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1.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500111

RESUMO

Purple turnip Brassica rapa ssp. rapa is highly appreciated by consumers but the metabolites and molecular mechanisms underlying the root skin pigmentation remain open to study. Herein, we analyzed the anthocyanin composition in purple turnip (PT) and green turnip (GT) at five developmental stages. A total of 21 anthocyanins were detected and classified into the six major anthocynanin aglycones. Distinctly, PT contains 20 times higher levels of anthocyanins than GT, which explain the difference in the root skin pigmentation. We further sequenced the transcriptomes and analyzed the differentially expressed genes between the two turnips. We found that PT essentially diverts dihydroflavonols to the biosynthesis of anthocyanins over flavonols biosynthesis by strongly down-regulating one flavonol synthase gene, while strikingly up-regulating dihydroflavonol 4-reductase (DFR), anthocyanidin synthase and UDP-glucose: flavonoid-3-O-glucosyltransferase genes as compared to GT. Moreover, a nonsense mutation identified in the coding sequence of the DFR gene may lead to a nonfunctional protein, adding another hurdle to the accumulation of anthocyanin in GT. We also uncovered several key members of MYB, bHLH and WRKY families as the putative main drivers of transcriptional changes between the two turnips. Overall, this study provides new tools for modifying anthocyanin content and improving turnip nutritional quality.

2.
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.

3.
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.

4.
Nat Prod Res ; : 1-4, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31282217

RESUMO

Suaeda glauca and Puccinellia tenuiflora are two important saline-alkali tolerant plants that can improve the soil properties. For exploring the different tolerance mechanisms between them, GC-MS-based metabolomics was used to comprehensively evaluate the primary metabolites differences, a total of 51 different metabolites were present in different quantities. The identified compounds were mainly 11 sugars, 7 amino acids, 5 alcohols and 18 organic acids; they play an important role in responding to the saline-alkali stress and distinguish between S. glauca and P. tenuiflora. All identified metabolites classes showed similar trend to largely accumulate in P. tenuiflora roots and S. glauca shoots, this reveals that the two plants used different physiological strategies to cope with saline-alkali stress.

5.
Environ Sci Pollut Res Int ; 26(22): 22173-22188, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148001

RESUMO

Formation dip angle and the distortion of salinity affect the spatial distribution and storage capacity of carbon dioxide (CO2). In this numerical study, based on an actual CO2 injection demonstration project (Shiqianfeng group in the Ordos Basin) in China, CO2 was injected for a period of 20 years at four different formation dip angles (0°, 5°, 10°, 15°). In conjunction, some salinity values were chosen, ranging from saturation salinity to no salinity. A three-dimensional (3D) model was established to systematically explore the influence of different formation dip angles and salinities on the CO2 spatial distribution and storage amount. The simulation results showed that larger salinity and higher pressure near the injection well will lead the CO2 gas-phase saturation and mass fraction to be smaller for a given formation dip angle. When salinity is held constant at the saturation value, a larger dip angle will cause a smaller CO2 gas saturation in the upper right units of the injection well, and a larger gas saturation in the lower left units at the 20th year of CO2 injection. For large salinity values (full, half, and quarter saturation salinity), the larger the formation dip angle is, the greater the CO2 total storage amount. For smaller salinity values (0.00 and 0.03), a transition point existed (at 8 and 18.2 years) during the 20-year injection period. Before the transition point, the CO2 total storage amount also increases with the dip angle. After the transition point, however, the larger the formation dip angle is, the smaller the CO2 total storage amount becomes. In addition, a lower salinity may lead to the earlier appearance of the transition point.


Assuntos
Dióxido de Carbono/análise , China , Pressão , Salinidade
6.
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.

7.
J Vis Exp ; (145)2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30907868

RESUMO

Cell movement is a critical property of trophoblasts during placental development and early pregnancy. The significance of proper trophoblast migration and invasion is demonstrated by pregnancy disorders such as pre-eclampsia and intrauterine growth restriction, which are associated with inadequate trophoblast invasion of the maternal vasculature. Unfortunately, our understanding of the mechanisms by which the placenta develops from migrating trophoblasts is limited. In vitro analysis of cell migration via the scratch assay is a useful tool in identifying factors that regulate trophoblast migratory capacity. However, this assay alone does not define the cellular changes that can result in altered cell migration. This protocol describes three different in vitro assays that are used collectively to evaluate trophoblast cell movement: the scratch assay, the invasion assay, and the proliferation assay. The protocols described here may also be modified for use in other cell lines to quantify cell movement in response to stimuli. These methods allow investigators to identify individual factors that contribute to the cell movement and provide a thorough examination of potential mechanisms underlying apparent changes in cell migration.


Assuntos
Bioensaio/métodos , Movimento Celular , Primeiro Trimestre da Gravidez/fisiologia , Trofoblastos/citologia , Linhagem Celular , Proliferação de Células , Feminino , Humanos , Gravidez , Trofoblastos/metabolismo
8.
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.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30862063

RESUMO

Groundwater is the most important water resource, on which depends human geo-economic development and survival. Recent environmental changes and anthropogenic activities render groundwater severely vulnerable. Groundwater in Central Sindh, Pakistan, is facing a similar situation. Hydrogeochemical characteristics of the groundwater in the said region were investigated by analyzing 59 groundwater samples via agricultural and drinking indices, using various statistical methods and graphical approaches to identify factors affecting groundwater. Major reactions occurring in the groundwater system were quantified by hydrogeochemical modeling. A statistical summary reveals the abundance of cations is Na⁺ > Ca2+ > Mg2+ > K⁺, while the abundance of anions is HCO3- > Cl- > SO4². Groundwater chemistry is mainly of rock dominance. Correlation analysis and graphical relationships between ions reveal that ion exchange and rock weathering such as the dissolution of halite, albite, and dissolution of carbonate minerals are important rock⁻water interactions, governing the evolution of groundwater chemistry. Hydrochemical facies are predominantly of mixed CaMgCl and Na-Cl type, with few samples of Ca-HCO3 type, which constitutes fresh recharged water. Based on the Water Quality Index (WQI), 28.82% samples were found to be unsuitable for drinking. A United States Salinity Laboratory (USSL) diagram, Wilcox diagram, and other agricultural indices indicate that majority of the groundwater samples fall within the acceptable range for irrigation purposes.


Assuntos
Água Subterrânea/química , Poluentes Químicos da Água/análise , Qualidade da Água/normas , Agricultura , Monitoramento Ambiental/métodos , Humanos , Paquistão
10.
Tree Physiol ; 39(3): 372-380, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289548

RESUMO

Camptothecin (CPT) has powerful biological activities and its analogs, irinothecan and topothecan, are effective anti-cancer drugs for clinical therapy. Camptothecin was first isolated from Camptotheca acuminata and its low accumulation in planta limits drug supply in the market. Previous works have confirmed that many environmental factors and plant hormones/elicitors could regulate CPT biosynthesis, but only light irradiance has a negative effect on CPT production in C. acuminata. Although light irradiance has been identified as a negative CPT biosynthesis regulator in C. acuminata for many years, the mechanisms of this regulation are still unknown. In order to search possible signal components involved in the process of light-regulated CPT biosynthesis, coexpression analysis was carried out according to the transcriptome database of Camptotheca above-ground green tissues. From coexpression analysis, a light-responsive bZIP transcription factor, CaLMF (Light-Mediated CPT biosynthesis Factor), was identified and further investigations showed that overexpression of CaLMF down-regulated the expression of CPT biosynthesis genes and decreased the accumulation of CPT in leaves, while light-regulated expression of CPT biosynthesis genes and CPT production were abolished in CaLMF silencing leaves under shading treatment. Our results show that CaLMF is a significant light signaling component, which mediates light-regulated CPT biosynthesis in C. acuminata.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Camptotheca/genética , Camptotecina/biossíntese , Proteínas de Plantas/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Camptotheca/metabolismo , Camptotecina/efeitos da radiação , Perfilação da Expressão Gênica , Luz , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Transcriptoma
11.
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
12.
Anim Cogn ; 21(6): 813-820, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30242668

RESUMO

Fish typically prefer to live in big shoals due to the associated ecological benefits. Shoaling is a behavior that depends on the ability to quantitatively discriminate. The fundamental mechanism involved in quantity discrimination determines whether fish can discriminate a shoal using numerical discrete cues (e.g., number of shoal members), non-numerical continuous traits (e.g., total body surface area) or both; however, the mechanism is currently a controversial topic. In the present study, we used a spontaneous choice experiment to test whether guppy (Poecilia reticulata), zebrafish (Danio rerio), Chinese crucian carp (Carassius auratus) and qingbo (Spinibarbus sinensis) rely on continuous (i.e., body surface area) or discrete (i.e., number of shoal members) information for shoal selection by altering the body surface area (cumulative body surface area ratio of 3:2 or 1:1) between two stimulus shoals with a different number of members (2 individuals vs 3 individuals). All four fish species preferred to shoal with the stimulus shoal with the larger cumulative surface area even if the shoal had fewer members; however, fish showed no shoal preference when the cumulative surface body areas of both stimulus shoals were equal. Furthermore, qingbo did not numerically discriminate between a shoal with 1 individual and a shoal with 3 individuals when the cumulative surface areas of both stimulus shoals were equal; however, qingbo showed a preference for the shoal with the larger cumulative surface area when the two stimulus shoals each had 3 individuals. In conclusion, the present study demonstrated that all four fish species relied only on non-numerical continuous quantity information for shoal selection, at least under a difficult task (i.e., 2 vs 3).


Assuntos
Comportamento de Escolha , Peixes/fisiologia , Comportamento Social , Animais , Comportamento Animal , Superfície Corporal , Sinais (Psicologia)
13.
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
14.
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
15.
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
16.
Am J Reprod Immunol ; 80(1): e12974, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29774963

RESUMO

PROBLEM: The development of the placenta and its functions are sensitive to infection and stress, which can activate the hypothalamic-pituitary-adrenal axis. Adrenally produced glucocorticoids are the body's primary mediators of the inflammatory and stress response. Although the glucocorticoid receptor (GR) is expressed in all human villous trophoblast tissue, the effect of glucocorticoids on placentation is not well understood. METHOD OF STUDY: Using microarray analysis, we identified the glucocorticoid-regulated transcriptional profile in the immortalized first-trimester extravillous trophoblast cell line Swan.71 (Sw.71). RESULTS: The synthetic glucocorticoid dexamethasone significantly regulated 3829 genes, including genes associated with cell movement, growth, and survival. SERPINE1, an inhibitor of trophoblast invasion, was induced by glucocorticoids in Sw.71 cells and is associated with the pathogenesis of preeclampsia. Glucocorticoid treatment induced recruitment of activated polymerase II and GR to the SERPINE1 promoter, suggesting a mechanism for transcriptional regulation. Functionally, glucocorticoid treatment inhibited cell proliferation, migration, and invasion. CONCLUSION: These findings suggest that glucocorticoids regulate extravillous trophoblast functions by altering the gene expression profile, which may contribute to the pathogenesis of reproductive disorders such as preeclampsia and IUGR.


Assuntos
Movimento Celular/efeitos dos fármacos , Glucocorticoides/metabolismo , Invasividade Neoplásica/patologia , Primeiro Trimestre da Gravidez/metabolismo , Transdução de Sinais/fisiologia , Trofoblastos/metabolismo , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Dexametasona/farmacologia , Feminino , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Primeiro Trimestre da Gravidez/genética , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcrição Genética/efeitos dos fármacos , Transcrição Genética/genética , Trofoblastos/efeitos dos fármacos
17.
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
18.
Ecotoxicol Environ Saf ; 157: 266-275, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29626640

RESUMO

Cd(II) is one of the most widespread and toxic heavy metals and seriously threatens plant growth, furthermore negatively affecting human health. For survival from this metal stress, plants always fight with Cd(II) toxicity by themselves or using other external factors. The effects of second metals copper (Cu(II)), zinc (Zn(II)) and calcium (Ca(II)) on the Cd(II)-affected root morphology, Cd(II) translocation and metabolic responses in Catharanthus roseus were investigated under hydroponic conditions. We found that the Cd-stressed plants displayed the browning and rot root symptom, excess H2O2 content, lipid peroxidation and Cd(II) accumulation in plants. However, the supplement with second metals largely alleviated Cd-induced toxicity, including browning and rot roots, oxidative stress and internal Cd(II) accumulation. The amended effects at metabolic and transcriptional levels involved in different second metals share either common or divergent strategies. They commonly repressed Cd uptake and promoted Cd(II) translocation from roots to shoots with divergent mechanisms. High Zn(II) could activate MTs expression in roots, while Cu(II) or Ca(II) did not under Cd(II) stress condition. The presence of Ca(II) under Cd stress condition largely initiated occurrence of lateral roots. We then grouped a metabolic diagram integrating terpenoid indole alkaloid (TIA) accumulation and TIA pathway gene expression to elucidate the metabolic response of C. roseus to Cd(II) alone or combined with second metals. The treatment with 100 Cd(II) alone largely promoted accumulation of vinblastine, vindoline, catharanthine and loganin, whereas depressed or little changed the expression levels of genes detected here, compared to 0 Cd(II) control. In the presence of Cd(II), the supplement with second metals displayed specific effect on different alkaloid. Among them, the metal Ca(II) is especially beneficial for serpentine accumulation, Zn(II) mainly promoted tabersonine production. However, the addition of Cu(II) commonly depressed accumulation of most alkaloids detected here. Generally, we presented different mechanisms by which the second metals used to alleviate Cd (II) toxicity. This plant has potential application in phytoremediation of Cd(II), due to relatively substantial accumulation of biomass, as well as secondary metabolites TIAs used as pharmaceutical materials when facing Cd stress.


Assuntos
Cádmio/toxicidade , Cálcio/farmacologia , Catharanthus/efeitos dos fármacos , Cobre/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Poluentes do Solo/toxicidade , Zinco/farmacologia , Alcaloides/metabolismo , Biodegradação Ambiental , Catharanthus/metabolismo , Interações de Medicamentos , Metalotioneína/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plantas Medicinais/efeitos dos fármacos , Plantas Medicinais/metabolismo , Solo/química , Poluentes do Solo/metabolismo
19.
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
20.
Nat Prod Res ; 32(15): 1863-1866, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29156967

RESUMO

In this study, we examined Vicia seeds using gas chromatography-mass spectrometry (GC-MS). The metabolic differences of seeds of twelve Vicia species were assessed. 184 metabolites were identified. Vicia species were classified via multivariate data analyses into four clusters. V. unijuga was most enriched in fatty acids and anthraquinones contents while highest levels of amino acids, alcohols and phenolic were in V. costata. Clustering analysis of biochemical profiles matched with the pervious phenotypic observation with all examined species from section Cracca grouped together under one sub-cluster, except for V. costata.


Assuntos
Sementes/química , Sementes/metabolismo , Vicia/metabolismo , Álcoois/análise , Aminoácidos/análise , Antraquinonas/análise , China , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Fenóis/análise , Vicia/química
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