was demonstrated with flow cytometry. The proliferation, invasion and tube formation of EA.hy926 cells in vitro were evaluated using MTT, transwell migration and tube formation assays, respectively. The vasculization of EA.hy926 cells in vivo was studied using Matrigel plug assay. The expression of IL-6 and VEGF was analyzed with PCR and ELISA. RESULTS: MM-MVs from the RPMI 8226 cells had the characteristic cup-shape with diameter of 100-1000 nm. Most of the MM-MVs expressed phosphatidylserine and the myeloma cell marker CD138, confirming that they were derived from myeloma cells. After added to EA.hy926 cells, the MM-MVs transferred CD138 to the endothelial cells and significantly stimulated the endothelial cells to proliferate, invade, secrete IL-6 and VEGF, two key angiogenic factors of myeloma, and form tubes in vitro and in vivo. CONCLUSION: Our results confirm the presence of MVs in MM cells and support the idea that MM-MVs are newfound mediators for myeloma angiogenesis and may serve as a therapeutic target to treat MM.


Assuntos
Mieloma Múltiplo/patologia , Neovascularização Patológica/patologia , Vesículas Secretórias/patologia , Linhagem Celular Tumoral , Humanos , Veias Umbilicais/patologia
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