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1.
Curr Med Sci ; 39(2): 337-342, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016531

RESUMO

Calcium carbonates are commonly administered as supplements for conditions of calcium deficiency. We report here pharmacokinetic characteristics of a novel formulation, calcium carbonate compound granules (CCCGs), forming complexes of calcium carbonate and calcium citrate in water. CCCGs were compared to a kind of commonly-used calcium carbonate D3 preparation (CC) in the market in 5-week-old mice that had been treated with omeprazole, to suppress gastric acid secretion, and in untreated control mice. The results showed that: (1) CCCGs had better water solubility than CC in vitro; (2) In control mice, calcium absorption rates after CCCGs administration were comparable to those after CC administration; (3) Inhibition of gastric acid secretion did not affect calcium absorption after CCCGs, but moderately decreased it after CC; (4) The presence of phytic acid or tannin did not affect calcium absorption rates after CCCGs but did for CC; and (5) In normal mice, CCCGs did not inhibit gastric emptying and intestinal propulsion, and did not alter the gastrointestinal hormones. The results suggest that CCCGs may be therapeutically advantageous over more commonly used calcium supplement formulations, particularly for adolescents, because of their stable calcium absorption characteristics and their relatively favorable adverse effect profile.


Assuntos
Carbonato de Cálcio/metabolismo , Ácido Gástrico/metabolismo , Animais , Cálcio na Dieta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
2.
Mol Oncol ; 13(4): 873-893, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30628173

RESUMO

Forkhead box transcription factor M1 (FOXM1) is a proliferation-associated transcription factor involved in tumorigenesis through transcriptional regulation of its target genes in various cells, including dendritic cells (DCs). Although previous work has shown that FOXM1 enhances DC maturation in response to house dust mite allergens, it is not known whether FOXM1 affects DC maturation in the context of tumor-specific immunity. In this study, we examined the central role of FOXM1 in regulating bone marrow-derived dendritic cell (BMDC) maturation phenotypes and function in pancreatic cancer and colon cancer. FOXM1 retarded maturation phenotypes of BMDCs, inhibited promotion of T-cell proliferation, and decreased interleukin-12 (IL-12) p70 in tumor-bearing mice (TBM). Notably, FOXM1 expression was epigenetically regulated by dimethylation on H3 lysine 79 (H3K79me2), a modification present in both tumor cells and BMDCs. Increased H3K79me2 enrichment was observed at the FOXM1 promoter in both BMDCs from TBM, and in BMDCs from wild-type mice cultured with tumor-conditioned medium that mimics the tumor microenvironment (TME). Furthermore, inhibition of the H3K79 methyltransferase DOT1L not only decreased enrichment of H3K79me2, but also downregulated expression of FOXM1 and partially reversed its immunosuppressive effects on BMDCs. Furthermore, we found that FOXM1 upregulated transcription of Wnt family number 5A (Wnt5a) in BMDCs in vitro; we also observed that exogenous Wnt5a expression abrogated BMDC maturation phenotypes by inhibiting FOXM1 and H3K79me2 modification. Therefore, our results reveal that upregulation of FOXM1 by H3K79me2 in pancreatic cancer and colon cancer significantly inhibits maturation phenotypes and function of BMDCs through the Wnt5a signaling pathway, and thus provide novel insights into FOXM1-based antitumor immunotherapy.

3.
Front Pharmacol ; 9: 187, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29556199

RESUMO

Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB). Pathway and functional enrichment analysis of these putative targets indicated that DGLHD obviously influenced NF-κB and PPAR signaling pathway. Consistently, DGLHD downregulated levels of ALT (alanine transaminase) and AST (aspartate transaminase), reduced production of proinflammatory cytokines-TNF (tumor necrosis factor) -α and IL (Interleukin) -1ß in serum and liver from mice with hepatic fibrosis, and inhibited hepatic stellate cell (HSC)-T6 cells proliferation. DGLHD decreased TGF (transforming growth factor) -ß1 and α-SMA (smooth muscle actin) expression as well, maintained MMP (matrix metalloprotein) 13-TIMP (tissue inhibitor of metalloproteinases) 1 balance, leading to mitigated ECM (extracellular matrix) deposition in vivo and in vitro. Moreover, our experimental data confirmed that the alleviated inflammation and ECM accumulation were pertinent to NF-κB inhibition and PPAR-γ activation. Overall, our results suggest that DGLHD aims at multiply targets and impedes the progression of hepatic fibrosis by ameliorating abnormal inflammation and ECM deposition, thereby serving as a novel regimen for treating hepatic fibrosis in clinic.

4.
Biomark Med ; 11(6): 419-426, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28379039

RESUMO

AIM: To investigate the changes and significance of circulating IL-39 in patients with acute coronary syndrome (ACS). PATIENTS & METHODS: Serum IL-39 levels in ACS patients and normal coronary arteries were measured. The correlations of IL-39 with high-sensitivity CRP, cTnI, N-terminal of the prohormone brain natriuretic peptide (NTproBNP) and left ventricular ejection fraction were investigated. RESULTS: The serum levels of IL-39 in ACS patients were significantly increased. IL-39 levels were positively correlated with NTproBNP, high-sensitivity CRP and cTnI, negatively correlated with left ventricular ejection fraction in ACS patients. The most significant correlation arose between serum IL-39 and NTproBNP in STEMI patients (r = 0.8309; p < 0.0001). CONCLUSION: Circulating level of IL-39 might be a predictor of cardiac systolic dysfunction in ST-segment elevation myocardial infarction patients.


Assuntos
Interleucinas/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Sístole/fisiologia , Disfunção Ventricular Esquerda/sangue , Síndrome Coronariana Aguda/complicações , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Volume Sistólico , Troponina I/sangue , Disfunção Ventricular Esquerda/complicações
5.
Plant Physiol ; 173(3): 1920-1932, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28126846

RESUMO

The brown planthopper (BPH) Nilaparvata lugens is one of the most destructive insect pests on rice (Oryza sativa) in Asia. After landing on plants, BPH rapidly accesses plant phloem and sucks the phloem sap through unknown mechanisms. We discovered a salivary endo-ß-1,4-glucanase (NlEG1) that has endoglucanase activity with a maximal activity at pH 6 at 37°C and is secreted into rice plants by BPH NlEG1 is highly expressed in the salivary glands and midgut. Silencing NlEG1 decreases the capacity of BPH to reach the phloem and reduces its food intake, mass, survival, and fecundity on rice plants. By contrast, NlEG1 silencing had only a small effect on the survival rate of BPH raised on artificial diet. Moreover, NlEG1 secreted by BPH did not elicit the production of the defense-related signal molecules salicylic acid, jasmonic acid, and jasmonoyl-isoleucine in rice, although wounding plus the application of the recombination protein NlEG1 did slightly enhance the levels of jasmonic acid and jasmonoyl-isoleucine in plants compared with the corresponding controls. These data suggest that NlEG1 enables the BPH's stylet to reach the phloem by degrading celluloses in plant cell walls, thereby functioning as an effector that overcomes the plant cell wall defense in rice.


Assuntos
Endo-1,3(4)-beta-Glucanase/metabolismo , Comportamento Alimentar/fisiologia , Hemípteros/fisiologia , Proteínas de Insetos/metabolismo , Oryza/parasitologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Parede Celular/metabolismo , Celulose/metabolismo , Ciclopentanos/metabolismo , Endo-1,3(4)-beta-Glucanase/classificação , Endo-1,3(4)-beta-Glucanase/genética , Fertilidade/genética , Regulação Enzimológica da Expressão Gênica , Hemípteros/enzimologia , Hemípteros/genética , Interações Hospedeiro-Parasita , Proteínas de Insetos/classificação , Proteínas de Insetos/genética , Oxilipinas/metabolismo , Floema/parasitologia , Filogenia , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Saliva/enzimologia , Homologia de Sequência de Aminoácidos
6.
Sci Rep ; 7: 40498, 2017 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-28098179

RESUMO

The brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), a major pest of rice in Asia, is able to successfully puncture sieve tubes in rice with its piercing stylet and then to ingest phloem sap. How BPH manages to continuously feed on rice remains unclear. Here, we cloned the gene NlSEF1, which is highly expressed in the salivary glands of BPH. The NlSEF1 protein has EF-hand Ca2+-binding activity and can be secreted into rice plants when BPH feed. Infestation of rice by BPH nymphs whose NlSEF1 was knocked down elicited higher levels of Ca2+ and H2O2 but not jasmonic acid, jasmonoyl-isoleucine (JA-Ile) and SA in rice than did infestation by control nymphs; Consistently, wounding plus the recombination protein NlSEF1 suppressed the production of H2O2 in rice. Bioassays revealed that NlSEF1-knockdown BPH nymphs had a higher mortality rate and lower feeding capacity on rice than control nymphs. These results indicate that the salivary protein in BPH, NlSEF1, functions as an effector and plays important roles in interactions between BPH and rice by mediating the plant's defense responses.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Motivos EF Hand , Hemípteros/metabolismo , Proteínas de Insetos/metabolismo , Oryza/imunologia , Oryza/parasitologia , Glândulas Salivares/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/isolamento & purificação , Ciclopentanos/metabolismo , Citosol/metabolismo , Comportamento Alimentar , Feminino , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Peróxido de Hidrogênio/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/genética , Proteínas de Insetos/isolamento & purificação , Isoleucina/análogos & derivados , Isoleucina/metabolismo , Larva/fisiologia , Oryza/genética , Oxilipinas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ácido Salicílico/metabolismo
7.
Colloids Surf B Biointerfaces ; 143: 455-462, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27037783

RESUMO

In this study, novel chitosan-coated deformable liposomes (DL-CS) were proposed as an ocular drug delivery system to prolong pre-corneal retention, and improve transcorneal penetration and absorption. Flurbiprofen-loaded deformable liposomes (FP-DL) were prepared by a modified ethanol injection method and then coated with chitosan. Both DL and DL-CS exhibited a homogeneous particle size distribution, high encapsulation efficiency and good stability. After coating with 0.1% CS, the zeta potential was shifted from negative to positive. The apparent permeability coefficient of FP-DL-0.1% CS evaluated using isolated rabbit corneas was 1.29-, 1.95- and 4.59- fold greater than that of uncoated FP-DL, conventional liposomes and FP solution (P<0.01), respectively. The in vivo pre-corneal retention time and elimination dynamics were assessed using gamma scintigraphy technology. The area under the remaining activity-time of FP-DL-0.1% CS was prolonged 2.84- and 1.53-fold compared with that of the FP solution and FP-DL groups, respectively. Moreover, the ocular irritation test in vivo revealed that DL-0.1% CS produced no ocular damage or abnormal clinical signs. These results indicate that DL-CS appears to be a novel ophthalmic drug delivery strategy with the potential to overcome the limitations of conventional eye drops.


Assuntos
Quitosana/química , Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Flurbiprofeno/farmacocinética , Lipossomos/farmacocinética , Administração Oftálmica , Animais , Córnea/metabolismo , Composição de Medicamentos , Liberação Controlada de Fármacos , Flurbiprofeno/metabolismo , Lipossomos/química , Lipossomos/metabolismo , Masculino , Tamanho da Partícula , Permeabilidade , Coelhos , Técnicas de Cultura de Tecidos
8.
Sci Rep ; 6: 21148, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26892186

RESUMO

Acori Graminei Rhizoma is well known for the beneficial effects on CNS disorders in traditional medicine. Though it is frequently prescribed in formulations for brain tumors, the anti-glioma effect has not been examined. We used volatile oil of Acori Graminei Rhizoma (VOA) and human glioblastoma multiforme (GBM) cells in this study. We found that VOA exhibited greater growth suppression in p53 wild-type cells than p53 mutant cells and very low effect on fibroblasts and human glial HEB cells. Apoptosis was triggered by VOA with a caspase-dependent way in p53 wild-type A172 cells, while a caspase-independent way in p53 mutant U251 cells. Meanwhile, both A172 and U251 cells treated by VOA displayed autophagic features. Furthermore, p53 decrease was observed along with VOA-induced apoptosis and autophagy in A172 cells. VOA-induced autophagy was mediated through a p53/AMPK/mTOR signaling pathway in A172 cells, while an mTOR-independent signaling pathway in U251 cells. Finally, blockage of autophagy potentiated the proapoptotic effect in both A172 and U251 cells, indicating a protective role of autophagy in VOA-induced cell death. Together, VOA exhibited anti-tumor activity in human GBM cells and induced apoptotic cell death and protective autophagy, which is cell type specific and dependent on p53 status.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Óleos Voláteis/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/química , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Camundongos , Mutação , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/genética
9.
PLoS One ; 9(2): e88528, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24533099

RESUMO

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens (Stål), one of the most serious rice insect pests in Asia, can quickly overcome rice resistance by evolving new virulent populations. The insect fat body plays essential roles in the life cycles of insects and in plant-insect interactions. However, whether differences in fat body transcriptomes exist between insect populations with different virulence levels and whether the transcriptomic differences are related to insect virulence remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed transcriptome-wide analyses on the fat bodies of two BPH populations with different virulence levels in rice. The populations were derived from rice variety TN1 (TN1 population) and Mudgo (M population). In total, 33,776 and 32,332 unigenes from the fat bodies of TN1 and M populations, respectively, were generated using Illumina technology. Gene ontology annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology classifications indicated that genes related to metabolism and immunity were significantly active in the fat bodies. In addition, a total of 339 unigenes showed homology to genes of yeast-like symbionts (YLSs) from 12 genera and endosymbiotic bacteria Wolbachia. A comparative analysis of the two transcriptomes generated 7,860 differentially expressed genes. GO annotations and enrichment analysis of KEGG pathways indicated these differentially expressed transcripts might be involved in metabolism and immunity. Finally, 105 differentially expressed genes from YLSs and Wolbachia were identified, genes which might be associated with the formation of different virulent populations. CONCLUSIONS/SIGNIFICANCE: This study was the first to compare the fat-body transcriptomes of two BPH populations having different virulence traits and to find genes that may be related to this difference. Our findings provide a molecular resource for future investigations of fat bodies and will be useful in examining the interactions between the fat body and virulence variation in the BPH.


Assuntos
Corpo Adiposo/fisiologia , Hemípteros/genética , Hemípteros/microbiologia , Transcriptoma , Animais , Carboidratos/química , DNA Complementar/metabolismo , Feminino , Perfilação da Expressão Gênica , Biblioteca Gênica , Genoma , Metabolismo dos Lipídeos , Oryza , RNA Mensageiro/metabolismo , Transdução de Sinais , Especificidade da Espécie , Virulência , Wolbachia/genética , Xenobióticos/química
10.
PLoS One ; 8(11): e79612, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24244529

RESUMO

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens (Stål), a destructive rice pest in Asia, can quickly overcome rice resistance by evolving new virulent populations. Herbivore saliva plays an important role in plant-herbivore interactions, including in plant defense and herbivore virulence. However, thus far little is known about BPH saliva at the molecular level, especially its role in virulence and BPH-rice interaction. METHODOLOGY/PRINCIPAL FINDINGS: Using cDNA amplification in combination with Illumina short-read sequencing technology, we sequenced the salivary-gland transcriptomes of two BPH populations with different virulence; the populations were derived from rice variety TN1 (TN1 population) and Mudgo (M population). In total, 37,666 and 38,451 unigenes were generated from the salivary glands of these populations, respectively. When combined, a total of 43,312 unigenes were obtained, about 18 times more than the number of expressed sequence tags previously identified from these glands. Gene ontology annotations and KEGG orthology classifications indicated that genes related to metabolism, binding and transport were significantly active in the salivary glands. A total of 352 genes were predicted to encode secretory proteins, and some might play important roles in BPH feeding and BPH-rice interactions. Comparative analysis of the transcriptomes of the two populations revealed that the genes related to 'metabolism,' 'digestion and absorption,' and 'salivary secretion' might be associated with virulence. Moreover, 67 genes encoding putative secreted proteins were differentially expressed between the two populations, suggesting these genes may contribute to the change in virulence. CONCLUSIONS/SIGNIFICANCE: This study was the first to compare the salivary-gland transcriptomes of two BPH populations having different virulence traits and to find genes that may be related to this difference. Our data provide a rich molecular resource for future functional studies on salivary glands and will be useful for elucidating the molecular mechanisms underlying BPH feeding and virulence differences.


Assuntos
Hemípteros/genética , Glândulas Salivares/metabolismo , Transcriptoma , Virulência/genética , Animais , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Hemípteros/metabolismo , Hemípteros/patogenicidade , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular , Oryza/parasitologia
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