Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biochem Biophys Res Commun ; 519(1): 1-7, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31500806

RESUMO

Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a member of the rhodopsin-like 7-transmembrane domain receptor superfamily and has high homology to LGR4 and LGR5. LGR6 is highly expressed in osteoblastic progenitors, and LGR6-deficient mice show nail and bone regeneration defect. However, the effect of LGR6 on the osteogenic differentiation of osteoblastic progenitors and its underlying mechanisms are largely unknown. In this study, we overexpressed and knockdown LGR6 with lentivirus in the preosteoblastic cell MC3T3-E1 to observe the effect of LGR6 on osteogenic differentiation and explore its possible molecular mechanism. LGR6 overexpression promoted osteogenic differentiation and mineralization by stabilizing ß-catenin to potentiate the Wnt/ß-catenin signaling pathway in MC3T3-E1 cells. Conversely, LGR6 knockdown inhibited osteogenic differentiation and mineralization by enhancing ß-catenin degradation to inactivate the Wnt/ß-catenin signaling pathway. These results reveal that LGR6 is highly expressed in osteoblastic progenitors, and promotes osteogenesis by enhancing ß-catenin stability to strengthen the Wnt signaling pathway. This study provides an important reference into the exact mechanisms of osteogenic differentiation.

2.
Biochem Biophys Res Commun ; 518(2): 212-218, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31434610

RESUMO

Aplastic anemia (AA) is a serious blood system disease that threatens human health. At present, the main cause of this disease is believed to be immune hyperfunction. However, the specific metabolic mode involved in the occurrence of lymphocytes in AA is still unknown. In addition, whether rapamycin, a specific blocker of the mTOR signaling pathway, plays a therapeutic role by inhibiting lymphocyte metabolism remains unclear. We induced an AA mouse model through the classical immune-mediated pathway and simultaneously administered rapamycin intervention therapy. First, the AA-associated phenotypic changes and the efficacy of rapamycin in the treatment of AA were discussed. Second, the proliferation and metabolic pathway of bone marrow (BM) lymphocytes in AA and the effect of rapamycin on this process were determined. Finally, the expression levels of mTOR pathway-related proteins were analyzed. By inhibiting the mTOR signaling pathway, rapamycin could ameliorate the phenotype of the immune-mediated AA model and inhibit the proliferation of T cells by preventing cell cycle transition from G0 to G1 phase. Moreover, we found that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and that rapamycin can inhibit this process. We confirmed that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and further extended the mechanism of rapamycin in treating AA by inhibiting the mTOR signaling pathway. This viewpoint may provide a new therapeutic idea for clinical applications.

3.
Leukemia ; 33(10): 2365-2378, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30940905

RESUMO

Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.g., Ara-C, DNR, 6-MP) induced the expression of niche-protecting cytokines (GDF15, CCL3 and CCL4) in both ALL cell lines and primary cells in vitro. The ATM and NF-κB pathways were activated after chemotherapy treatment, and the pharmacological or genetic inhibition of these pathways significantly reversed the cytokine upregulation. Besides, chemotherapy-induced NF-κB activation was dependent on ATM-TRAF6 signaling, and NF-κB transcription factor p65 directly regulated the cytokines expression. Furthermore, we found that both pharmacological and genetic perturbation of ATM and p65 significantly decreased the residual ALL cells after Ara-C treatment in ALL xenograft mouse models. Together, these results demonstrated that ATM-dependent NF-κB activation mediated the cytokines induction by chemotherapy and ALL resistance to chemotherapeutics. Inhibition of ATM-dependent NF-κB pathway can sensitize ALL to chemotherapeutics, providing a new strategy to eradicate residual chemo-resistant ALL cells.

4.
PeerJ ; 7: e6619, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881770

RESUMO

We used qingbo (Spinibarbus sinensis) and Chinese crucian carp (Carassius auratus) to test whether numerical discrimination could be improved by the coexistence and possible cooperation of conspecies or heterospecies. We conducted a spontaneous shoal choice test of singletons, conspecific dyads and heterospecific dyads under different numerical comparisons (8 vs. 12, 9 vs. 12 and 10 vs. 12). Singletons of qingbo could discriminate only 8 vs. 12, whereas the dyads of qingbo showed better numerical acuity, as they could discriminate 10 vs. 12. Crucian carp may have poor numerical ability, as both singleton and dyads showed no significant preference for larger stimulus shoals, even at the 'easier' numerical discrimination, that is, 8 vs. 12. Furthermore, heterospecific dyads of crucian carp and qingbo did not show significant preference for larger shoals at any numerical comparison in the present study. It is suggested that both the numerical ability and the possibility for improvement by interindividual interaction and hence cooperation might vary among fish species, and the interaction between heterospecies in the present study showed negative effect on numerical ability possibly due to the different behavioural and cognitive traits which make the information transfer and consensus difficult to reach.

5.
Anim Cogn ; 22(2): 133-143, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30542940

RESUMO

Group living confers ecological benefits, and the associated fitness gain may be positively related to the size of the group. Thus, the ability to discriminate numerical differences may confer important fitness advantages in social fish. There is evidence that this ability can be improved by behavioral interactions among individuals of the same species. Here, we looked for this effect in both conspecific and heterospecific dyads. In Chinese bream and grass carp, we measured the sociability and shoal preferences of singletons, conspecific dyads and heterospecific dyads presented with different numerical comparisons (0 vs 8, 2 vs 8, 4 vs 8, 6 vs 8 and 8 vs 8). Chinese bream generally showed higher sociability than did grass carp, but grass carp in heterospecific dyads showed improved sociability that was similar to that of Chinese bream. Among the comparisons, both grass carp and Chinese bream singletons could only discriminate the comparison of 2 vs 8, suggesting lower quantitative abilities in these fish species compared to other fish species. Grass carp dyads were more successful in discriminating between 6 and 8 than were singletons, although no such improvement was observed in their discrimination between 4 and 8. In contrast, numerical ability did not vary between singletons and conspecific dyads in Chinese bream. More interestingly, Chinese bream and grass carp in heterospecific groups could discriminate between 4 and 8, but neither species showed a preference when presented with 6 and 8. Our results suggested that interaction between conspecific grass carp might improve their joint numerical ability, and a similar process might occur in Chinese bream in heterospecific dyads. However, the mechanism underlying the differences in improvements in numerical ability requires further investigation. The improved cognitive ability of heterospecific dyads might yield important fitness advantages for predator avoidance and efficient foraging in the wild.


Assuntos
Cognição , Peixes , Comportamento Social , Animais
6.
Molecules ; 23(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127238

RESUMO

Acanthopanax senticosus (Rupr. Maxim.) Harms (ASH) and Acanthopanax sessiliflorus (Rupr. Maxim.) Seem (ASS), are members of the Araliaceae family, and both are used in Asian countries. These herbals have drawn much attention in recent years due to their strong biological activity, with innocuity and little side effects. However, the common and distinct mode of compound profiles between ASH and ASS is still unclear. In this study, a high performance liquid chromatograph-mass spectrometry (HPLC-MS) method was developed to simultaneously quantify the seven major active compounds, including protocatechuate, eleutheroside B, eleutheroside E, isofraxidin, hyperoside, kaempferol and oleanolic acid. Then the targeted metabolomics were conducted to identify 19 phenolic compounds, with tight relation to the above mentioned active compounds, including nine C6C3C6-type, six C6C3-type and four C6C1-type in the two Acanthopanax species studied here. The results showed that the seven active compounds presented a similar trend of changes in different tissues, with more abundant accumulation in roots and stems for both plants. From the view of plant species, the ASH plants possess higher abundance of compounds, especially in the tissues of roots and stems. For phenolics, the 19 phenols detected here could be clearly grouped into five main clusters based on their tissue-specific accumulation patterns. Roots are the tissue for the most abundance of their accumulations. C6C3C6-type compounds are the most widely existing type in both plants. In conclusion, the tissue- and species-specificity in accumulation of seven active compounds and phenolics were revealed in two Acanthopanax species.


Assuntos
Araliaceae/química , Hidroxibenzoatos/metabolismo , Metabolômica/métodos , Extratos Vegetais/análise , Benzopiranos/análise , Cromatografia Líquida de Alta Pressão , Hidroxibenzoatos/análise , Ácido Oleanólico/análise , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Especificidade da Espécie , Espectrometria de Massas em Tandem
7.
J Exp Clin Cancer Res ; 37(1): 204, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157922

RESUMO

BACKGROUND: Considerable efforts have been devoted toward the uncovering of the molecular mechanisms underlying the maintenance of hematopoietic stem cells (HSCs) by the normal bone marrow (BM) niche. Previously, we demonstrated that a chemotherapy-induced niche, which is mainly composed of mesenchymal stem cells (MSCs), protects the residual B-cell acute lymphoblastic leukemia (B-ALL) cells from the insult of chemotherapeutic drugs. However, the roles of chemotherapy-induced niche on HSCs functions in B-ALL remain unclear. METHODS: We established an oncogenic N-MYC-driven B-ALL mouse model, which were subsequently treated with common chemotherapy drug cytarabine (Ara-C) and daunorubicin (DNR). After treatment, the structures of the BM niche were imaged by immunofluorescence staining. Then, the self-renewal and differentiation capability of the MSCs in the BM after Ara-C and DNR treatment were studied by ex vivo culture and gene expression analysis with RNA-seq and qRT-PCR. The effects of chemotherapy-induced niche on the hematopoietic reconstitution of HSCs were determined with series transplantation assay. Furthermore, the cell cycle, ROS level, mitochondrial membrane potential and cell apoptosis of HSCs were detected by flow cytometry. RESULTS: The MSCs, which is the main component of chemotherapy-induced BM niche, have decreased self-renewal capability and are prone to differentiate into adipocytes and chondrocytes. The results of gene expression analysis with RNA-seq showed that the MSCs have reduced levels of cytokines, including SCF, CXCL12, ANGPT1, VCAM1, and IL7. Furthermore, the chemotherapy-induced niche perturbed the hematopoietic reconstitution of HSCs in our N-MYC-driven B-ALL mouse model by promoting HSCs to enter cell cycle and increasing intracellular ROS levels and mitochondrial membrane potential of HSCs, which lead to the cell apoptosis of HSCs. CONCLUSIONS: Chemotherapy-induced BM niche perturbs the hematopoietic reconstitution of HSCs by increasing intracellular ROS level and inducing cell apoptosis.


Assuntos
Citarabina/administração & dosagem , Células-Tronco Hematopoéticas/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Autorrenovação Celular/genética , Modelos Animais de Doenças , Citometria de Fluxo , Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/patologia , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Espécies Reativas de Oxigênio/metabolismo , Nicho de Células-Tronco/genética
8.
BMC Genomics ; 19(1): 508, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29966514

RESUMO

BACKGROUND: The medicinal plant, Catharanthus roseus (C. roseus), accumulates a wide range of terpenoid indole alkaloids (TIAs). Ethylene (ET) and methyl-jasmonate (MeJA) were previously reported as effective elicitors for the production of various valuable secondary metabolites of C. roseus, while a few ET or MeJA induced transcriptomic research is yet reported on this species. In this study, the de-novo transcriptome assembly of C. roseus is performed by using the next-generation sequencing technology. RESULTS: The result shows that phenolic biosynthesis genes respond specifically to ET in leaves, monoterpenoid biosynthesis genes respond specifically to MeJA in roots. By screening the database, 23 ATP-binding cassette (ABC) transporter partial sequences are identified in C. roseus. On this basis, more than 80 key genes that encode key enzymes (namely TIA pathway, transcriptional factor (TF) and candidate ABC transporter) of alkaloid synthesis in TIA biosynthetic pathways are chosen to explore the integrative responses to ET and MeJA at the transcriptional level. Our data indicated that TIA accumulation is strictly regulated by the TF ethylene responsive factor (ERF) and bHLH iridoid synthesis 1 (BIS1). The heatmap, combined with principal component analysis (PCA) of C. roseus, shows that ERF co-expression with ABC2 and ABC8 specific expression in roots affect the root-specific accumulation of vinblastine in C. roseus. On the contrast, BIS1 activities follow a similar pattern of ABC3 and CrTPT2 specific expression in leaves, which affects the leaf-specific accumulation of vindoline in C. roseus. CONCLUSIONS: Results presented above illustrate that ethylene has a stronger effect than MeJA on TIA induction at both transcriptional and metabolite level. Furthermore, meta-analysis reveals that ERF and BIS1 form a positive feedback loop connecting two ABC transporters respectively and are actively involved in TIAs responding to ET and MeJA in C. roseus.


Assuntos
Acetatos/farmacologia , Catharanthus/genética , Ciclopentanos/farmacologia , Etilenos/farmacologia , Oxilipinas/farmacologia , Alcaloides de Triptamina e Secologanina/metabolismo , Transcriptoma/efeitos dos fármacos , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Catharanthus/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Análise de Componente Principal , Alcaloides de Triptamina e Secologanina/química
9.
Artigo em Inglês | MEDLINE | ID: mdl-29649754

RESUMO

Astragalus is one of the most popular Chinese herbal. Control of Astragalus quantity is most important, since that various varieties and ages largely affect bioactive metabolites and different pharmacological effects. Astragalus mongholicus and Astragalus membranaceus are both major sources of Astragalus according to the provisions in the Chinese Pharmacopoeia. Thus, a sensitive and rapid UPLC-MS/MS method for the simultaneous determination of l-Phenylalanine, Isoliquiritigenin, Liquiritigenin, Daidzein, Formononetin, Ononin, Calycosin, Calycosin-7-glucoside, Cycloastragenol, Astragaloside I, Astragaloside II, Astragaloside III and Astragaloside IV was established in this study. The detection was accomplished by MRM scanning in the positive ionization mode. Calibration curves offered linear ranges with r2 > 0.999. The method was successfully validated for the linearity, intra-day and inter day precisions, accuracy, recovery, matrix effect and stability. Then this method was successfully applied to detect the contents of 13 target flavonoids and triterpenoids metabolites in different organs and ages of A. mongholicus and A. membranaceus. Significant organs-, ages- and varieties- specificity of the 13 target metabolites were observed and discussed. The results provided basis and support for further exploration of the distribution of bioactive metabolites, namely flavonoids and triterpenoids, in different organs and ages of two Astragalus varieties. This method should be applicable to various Astragalus matrices for the quantitative analysis of the target flavonoids and triterpenoids.


Assuntos
Astragalus propinquus/química , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Espectrometria de Massas em Tandem/métodos , Triterpenos/análise , Flavonoides/química , Modelos Lineares , Extratos Vegetais/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Triterpenos/química
10.
J Nat Prod ; 81(2): 335-342, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29406718

RESUMO

The medicinal plant Catharanthus roseus accumulates large numbers of terpenoid indole alkaloids (TIAs), including the pharmaceutically important vinblastine, vincristine, ajmalicine, and serpentine. The phytohormone ethylene or methyl jasmonate (MeJA) can markedly enhance alkaloid accumulation. The interaction between ethylene or MeJA in the regulation of TIA biosynthesis in C. roseus is unknown. Here, a metabolomics platform is reported that is based on liquid chromatography (LC) coupled with time-of-flight mass spectrometry to study candidate components for TIA biosynthesis, which is controlled by ethylene or MeJA in C. roseus. Multivariate analysis identified 16 potential metabolites mostly associated with TIA metabolic pathways and seven targeted metabolites, outlining the TIA biosynthesis metabolic networks controlled by ethylene or MeJA. Interestingly, ethylene and MeJA regulate the 2-C-methyl-d-erythritol 4-phosphate (MEP) and acetate-mevalonate (MVA) pathways through AACT and HMGS and through DXS, respectively, to induce TIA biosynthesis in C. roseus. Overall, both nontargeted and targeted metabolomics, as well as transcript analysis, were used to reveal that MeJA and ethylene control different metabolic networks to induce TIA biosynthesis.


Assuntos
Acetatos/metabolismo , Catharanthus/metabolismo , Ciclopentanos/metabolismo , Etilenos/metabolismo , Redes e Vias Metabólicas/fisiologia , Oxilipinas/metabolismo , Alcaloides de Triptamina e Secologanina/metabolismo , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Ácido Mevalônico/metabolismo , Vimblastina/metabolismo , Vincristina/metabolismo
11.
Photochem Photobiol ; 94(1): 115-125, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881500

RESUMO

In this work, the changes in isoflavone levels and the expression of genes involved in their biosynthesis were studied in two Astragalus by UPLC-MS and real-time PCR after 10 days of UV-B treatment (λmax  = 313 nm, 804 J m-2 ). Isoflavones were significantly induced by UV-B irradiation. The influence might be activated by the regulation of these target genes. Our results indicate that (1) the resistance of Astragalus membranaceus might not be as good as Astragalus mongholicus in the enhanced UV-B radiation environment; (2) the enhanced accumulation of calycosin and calycosin-7-glucoside with UV-B treatment in roots of A. mongholicus might be derived from formononetin which is synthesized in the leaves; (3) the glycosylation process could be stimulated and activated by the enhanced UV-B radiation in both A. mongholicus and A. membranaceus. In other words, glycosylation of isoflavones might play a crucial role for two Astragalus plants in response to UV-B stress. Overall, this study offered a feasible elicitation strategy to understand the accumulation pattern of isoflavone in A. mongholicus and A. membranaceus, and also provided a reference for the changes in isoflavone levels of Astragalus in UV-B enhanced environment in the future.


Assuntos
Astrágalo (Planta)/efeitos da radiação , Glucosídeos/metabolismo , Isoflavonas/metabolismo , Tolerância a Radiação/genética , Estresse Fisiológico/genética , Análise de Variância , Astrágalo (Planta)/genética , Astrágalo (Planta)/fisiologia , Genes de Plantas/genética , Glucosídeos/genética , Glicosilação , Isoflavonas/genética , Estrutura Molecular , Folhas de Planta/genética , Folhas de Planta/fisiologia , Folhas de Planta/efeitos da radiação , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Raízes de Plantas/efeitos da radiação , RNA de Plantas/genética , Raios Ultravioleta
12.
PeerJ ; 5: e3397, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28584722

RESUMO

Mixed-species shoals of fish are frequently found in the field; however, little is known about individual-level interactions within these groups. We examined the collective motion of two cyprinid species (Chinese bream, Parabramis pekinensis, and qingbo, Spinibarbus sinensis) that occupy partially overlapping habitats but differ in social behavior (high vs low aggressiveness) and preferred flow regime (slow vs fast water velocity). We extracted measures of collective motion from video recordings of eight replicate groups of four individuals of either Chinese bream or qingbo (conspecific group) or two Chinese bream plus two qingbo (heterospecific group). Chinese bream in conspecific groups showed lower percent time moving and mean swimming speed but a similar speed while moving as compared to the qingbo conspecific groups. However, the difference in mean swimming speed and percent time moving vanished in the heterospecific group as Chinese bream elevated their swimming activity to coordinate with qingbo. This finding suggests that the two species may share similar interaction rules regarding shoaling behavior. The conspecific groups of qingbo exhibited a greater distance between group members than Chinese bream, suggesting a difference in cohesion. However, the inter-individual distances of all fish were similar in the heterospecific group. Qingbo in the heterospecific group swam more frequently at the front compared to Chinese bream, possibly due to their higher activity level. We also measured the startle response to an artificial stimulus and found that there was no significant difference among groups. In conclusion, the present study demonstrated that in the heterospecific groups, Chinese bream elevated their percent time moving while qingbo decreased their inter-individual distance to achieve consistent collective movement; thus, the two species showed similar behavior in the mixed-species group.

13.
PeerJ ; 5: e3222, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28439473

RESUMO

Predation is one of the key factors governing patterns in natural systems, and adjustments of prey behaviors in response to a predator stimulus can have important ecological implications for wild fish. To investigate the effects of predators on the behavior of prey fish and to test whether the possible effects varied with predator size, black carp (Mylopharyngodon piceus) and snakehead (Channa argus) (a size-matched predator treatment with a similar body size to prey fish and a larger predator treatment with approximately 2.7 times of the body mass of prey fish) were selected to function as prey and predator, respectively. Their spontaneous activities were videorecorded in a central circular arena surrounded by a ring holding the stimulus fish. The distance between prey and predator fish was approximately 200% of the distance between two prey fish, which suggested that black carp can distinguish their conspecifics from heterospecifics and probably recognize the snakehead as a potential predator. The prey fish spent substantially less time moving and exhibited an overall shorter total distance of movement after the size-matched or large predator was introduced, which possibly occurred due to increased vigilance or efforts to reduce the possibility of detection by potential predators. However, there was no significant difference in either distance or spontaneous activities between two predator treatments. These findings suggested that (1) an anti-predator strategy in black carp might involve maintaining a safe distance, decreasing activity and possibly increased vigilance and that (2) the behaviors of prey response to predators were not influenced by their relative size difference.

14.
World J Gastroenterol ; 23(10): 1780-1786, 2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28348483

RESUMO

AIM: To compare the expression levels of interleukin (IL)-6 in colorectal cancer (CRC) tissues and adjacent non-cancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of CRC. METHODS: Fifty CRC tissue specimens and 50 matched adjacent mucosa specimens were collected. The expression of IL-6 in these clinical samples was examined by immunohistochemical staining. The correlation between IL-6 expression and clinicopathological parameters was assessed by statistical analysis. RESULTS: IL-6 expression was significantly elevated in CRC tissues compared with noncancerous tissues (P < 0.001). IL-6 expression was positively correlated with tumour TNM stage (P < 0.001), but a negative correlation was detected between IL-6 expression and tumor histological differentiation in CRC (P < 0.05). Furthermore, IL-6 expression was associated with invasion depth and lymph node metastasis in CRC. CONCLUSION: IL-6 might be a useful marker for predicting a poor prognosis in patients with CRC and might be used as a potential therapeutic target in CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico
15.
Molecules ; 22(3)2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28335577

RESUMO

Ginsenosides, the major compounds present in ginseng, are known to have numerous physiological and pharmacological effects. The physiological processes, enzymes and genes involved in ginsenoside synthesis in P. ginseng have been well characterized. However, relatively little information is known about the dynamic metabolic changes that occur during ginsenoside accumulation in ginseng. To explore this topic, we isolated metabolites from different tissues at different growth stages, and identified and characterized them by using gas chromatography coupled with mass spectrometry (GC-MS). The results showed that a total of 30, 16, 20, 36 and 31 metabolites were identified and involved in different developmental stages in leaf, stem, petiole, lateral root and main root, respectively. To investigate the contribution of tissue to the biosynthesis of ginsenosides, we examined the metabolic changes of leaf, stem, petiole, lateral root and main root during five development stages: 1-, 2-, 3-, 4- and 5-years. The score plots of partial least squares-discriminate analysis (PLS-DA) showed clear discrimination between growth stages and tissue samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis in the same tissue at different growth stages indicated profound biochemical changes in several pathways, including carbohydrate metabolism and pentose phosphate metabolism, in addition, the tissues displayed significant variations in amino acid metabolism, sugar metabolism and energy metabolism. These results should facilitate further dissection of the metabolic flux regulation of ginsenoside accumulation in different developmental stages or different tissues of ginseng.


Assuntos
Ginsenosídeos/análise , Metabolômica/métodos , Panax/química , Panax/crescimento & desenvolvimento , Metabolismo dos Carboidratos , Metabolismo Energético , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ginsenosídeos/química , Análise dos Mínimos Quadrados , Via de Pentose Fosfato , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/química , Raízes de Plantas/crescimento & desenvolvimento , Caules de Planta/química , Caules de Planta/crescimento & desenvolvimento
16.
J Pharm Biomed Anal ; 135: 176-185, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28038384

RESUMO

The traditional medicine Ginseng mainly including Panax ginseng and Panax quinquefolius is the most widely consumed herbal product in the world. Despite the extensive investigation of biosynthetic pathway of the active compounds ginsenosides, our current understanding of the metabolic interlink between ginsenosides synthesis and primary metabolism at the whole-plant level. In this study, the tissue-specific profiling of primary and the secondary metabolites in two different species of ginseng were investigated by gas chromatography- and liquid chromatography coupled to mass spectrometry. A complex continuous coordination of primary- and secondary-metabolic network was modulated by tissues and species factors during growth. The results showed that altogether 149 primary compounds and 10 ginsenosides were identified from main roots, lateral roots, stems, petioles and leaves in P. ginseng and P. quinquefolius. The partial least squares-discriminate analysis (PLS-DA) revealed obvious compounds distinction among tissue-specific districts relative to species. To survey the dedication of carbon and nitrogen metabolism in different tissues to the accumulation of ginsenosides, we inspected the tissue-specific metabolic changes. Our study testified that the ginsenosides content was dependent on main roots and lateral roots energy metabolism, whereas independent of leaves and petiole photosynthesis during ginsenosides accumulation. When tow species were compared, the results indicated that high rates of C assimilation to C accumulation are closely associated with ginsenosides accumulation in P. ginseng main roots and P. quinquefolius lateral roots, respectively. Taken together, our results suggest that tissue-specific metabolites profiling dynamically changed in process of ginsenosides biosynthesis, which may offer a new train of thoughts to the mechanisms of the ginsenosides biosynthesis at the metabolite level.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Ginsenosídeos/metabolismo , Metabolômica/métodos , Panax/metabolismo , Saponinas/metabolismo , Cromatografia Líquida/métodos , Ginsenosídeos/análise , Panax/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Saponinas/análise , Especificidade da Espécie , Distribuição Tecidual/fisiologia
17.
Springerplus ; 5(1): 1770, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27795912

RESUMO

As the king of herb plants, ginseng has been used for nearly 5000 years in medicines in Asia and recently in the West. Ginsenosides, the main active constituents in Panax herbs, have prominent immunoregulatory effects. Although extensively studied in the roots, ginsenosides have not been studied with regard to their profiles and natural variations in the leaf, stem, petiole, lateral root, and main roots during development or among species. In this study, a sensitive ultra-performance liquid chromatography-electrospray ionization-mass spectrometry method with a shorter chromatographic running time was developed and validated for simultaneous quantification of ten ginsenosides. Comparing ginsenoside contents in various parts during different developmental stages revealed part-specific accumulation of most ginsenosides. Further investigation indicated that Rg3 accumulated at significantly higher levels in the petiole of P. ginseng than in that of P. quinquefolius. The relative ratio of ginsenoside Rb2 to Rb1 appears to be a candidate metabolic marker for identifying the ginseng cultivar within a diverse collection of ginseng accessions. In addition, the PCA showed that aboveground parts differed significantly between species and can be considered as species-specific markers rather than roots. This comprehensive survey, providing reliable, affordable and adequate scientific evidence, could be used to differentiate two species and discriminate ginseng cultivar ages.

18.
Springerplus ; 5(1): 927, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27386371

RESUMO

Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao (A. mongholicus, family Leguminosae) is one of the most important traditional Chinese herbs because it contains lots of bioactive metabolites, which have beneficial and pharmacological effects on health. Simultaneously, it has been proved to be a salt-tolerant plant-one of the potential species to control the soil salinization. Therefore, a sensitive and specific ultra-pressure liquid chromatography coupled with tandem mass spectrometric (UPLC-MS/MS) method was developed and validated for the simultaneous determination of six main bioactive metabolites, astragaloside IV, cycloastragenol, calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin in different organs of A. mongholicus. The detection was accomplished by multiple-reaction monitoring (MRM) scanning via electrospray ionization source operating in the positive ionization mode. Calibration curves offered linear ranges of two orders of magnitude with R(2) > 0.99. The method was fully validated for the linearity, intra-day and inter day precisions, accuracy, recovery, matrix effect and stability. Then this method was successfully applied to detect the content of major bioactive metabolites in different plant organs of A. mongholicus under salt stress. Significant variations in the content of six bioactive metabolites were observed after been processed by different levels of salinity in different part of plant. The results support for further exploration of the salt-tolerant mechanisms in A. mongholicus and its possibility as the species that control the soil salinization. Meanwhile, we established a UPLC-MS/MS assay of the trace components in seedling of A. mongholicus in this study.

19.
Front Physiol ; 7: 217, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27375495

RESUMO

Phenolic compounds belong to a class of secondary metabolites and are implicated in a wide range of responsive mechanisms in plants triggered by both biotic and abiotic elicitors. In this study, we approached the combinational effects of ethylene and MeJA (methyl jasmonate) on phenolic compounds profiles and gene expressions in the medicinal plant Catharanthus roseus. In virtue of a widely non-targeted metabolomics method, we identified a total of 34 kinds of phenolic compounds in the leaves, composed by 7 C6C1-, 11 C6C3-, and 16 C6C3C6 compounds. In addition, 7 kinds of intermediates critical for the biosynthesis of phenolic compounds and alkaloids were identified and discussed with phenolic metabolism. The combinational actions of ethylene and MeJA effectively promoted the total phenolic compounds, especially the C6C1 compounds (such as salicylic acid, benzoic acid) and C6C3 ones (such as cinnamic acid, sinapic acid). In contrast, the C6C3C6 compounds displayed a notably inhibitory trend in this case. Subsequently, the gene-to-metabolite networks were drawn up by searching for correlations between the expression profiles of 5 gene tags and the accumulation profiles of 41 metabolite peaks. Generally, we provide an insight into the controlling mode of ethylene-MeJA combination on phenolic metabolism in C. roseus leaves.

20.
Biomed Res Int ; 2016: 3708187, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27314017

RESUMO

We selected different concentrations of ethephon, to stress C. roseus. We used qRT-PCR and HPLC followed by PCA to obtain comprehensive profiling of the vinblastine biosynthesis in response to ethephon. Based on our findings, the results showed that the high concentration of ethephon had a positive effect at both transcriptional and metabolite level. Meanwhile, there was a remarkable decrease of hydrogen peroxide content and a promoted peroxidase activity in leaves. The loading plot combination with correlation analysis suggested that CrPrx1 could be regarded as a positive regulator and interacts with ethylene response factor (ERF) to play a key role in vinblastine content and peroxidase (POD) activity. This study provides the foundation for a better understanding of the regulation and accumulation of vinblastine in response to ethephon.


Assuntos
Catharanthus/genética , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas/genética , Vimblastina/metabolismo , Catharanthus/metabolismo , Etilenos/análise , Compostos Organofosforados/farmacologia , Oxirredução , Vimblastina/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA