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1.
BMC Plant Biol ; 23(1): 516, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37880597

RESUMO

BACKGROUND: Dendrobium nobile has unique growth environment requirements, and unstable yields and high management costs are the key factors restricting the development of its imitation wild cultivation industry. The present study explored the effects of different associated bryophyte species on the yield and quality of D. nobile to clarify the dominant bryophyte species associated with D. nobile and to provide a scientific basis for the rational cultivation and quality evaluation of D. nobile. RESULTS: The growth of D. nobile was closely related to the microenvironment of the Danxia stone, and the different associated bryophytes had different effects on D. nobile growth. There was a rich variety of bryophytes associated with D. nobile, with a total of 15 families, 24 genera and 31 species of bryophytes identified in the study area, including 13 families, 22 genera and 29 species of mosses and 2 families, 2 genera and 2 species of liverworts, and mosses predominated in the association with D. nobile. Usually, 3-9 species of bryophytes were growing in association with D. nobile, among which associations of 5-6 bryophytes species were more common, and the bryophytes associated with D. nobile were only related to the species to which they belonged. The dry matter accumulation, quality and mineral content of D. nobile differed significantly among different bryophyte species. The coefficients of variation of dry matter accumulation, dendrobine content and content of 11 mineral elements of D. nobile in the 35 sample quadrats were 25.00%, 21.08%, and 11.33-57.96%, respectively. The biomass, dendrobine content and mineral content of D. nobile were analysed by principal component analysis (PCA) and membership function. The results showed that each evaluation method initially screened Trachycystis microphylla and Leucobryum juniperoideum as the dominant associated bryophytes in the preliminary identification analysis, and the frequency of occurrence and coverage of the two bryophytes were significantly higher than those of the remaining bryophytes. It was determined that T. microphylla and L. juniperoideum were the dominant associated bryophytes. CONCLUSIONS: There is a rich variety of bryophytes associated with D. nobile. The yield and quality of D. nobile differed significantly among different bryophyte species. T. microphylla and L. juniperoideum were the dominant associated bryophytes, and were the two bryophytes associated with D. nobile through mixed growth.


Assuntos
Briófitas , Dendrobium , Humanos , Biomassa , Minerais
2.
Zhongguo Zhong Yao Za Zhi ; 48(3): 625-635, 2023 Feb.
Artigo em Zh | MEDLINE | ID: mdl-36872225

RESUMO

This study explored the feasibility of mineral element content and ratios of nitrogen isotopes to discriminate the cultivation mode of Dendrobium nobile in order to provide theoretical support for the discrimination of the cultivation mode of D. nobile. The content of 11 mineral elements(N, K, Ca, P, Mg, Na, Fe, Cu, Zn, Mn, and B) and nitrogen isotope ratios in D. nobile and its substrate samples in three cultivation methods(greenhouse cultivation, tree-attached cultivation, and stone-attached cultivation) were determined. According to the analysis of variance, principal component analysis, and stepwise discriminant analysis, the samples of different cultivation types were classified. The results showed that the nitrogen isotope ratios and the content of elements except for Zn were significantly different among different cultivation types of D. nobile(P<0.05). The results of correlation analysis showed that the nitrogen isotope ratios, mineral element content, and effective component content in D. nobile were correlated with the nitrogen isotope ratio and mineral element content in the corresponding substrate samples to varying degrees. Principal component analysis can preliminarily classify the samples of D. nobile, but some samples overlapped. Through stepwise discriminant analysis, six indicators, including δ~(15)N, K, Cu, P, Na, and Ca, were screened out, which could be used to establish the discriminant model of D. nobile cultivation methods, and the overall correct discrimination rates after back-substitution test, cross-check, and external validation were all 100%. Therefore, nitrogen isotope ratios and mineral element fingerprints combined with multivariate statistical analysis could effectively discriminate the cultivation types of D. nobile. The results of this study provide a new method for the identification of the cultivation type and production area of D. nobile and an experimental basis for the quality evaluation and quality control of D. nobile.


Assuntos
Dendrobium , Minerais , Análise Discriminante , Análise Multivariada , Isótopos de Nitrogênio
3.
BMC Genomics ; 23(1): 195, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35272619

RESUMO

BACKGROUND: The investigation of molecular mechanisms involved in polysaccharides and saponin metabolism is critical for genetic engineering of Polygonatum cyrtonema Hua to raise major active ingredient content. Up to now, the transcript sequences are available for different tissues of P. cyrtonema, a wide range scanning about temporal transcript at different ages' rhizomes was still absent in P. cyrtonema. RESULTS: Transcriptome sequencing for rhizomes at different ages was performed. Sixty-two thousand six hundred thirty-five unigenes were generated by assembling transcripts from all samples. A total of 89 unigenes encoding key enzymes involved in polysaccharide biosynthesis and 56 unigenes encoding key enzymes involved in saponin biosynthesis. The content of total polysaccharide and total saponin was positively correlated with the expression patterns of mannose-6-phosphate isomerase (MPI), GDP-L-fucose synthase (TSTA3), UDP-apiose/xylose synthase (AXS), UDP-glucose 6-dehydrogenase (UGDH), Hydroxymethylglutaryl CoA synthase (HMGS), Mevalonate kinase (MVK), 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (ispF), (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ispG), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ispH), Farnesyl diphosphate synthase (FPPS). Finally, a number of key genes were selected and quantitative real-time PCR were performed to validate the transcriptome analysis results. CONCLUSIONS: These results create the link between polysaccharides and saponin biosynthesis and gene expression, provide insight for underlying key active substances, and reveal novel candidate genes including TFs that are worth further exploration for their functions and values.


Assuntos
Polygonatum , Saponinas , Perfilação da Expressão Gênica , Genes de Plantas , Polygonatum/genética , Polissacarídeos , Saponinas/genética
4.
Biochem Biophys Res Commun ; 613: 53-60, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35533600

RESUMO

Enzalutamide is an effective drug for the treatment of castration-resistant prostate cancer (CRPC), but acquired enzalutamide resistance is usually unavoidable within the short term in many patients. Lycopene, a safe and effective phytochemical, has been documented to have anticancer activity in a variety of tumors, especially for prostate cancer (PCa). The aim of this study was to provide data support for the combination of lycopene and enzalutamide in the treatment of CRPC. To this end, tissues from patients with primary prostate cancer (PPC) and CRPC were examined by immunohistochemical analysis and found that p-AKT and p-EZH2 were overexpressed in CRPC. Furthermore, Kaplan-Meier survival analysis showed that the high expression of p-AKT and p-EZH2 may be related to the poor prognosis of patients. In addition, the expression of p-AKT, p-EZH2 and androgen receptor (AR) were significantly down-regulated in 22RV1 and C4-2B cells and the proliferation and invasion of CRPC cells were inhibited after treatment with lycopene, while SC79 (an AKT agonist) markedly rescue this effect. Of note, a combination of lycopene and enzalutamide significantly inhibited the proliferation and invasion of CRPC cells in vitro, as well as tumor growth and bone metastasis in vivo. These results suggest that the enhanced antitumor effects of enzalutamide by lycopene may be related to the reduction of AR protein levels through lycopene-mediated inhibition of AKT/EZH2 pathway, which may provide a new approach to improve the efficacy of enzalutamide in CRPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Proteína Potenciadora do Homólogo 2 de Zeste , Licopeno , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Proteínas Proto-Oncogênicas c-akt , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzamidas/administração & dosagem , Benzamidas/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Licopeno/administração & dosagem , Licopeno/farmacologia , Masculino , Nitrilas/administração & dosagem , Nitrilas/farmacologia , Feniltioidantoína/administração & dosagem , Feniltioidantoína/farmacologia , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Androgênicos/metabolismo , Transdução de Sinais
5.
Prostate ; 81(16): 1320-1328, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34590739

RESUMO

OBJECTIVE: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men which is associated with profound metabolic changes. Systematic analysis of the metabolic alterations and identification of new biomarkers may benefit PCa diagnosis and a deep understanding of the pathological mechanism. The purpose of this study was to determine the metabolic features of PCa. METHODS: Plasma and urine metabolites from 89 prostate cancer (PCa) patients, 84 benign prostatic hyperplasia (BPH) patients, and 70 healthy males were analyzed using LC-MS/MS and GC-MS. The Orthogonalised Partial Least Squares Discriminant Analysis (OPLS-DA) was used to find the significantly changed metabolites. The clinical value of the candidate markers was examined by receiver operating characteristic curve analysis and compared with prostate-specific antigen (PSA). RESULTS: Multivariate statistical analyses found a series of altered metabolites, which related to the urea cycle, tricarboxylic acid cycle (TCA), fatty acid metabolism, and the glycine cleavage system. Plasma Glu/Gln showed the highest predictive value (AUC = 0.984) when differentiating PCa patients from healthy controls, with a higher sensitivity than PSA (96.6% vs. 94.4%). Both Glu/Gln and PSA displayed a low specificity when differentiating PCa patients from BPH patients (<53.2%), while the combination of Glu/Gln and PSA can further increase the diagnostic specificity to 66.9%. CONCLUSIONS: The present study showed the metabolic features of PCa, provided strong evidence that the amide nitrogen and the energy metabolic pathways could be a valuable source of markers for PCa. Several candidate markers identified in this study were clinically valuable for further assessment.


Assuntos
Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nitrogênio/metabolismo , Próstata , Hiperplasia Prostática , Neoplasias da Próstata , Idoso , Metabolismo Energético , Humanos , Masculino , Redes e Vias Metabólicas , Metabolômica/métodos , Tamanho do Órgão , Próstata/diagnóstico por imagem , Próstata/metabolismo , Próstata/patologia , Antígeno Prostático Específico/análise , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Hiperplasia Prostática/urina , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Reprodutibilidade dos Testes
6.
Br J Cancer ; 124(1): 247-258, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33024272

RESUMO

BACKGROUND: The role of HOX transcript antisense RNA (HOTAIR) has been proven to be important in tumorigenesis. However, how this molecule promotes metastasis and invasion in PCa is still unclear. METHODS: The relationship between HOTAIR and hepatocellular adhesion molecule (hepaCAM) in PCa was identified by immunohistochemistry, immunofluorescence, plasmid transfection, quantitative real-time PCR and immunoblotting. The regulatory effects of HOTAIR on hepaCAM and MAPK signalling and their key roles in PCa metastasis were investigated in vitro. RESULTS: The expression of HOTAIR was inversely correlated with hepaCAM in the blood and tissue of PCa patients. Here, hepaCAM was identified as a novel target gene of HOTAIR and was critical for the invasiveness of PCa. HOTAIR recruited PRC2 to the hepaCAM promoter, resulting in high levels of H3K27me3 and the absence of hepaCAM with an abnormally activated MAPK pathway. Both HOTAIR depletion and EZH2 inhibition could induce hepaCAM re-expression with inhibitory MAPK signalling and decrease the invasive and metastatic capabilities of PCa cells. CONCLUSIONS: This study demonstrates that HOTAIR promotes invasion and metastasis of PCa by decreasing the inhibitory effect of hepaCAM on MAPK signalling. Therefore, the HOTAIR/hepaCAM/MAPK axis may provide a new avenue towards therapeutic strategies and prognostic indicators for advanced prostate cancer.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Invasividade Neoplásica/genética , Neoplasias da Próstata/patologia , RNA Longo não Codificante/metabolismo , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Neoplasias da Próstata/genética
7.
Chem Biodivers ; 18(8): e2001001, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34156157

RESUMO

The present study aimed to explore the therapeutic effects of the main active ingredients of Atractylodes macrocephala on the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced mouse colitis model. TNBS-induced colitis was established in mice, which were treated with 8-ß-Hydroxyasterolide (Atractylenolide III) for 14 days. The body weight of the mice in the middle and high dose groups of Atractylenolide III was increased compared with that of the model group. The disease activity index score was significantly reduced. The activity levels of myeloperoxidase were significantly decreased following increase in the dosage of Atractylenolide III, as determined by histological analysis. Moreover, Atractylenolide III downregulated the expression levels of the inflammatory factors interleukin-1ß and tumor necrosis factor-α, and greatly suppressed the levels of the pro-oxidant markers, reactive oxygen species and malondialdehyde, while enhancing the expression levels of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. The protein expression levels of formyl peptide receptor 1 (FPR1) and nuclear respiratory factor 2 (Nrf2) were upregulated in the colonic tissues of TNBS-treated mice. This effect was effectively reversed by Atractylenolide III treatment. In vivo studies indicated that TNBS alone induced a decrease in the abundance of lactobacilli and in the biodiversity of the colon. In conclusion, the present study suggested that Atractylenolide III attenuated TNBS-induced acute colitis by regulating oxidative stress via the FPR1 and Nrf2 pathways and by affecting the development of intestinal flora.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Lactonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Interleucina-1beta/metabolismo , Lactonas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ácido Trinitrobenzenossulfônico/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
J Cell Physiol ; 235(11): 8546-8557, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32383180

RESUMO

Phospholipase C-ε (PLCε) is frequently overexpressed in tumors and plays an important role in the regulation of tumorigenesis. Although great progress has been made in understanding biological roles of PLCε, the relevant molecular mechanisms underlying its pro-tumor activity remain largely unclear. Here, we demonstrated that PLCε knockdown reduced cell metastasis, glucose consumption and lactate production in a manner that depended on hypoxia inducible factor 1α (HIF-1α) expression in prostate cancer cells. Interestingly, our findings showed that the expression levels of PLCε were positively associated with those of HIF-1α in clinical prostate carcinoma samples. Knockdown of PLCε impaired HIF-1α levels and transcriptional activity by regulating the extracellular-signal-regulated kinase pathway, and blocking HIF-1α nuclear translocation. Furthermore, PLCε could interact with the von Hippel-Lindau E3 ligase complex to modulate the stability of HIF-1α. Collectively, our findings demonstrate that PLCε could be a crucial positive regulator of HIF-1α, which would promote PLCε-enhanced tumorigenesis.


Assuntos
Fosfoinositídeo Fosfolipase C/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais/fisiologia , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Metástase Neoplásica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Strahlenther Onkol ; 196(6): 505-514, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31828393

RESUMO

PURPOSE: Severe acute radiation pneumonitis (SARP) is a life-threatening complication of thoracic radiotherapy. Pre-treatment pulmonary function (PF) may influence its incidence. We have previously reported on the incidence of SARP among patients with moderate pulmonary dysfunction who received definitive concurrent chemoradiotherapy (dCCRT) for non-small cell lung cancer (NSCLC). METHODS: The clinical outcomes, dose-volume histograms (DVH), and PF parameters of 122 patients (forced expiratory volume in 1 s [FEV1%]: 60-69%) receiving dCCRT between 2013 and 2019 were recorded. SARP was defined as grade ≥3 RP occurring during or within 3 months after CCRT. Logistic regression, receiver operating characteristics curves (ROC), and hazard ratio (HR) analyses were performed to evaluate the predictive value of each factor for SARP. RESULTS: Univariate and multivariate analysis indicated that the ratio of carbon monoxide diffusing capacity (DLCO%; odds ratio [OR]: 0.934, 95% confidence interval [CI] 0.896-0.974, p = 0.001) and mean lung dose (MLD; OR: 1.002, 95% CI 1.001-1.003, p = 0.002) were independent predictors of SARP. The ROC AUC of combined DLCO%/MLD was 0.775 (95% confidence interval [CI]: 0.688-0.861, p = 0.001), with a sensitivity and specificity of 0.871 and 0.637, respectively; this was superior to DLCO% (0.656) or MLD (0.667) alone. Compared to the MLD-low/DLCO%-high group, the MLD-high/DLCO%-low group had the highest risk for SARP, with an HR of 9.346 (95% CI: 2.133-40.941, p = 0.003). CONCLUSION: The DLCO% and MLD may predict the risk for SARP among patients with pre-treatment moderate pulmonary dysfunction who receive dCCRT for NSCLC. Prospective studies are needed to validate our findings.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Neoplasias Pulmonares/terapia , Pulmão/efeitos da radiação , Pneumonite por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Testes de Função Respiratória , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Etoposídeo/administração & dosagem , Feminino , Humanos , Modelos Logísticos , Pulmão/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Paclitaxel/administração & dosagem , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Testes de Função Respiratória/estatística & dados numéricos , Estudos Retrospectivos , Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
10.
Med Sci Monit ; 26: e924328, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32696762

RESUMO

BACKGROUND Metabolic reprogramming is a common characteristic of numerous kinds of tumors, including prostate cancer (PCa). Tumor metabolism such as lipid metabolism provides sufficient lipids for tumor cell division and rapid growing as well as a vital source for formation of new cellular membranes. Phospholipase Cε (PLCε) is an oncogene that can drive proliferation, progression, and lipid metabolism of tumors, but its effect in lipid metabolism of PCa is not clear. MATERIAL AND METHODS Benign prostatic hyperplasia (BPH) and PCa tissue specimens were assessed for SREBP-1, FASN, and PLCε by immunohistochemistry, and PLCε was knocked-down by a lentiviral short hairpin RNA. The mRNA and protein level expression of related factors were tested by qPCR and Western blot analyses. Cell proliferation was assessed by clone formation, CCK-8, and Ki-67 assays. Nile red and oil red O staining were performed to detect endogenous lipid levels. Immunofluorescence was used to localize the protein of SREBP-1. Finally, a tumor xenograft assay of nude mice was performed to assess the role of PLCε in prostate tumor generation. RESULTS We found that overexpression of PLCε indicates low PFS in PCa and is involved in metastasis of PCa, and that the PLCε/AMPK/SREBP-1 signaling network promotes the progression of PCa through lipid metabolism in vivo and in vitro. CONCLUSIONS This study is the first to discover the lethal role of PLCε in lipid metabolism and malignant behavior of PCa, elucidation PCa occurrence and progression.


Assuntos
Metabolismo dos Lipídeos/fisiologia , Fosfoinositídeo Fosfolipase C/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Nus , Fosfoinositídeo Fosfolipase C/fisiologia , Próstata/citologia , RNA Mensageiro/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Cell Physiol ; 234(9): 15472-15486, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30684266

RESUMO

Most prostate cancers (Pcas) develop into castration-resistant prostate cancer (CRPC) after receiving androgen deprivation therapy (ADT). The expression levels of PLCε and wnt3a are increased in Pca and regulate androgen receptor (AR) activity. However, the biological function and mechanisms of PLCε and wnt3a in CRPC remain unknown. In this study, we found that the expression levels of PLCε, wnt3a, and AR were significantly increased in CRPC tissues as well as bicalutamide-resistant-LNCaP and enzalutamide-resistant-LNCaP cells. In addition, PLCε knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and enzalutamide by inhibiting the activity of the wnt3a/ß-catenin/AR signaling axis. Interestingly, the resistance of LNCaP cells docetaxel is related to PLCε but not the wnt3a/ß-catenin pathway. We also found that the combination of PLCε knockdown and enzalutamide treatment synergistically suppressed cell proliferation, tumor growth, and bone metastasis using in vitro and in vivo experiments. Our study revealed that PLCε is involved in the progression of drug-resistance in CRPC and could be a new target for the treatment of CRPC.

12.
Med Sci Monit ; 25: 4438-4449, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31201297

RESUMO

BACKGROUND Primary therapy for patients with advanced prostate cancer (PCa) consists of androgen deprivation therapy targeting the androgen receptor (AR) axis. However, most tumors progress to castration-resistant prostate cancer (CRPC) within 18-24 months. The purpose of the present study was to investigate the mechanisms through which PCa acquires drug resistance after long-term treatment with AR antagonists. MATERIAL AND METHODS Online database analysis and bioinformatics analysis were performed to identify signaling activated during anti-androgen treatment. MTT assay was used to detect cell viability. RT-qPCR was performed to examine the mRNA expression of the indicated genes. Colony formation assay was performed to observe cell proliferation. Transwell assay was conducted to demonstrate invasive ability. Protein levels were determined by Western blot analysis and immunofluorescence assays. RESULTS An online database search and bioinformatics analysis indicated that bone morphogenetic protein (BMP)-6/SMAD signaling was activated in enzalutamide-resistant LNCaP cells. Furthermore, this signaling interaction was experimentally verified in bicalutamide- and enzalutamide-resistant LNCaP cells, which may be regulated by phospholipase C (PLC)ε and induced cell proliferation and invasion. Of note, a positive correlation was observed between PLCε and BMP-6 in CRPC tissue samples, which may promote bone metastasis and suggests a poor prognosis. CONCLUSIONS The present results suggest that targeting of PLCε/BMP-6/SMAD signaling may increase the sensitivity of CRPC to AR antagonists and inhibit tumor progression.


Assuntos
Antagonistas de Receptores de Andrógenos/administração & dosagem , Proteína Morfogenética Óssea 6/metabolismo , Fosfoinositídeo Fosfolipase C/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Biologia Computacional/métodos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/genética , Transdução de Sinais/efeitos dos fármacos
13.
Molecules ; 24(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362394

RESUMO

The genus Periploca belongs to the family Apocynaceae, which is composed of approximately ten species of plants according to incomplete statistics. Most of these plants serve as folk medicines with a long history, especially Periploca sepium and Periploca forrestii. The botanical classifications, chemical constituents, biological activities and toxicities of the genus Periploca were summarized in the literature from 1897 to early 2019. Though the botanical classification of this genus is controversial, these species are well-known to be rich sources of diverse and complex natural products-above all, cardiac steroids and C21 pregnane steroids with special structures and obvious pharmacological activities. The various crude extracts and 314 isolated metabolites from this genus have attracted much attention in intensive biological studies, indicating that they are equipped with cardiotonic, anti-inflammatory, immunosuppressive, antitumor, antimicrobial, antioxidant, insecticidal and other properties. It is noteworthy that some cardiac glycosides showed hepatotoxicity and cardiotoxicity at certain doses. Therefore, in view of the medical and agricultural value of the genus Periploca, in-depth investigations of the pharmacology in vivo, the mechanisms of biological actions, and the pharmacokinetics of the active ingredients should be carried out in the future. Moreover, in order to ensure the safety of clinical medication, the potential toxicities of cardiac glycosides or other compounds should also be paid attention. This systematic review provides an important reference base for applied research on pharmaceuticals and pesticides from this genus.


Assuntos
Periploca/química , Periploca/classificação , Animais , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Testes de Toxicidade
14.
Med Sci Monit ; 24: 254-263, 2018 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-29330357

RESUMO

BACKGROUND Phospholipase Cε (PLCε), a member of the plc family, has been extensively studied to reveal its role in the regulation of different cell functions, but understanding of the underlying mechanisms remains limited. In the present study, we explored the effects of PLCε on PTEN (phosphatase and tensin homolog deleted on chromosome 10) in cell proliferation in prostate cancer cells. MATERIAL AND METHODS We assessed PLCε and PTEN expression in human benign prostate tissues compared to prostate cancer tissues by immunohistochemistry. Lentivirus-shPLCε (LV-shPLCε) was designed to silence PLCε expression in DU145 and PC3 cell lines, and the effectiveness was tested by qRT-PCR and Western blotting. MTT assay and colony formation assay were conducted to observe cell proliferation. Western blotting and immunofluorescence assays were used to detect changed PTEN expression in DU145. RESULTS We observed that PLCε expression was reduced in human benign prostate tissues compared to prostate cancer tissues, while PTEN expression showed the opposite trend. Silencing of the PLCε gene significantly inhibited cell proliferation in DU145 and PC3 cell lines. DU145 is a PTEN-expressing cell, while PC3 is PTEN-deficient. After infection by LV-shPLCε, we noticed that PTEN expression was up-regulated in DU145 cells but not in PC3 cells. Furthermore, we found that PLCε gene knockdown decreased P-AKT protein levels, but AKT protein levels were not affected. Immunofluorescence assays showed that PTEN expression had an intracellular distribution change in the DU145 cell line, and Western blot analysis showed that PTEN was obviously up-regulated in cell nucleus and cytoplasm. CONCLUSIONS PLCε is an oncogene, and knockdown of expression of PLCe inhibits PCa cells proliferation via the PTEN/AKT signaling pathway.


Assuntos
PTEN Fosfo-Hidrolase/metabolismo , Fosfoinositídeo Fosfolipase C/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Espaço Intracelular/metabolismo , Lentivirus/metabolismo , Masculino , Pessoa de Meia-Idade , Fosfoinositídeo Fosfolipase C/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Regulação para Cima/genética
15.
Tumour Biol ; 37(8): 10731-43, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26873485

RESUMO

The aim of this study was to explore the correlation between hepatocyte cell adhesion molecule (hepaCAM) and SMAD family member 2/3 (SMAD2/3) in bladder carcinoma, and the involvement of the SMAD2/3 pathway in hepaCAM-induced tumor apoptosis. Immunohistochemistry was used to measure hepaCAM and p-SMAD2/3 protein levels in bladder cancer tissues. Flow cytometry and Hoechst staining were used to study the effect of hepaCAM on cellular apoptosis. Western blot was employed to determine the expression of hepaCAM and SMAD2/3/caspase pathway molecules using a hepaCAM overexpression adenovirus, a caspase inhibitor (Z-VAD-FMK), and a SMAD2/3 activator (transforming growth factor (TGF)-ß1), respectively. Translocation of p-SMAD2/3 was measured by immunofluorescence and western blot. HepaCAM proteins were significantly decreased (P < 0.05), while p-SMAD2/3 proteins were remarkably increased (P < 0.05) in bladder carcinoma compared to adjacent tissues. However, the low hepaCAM and high p-SMAD2/3 were not statistically associated with clinicopathological characteristics of the patients. A negative linear correlation between hepaCAM and p-SMAD2/3 was observed according to Pearson analysis (r = -0.712/-0.724, P = 0.008/0.011). Overexpression of hepaCAM activated caspase 3/8/9 and downregulated poly-ADP ribose polymerase (PARP) and p-SMAD2/3. Treatment of bladder cancer cells with Z-VAD-FMK + hepaCAM significantly downregulated procaspase 3/8/9 and PARP and induced cellular apoptosis, compared with that using Z-VAD-FMK alone. Similarly, combined treatment of TGF-ß1 + hepaCAM significantly downregulated p-SMAD2/3, procaspase 3/8/9, and PARP and induced apoptosis of bladder cancer cells, compared with TGF-ß1 alone. Overexpression of hepaCAM prevented the p-SMAD2/3 translocation from the cytoplasm to the nucleus in bladder cancer cells BIU-87 and T24. Our findings uncover that the p-SMAD2/3 pathway is critical for hepaCAM-induced cancer cell apoptosis and provide valuable insights for current and future Ad-hepaCAM and p-SMAD2/3 clinical trials.


Assuntos
Carcinoma de Células de Transição/metabolismo , Proteínas de Neoplasias/fisiologia , Proteínas/fisiologia , Proteína Smad2/fisiologia , Proteína Smad3/fisiologia , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Clorometilcetonas de Aminoácidos/farmacologia , Apoptose/fisiologia , Carcinoma de Células de Transição/patologia , Caspases/biossíntese , Caspases/genética , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Poli(ADP-Ribose) Polimerases/biossíntese , Poli(ADP-Ribose) Polimerases/genética , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Neoplasias da Bexiga Urinária/patologia
16.
Zhong Yao Cai ; 39(2): 235-9, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-30080341

RESUMO

Objective: To study the effects of different plant density and harvest time on the yield and quality of Miao medicine Blumea balsamifera, in order to provide a theoretical basis for Good Agriculture Practice( GAP). Methods: Two factors trails were used to research the influence of plant density and harvest time on the yield and quality of Blumea balsamifera. The plant density were located at 50 cm × 90 cm,50 cm × 60 cm,50 cm × 30 cm and 30 cm × 30 cm, and the harvest time were set up at mid-October, mid-November and mid-December. The experiments were designed with randomized block design. Results: Yield and quality were both affected by the plant density and harvest time. Yield per unit area and volatile oil yield per unit area were increased significantly with the increasing of plant density. Yield per unit area and volatile oil yield per unit area were peaked at the plant density of 111 112 plants / hm~2 which could obtain high-yield at the mid-December, which were 1 546. 68 kg / hm~2 and 96. 6 L / hm~2,respectively. The content of total flavonoids were peaked at the plant density of 22 223 plants / hm~2 and 111 112 plants / hm~2,which were 2. 50 and 2. 53 mg/g,respectively. Harvest time had no significant effect on the flavonoids content. Conclusion: The suitable plant density of transplanted root tillers of Blumea balsamifera is 111 112 plants / hm~2 and the optimum harvest time is December.


Assuntos
Asteraceae , Agricultura , Flavonoides , Óleos Voláteis
17.
Zhong Yao Cai ; 39(3): 463-8, 2016 Mar.
Artigo em Zh | MEDLINE | ID: mdl-30088747

RESUMO

Objective: To investigate the main morphological characters and interrelationship of Blumea bdsamifera, and to provide the guidance for selection and breeding of Blumea balsamifera. Methods: 19 main morphological characters and their interrelationship were analyzed by using correlation analysis,multiple stepwise regression analysis and factor analysis. Results: Variation coefficients of the morphological characters were big in Blumea balsamifera. Correlation coefficients for morphological characters were significant( P <0. 05 or P < 0. 01). Using factor analysis,19 morphological characters were classified into six principal divisors. Ten morphological characters, including length / wide of leaf,trunk diameter, leaf number of second branch, leaf number of first branch, number of trunk leaf, weight of strong leaf, weight of young leaf,weight of old leaf, number of first branch, leaf number of whole plant, were the main factors which influenced the weight of whole plant leaf. Conclusion: The variation of every morphological character of Blumea balsamifera is abundant in different population, and a certain correlation is existed among morphological characters. The morphological characters, length / wide of leaf, trunk diameter, number of first branch, number and weight of leaf, are the main factors which influenced the weight of whole plant leaf.


Assuntos
Asteraceae , Folhas de Planta
18.
Tumour Biol ; 36(12): 9723-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26156799

RESUMO

Phospholipase Cε (PLCε) is a multifunctional enzyme implicated in inflammatory functions. There are limited data, however, on how PLCε can alter inflammatory cytokine by affecting downstream pathways. Recent studies suggest that inflammation is likely to have an important role in transitional cell carcinoma of bladder (TCCB) and cancer disease progression. Here, we showed that PLCε and p-STAT3 expression were both elevated in TCCB tissues compared to adjacent tissues, and the increase of PLCε level was associated with the increase of p-STAT3 level. Then, knockdown of PLCε using adenovirus-shPLCε significantly decreased inflammatory cytokine (IL-6, TNF-α, IL-1ß) expression and inflammation-associated gene (TLR4, MyD88, p-STAT3) expression. Furthermore, we demonstrated that PLCε knockdown blocked LPS-induced inflammatory cytokine and p-STAT3 expression. Additionally, we found that combined treatment of STAT3 inhibitor S3I-201 with adenovirus-shPLCε exhibited synergistic inhibitory effects on expression of p-STAT3. Our results suggested that STAT3 phosphorylation is involved in PLCε-mediated inflammatory cytokine release. Our research is of potential importance in drug development programs using PLCε as a therapeutic target for TCCB.


Assuntos
Carcinoma de Células de Transição/genética , Inflamação/genética , Fosfoinositídeo Fosfolipase C/genética , Fator de Transcrição STAT3/biossíntese , Neoplasias da Bexiga Urinária/genética , Carcinoma de Células de Transição/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Inflamação/patologia , Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Fosfoinositídeo Fosfolipase C/antagonistas & inibidores , Fosfoinositídeo Fosfolipase C/biossíntese , Fosforilação/genética , Fator de Transcrição STAT3/genética , Fator de Necrose Tumoral alfa/biossíntese , Neoplasias da Bexiga Urinária/patologia
19.
Zhongguo Zhong Yao Za Zhi ; 40(6): 1123-8, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-26226757

RESUMO

OBJECTIVE: To study the content of mineral elements and the principal components in Gastrodia elata. METHOD: Mineral elements were determined by ICP and the data was analyzed by SPSS. RESULT: K element has the highest content-and the average content was 15.31 g x kg(-1). The average content of N element was 8.99 g x kg(-1), followed by K element. The coefficient of variation of K and N was small, but the Mn was the biggest with 51.39%. The highly significant positive correlation was found among N, P and K . Three principal components were selected by principal components analysis to evaluate the quality of G. elata. P, B, N, K, Cu, Mn, Fe and Mg were the characteristic elements of G. elata. CONCLUSION: The content of K and N elements was higher and relatively stable. The variation of Mn content was biggest. The quality of G. elata in Guizhou and Yunnan was better from the perspective of mineral elements.


Assuntos
Medicamentos de Ervas Chinesas/análise , Gastrodia/química , Minerais/análise , Análise de Componente Principal
20.
Zhong Yao Cai ; 38(5): 883-8, 2015 May.
Artigo em Zh | MEDLINE | ID: mdl-26767278

RESUMO

OBJECTIVE: Combination of different planting direction and layer were set to choose the best technology of cultivation of Gastrodia elata f. elata. METHODS: To improve the yield and quality of Gastrodia elata f. elata, randomized block design experiments were carried out to investigate the yield and quality, and to analyze their economic effectiveness in bionic wild cultivation. RESULTS: Length, width, thickness and weight of southern direction's Gastrodia elata f. elata developed better than the northeast direction. The three planting layer levels on growth effect of Gastrodia elata f. elata was the 3rd layer > the 2nd layer > the 1st layer. In six treatments, combination of southern direction-the 3rd layer was the best technology of cultivation of Gastrodia elata f. elata, which had the best growth condition, the highest yield significantly higher than other treatments, and the best economic benefits. CONCLUSION: Southern direction associated with the 3rd layer is the best combination to planting Gastrodia elata f. elata in bionic wild cultivation. The planting ways not only improve the yield and quality, but also save land.


Assuntos
Agricultura/métodos , Gastrodia/crescimento & desenvolvimento , Plantas Medicinais/crescimento & desenvolvimento
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