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2.
Ecotoxicol Environ Saf ; 227: 112921, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34678626

RESUMO

In recent years, improving plants' resistance towards abiotic stresses with exogenous application of plant growth regulators and nutrients has emerged as a matter of great interest. The present study assessed the potential roles of kinetin (Kn, 0.2 mM) and calcium (Ca, 2 mM) in mitigating the salt (200 mM NaCl) induced inhibitory effects on seed germination and growth of choysum seedlings. The results indicated that NaCl stress significantly reduced the seed germination percentage (42.6%), germination potential (42.0%), germination index (52.1%), seedling vigor index (65.2%), and declined the fresh weight (43.8%), dry weight (52.2%), radicle length (37.2%), and plumule length (41.2%) of germinated seeds, compared to control treatment. The delayed germination and decrease in seedling growth were positively correlated with salinity-induced hormonal imbalance, ion toxicity, and oxidative stress. However, Kn and Ca pretreatment partially mitigated the adverse effects of NaCl stress, evident by early germination and enhanced seedling growth. Kn and Ca effectively increased the accumulation of proline, soluble protein, and soluble sugars, and upregulated the activities of superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase that significantly reduced the production of malondialdehyde, hydrogen peroxide, and superoxide anions in germinating seeds, thereby minimizing the NaCl-induced oxidative damages. Moreover, Kn and Ca pretreatment counteracted the NaCl-induced ionic toxicity by decreasing Na+ and increasing K+ contents and maintained a balanced Na+/K+ ratio in radicles and plumules of choysum seeds. Additionally, Kn and Ca under NaCl stress enhanced hormonal regulation by decreasing the ABA levels with a concomitant increase of GAs (especially GA4) levels and promoted early germination. Remarkably, the co-application of Kn and Ca was most effective by completely counteracting the inhibitory effects of NaCl and maintaining seed germination kinetics, seedling growth, and biochemical parameters almost similar to that in the stress-free control treatment. These results demonstrate that supplementation of Kn and Ca on choysum seeds is an effective chemical strategy regulating the various physiological and biochemical responses that would result in better germination and growth of seeds under stress conditions.


Assuntos
Brassica rapa , Plântula , Antioxidantes , Cálcio , Germinação , Cinetina/farmacologia , Sementes , Cloreto de Sódio
4.
J Exp Clin Cancer Res ; 40(1): 300, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556175

RESUMO

BACKGROUND: The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. METHODS: Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17ß-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. RESULTS: Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17ß-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. CONCLUSIONS: The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.

5.
J Cancer ; 12(14): 4240-4246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093824

RESUMO

Although tumor-derived exosomes play an important role in the process of metastasis, differences in exosomes secreted by the same cells at different stages or conditions have not been noticed by most of the relevant researchers. Here we developed a lung cancer model in nude mice, and the phenotype and inclusions of exosomes secreted by early and advanced tumors were analysed. The size distribution and surface topography of these two exosomes were not significantly different, but the expression of CD63 in early tumor exosome (E-exosome) was significantly lower than that in advanced tumor exosome (A-exosome). α-SMA expression on HELF cells treated with A-exosome was significantly higher than that treated with E-exosome. The ability of A-exosome to promote the migration of A549 cells was better than E-exosome. Furthermore, small RNA sequence showed that only 3 of the 171 detected-small RNAs were expressed simultaneously in both exosomes. These findings proved that there are significant differences in inclusions and functions between the early and late exosomes of the same tumor. The study highlights the importance of exosomes in cancer metastasis, and might suggest exosomes can be used as biomarkers and therapeutic targets for cancer metastasis.

7.
Chem Commun (Camb) ; 57(48): 5941-5944, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34018521

RESUMO

This work describes a single-stranded degradable modular grafting probe for analyzing microRNA-21. In the system, the exonuclease activity of phi29 polymerase restrains the SYBR Green I/ssDNA induced background. The palindrome activation caused remarkable target fluorescence. The detection limit was achieved as 0.26 fM, showing potential in biochemical analysis.


Assuntos
Benzotiazóis/química , DNA de Cadeia Simples/química , Diaminas/química , Exodesoxirribonucleases/química , MicroRNAs/análise , Quinolinas/química , Benzotiazóis/metabolismo , DNA de Cadeia Simples/metabolismo , Diaminas/metabolismo , Exodesoxirribonucleases/metabolismo , Fluorescência , Humanos , MicroRNAs/metabolismo , Técnicas de Amplificação de Ácido Nucleico , Quinolinas/metabolismo
8.
Anal Chim Acta ; 1150: 338221, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33583542

RESUMO

ANALYSIS: of molecular species is needed for applications in diagnosis of infections and genetic diseases. Herein, we demonstrate a target DNA-responsive ultrahigh fluorescence signal-on DNA amplification system via periodically programmed building and collapse of DNA networks. In this system, a pair of oligonucleotides of padlock probe (PP) and palindromic hairpin probe (PHP) are utilized. The presence of target DNA firstly hybridizes with PP, allowing the occurrence of rolling circle amplification (RCA) to produce RCA products with tandem repeats in abundance to bind and unfold numbers of PHPs. The conformational change of PHPs enables the building of DNA networks via the intermolecular palindrome pairing, but then makes the DNA networks collapsed via the palindrome-induced strand displacement polymerization. The displaced RCA products are dynamically reused to undergo periodically programmed multiple rounds of DNA network building and collapse. Depend on the bidirectional DNA assembly and disassembly, a strikingly amplified fluorescence can be collected to ultrasensitive and specific detection of target DNA. The practicability has been demonstrated by evaluating target-spiked human serum, saliva, and urine samples with acceptable recoveries and reproducibility. Therefore, this newly explored method opens a promising avenue for the detection of nucleic acids with low abundance in biochemical analysis and diseases diagnosis.


Assuntos
DNA , Técnicas de Amplificação de Ácido Nucleico , Humanos , Reprodutibilidade dos Testes , Espectrometria de Fluorescência
9.
Ecotoxicol Environ Saf ; 208: 111758, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396081

RESUMO

The cultivation of leafy vegetables on metal contaminated soil embodies a serious threat to yield and quality. In the present study, the potential role of exogenous jasmonic acid (JA; 0, 5, 10, and 20 µM) on mitigating chromium toxicity (Cr; 0, 150, and 300 µM) was investigated in choysum (Brassica parachinensis L.). With exposure to increasing Cr stress levels, a dose-dependent decline in growth, photosynthesis, and physio-biochemical attributes of choysum plants was observed. An increase in Cr levels also resulted in oxidative stress closely associated with higher lipoxygenase activity (LOX), hydrogen peroxide (H2O2) generation, lipid peroxidation (MDA), and methylglyoxal (MG) levels. Exogenous application of JA alleviated the Cr-induced phytotoxic effects on photosynthetic pigments, gas exchange parameters, and restored growth of choysum plants. While exposed to Cr stress, JA supplementation induced plant defense system via enhanced regulation of antioxidant enzymes, ascorbate and glutathione pool, and the glyoxalase system enzymes. The coordinated regulation of antioxidant and glyoxalase systems expressively suppressed the oxidative and carbonyl stress at both Cr stress levels. More importantly, JA restored the mineral nutrient contents, restricted Cr uptake, and accumulation in roots and shoots of choysum plants when compared to the only Cr-stressed plants. Overall, the application of JA2 treatment (10 µM JA) was more effective and counteracted the detrimental effects of 150 µM Cr stress by restoring the growth and physio-biochemical attributes to the level of control plants, while partially mitigated the detrimental effects of 300 µM Cr stress. Hence, JA application might be considered as an effective approach for minimizing Cr uptake and its detrimental effects in choysum plants grown on contaminated soils.


Assuntos
Antioxidantes/farmacologia , Brassica/fisiologia , Cromo/toxicidade , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Poluentes do Solo/toxicidade , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Brassica/efeitos dos fármacos , Brassica/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Oxirredução , Estresse Oxidativo/fisiologia , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo
10.
J Control Release ; 331: 404-415, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33485883

RESUMO

Each type of cancer has its own specific metastatic route developed by disseminating circulating tumor cells (CTCs) and related extracellular vesicles to the target organ, i.e., metastasis organotropism. Tumor-derived small extracellular vesicles (herein exosomes, EXO) play an important role in determining cancer organotropic metastases to pre-metastasis niches. We therefore hypothesized that drug-loaded EXO may mix well with their companion small extracellular vesicles to specifically target the aimed metastatic organ via organotropism. Here, we demonstrate that the circulating breast-cancer-derived EXO loaded with doxorubicin (EXO-DOX) can mingled with their original companion EXO and inhibit breast cancer metastasis to lungs. The CD47 on the EXO-DOX prevented EXO-DOX from immune attack and prolonged their circulation in blood. The tissue distribution ratio of EXO-DOX is identical to the ratio of their companion EXO due to the specific affinity of EXO to integrins in targeted tissues. Quantitative accumulation of EXO-DOX in the mouse lungs is proportional to the organotropism of the circulating breast cancer cells that disseminate from subcutaneously-implanted human breast cancer cells in mice. EXO-DOX inhibited angiogenesis and cancer cell proliferation, resulting in prevention of breast cancer metastasis to the lungs. This study opens a novel path to use Trojan small extracellular vesicles for specifically controlled release of active components by small extracellular vesicles organotropism mechanism to the targeted organ for disease chemoprevention.


Assuntos
Exossomos , Células Neoplásicas Circulantes , Preparações Farmacêuticas , Animais , Linhagem Celular Tumoral , Proliferação de Células , Doxorrubicina , Humanos , Camundongos
11.
Food Sci Nutr ; 8(11): 5811-5822, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33282233

RESUMO

In this study, the non-targeted large-scale plant metabolomics (UPLC-Q-Orbitrap-MS) was performed for the comparison of chemical profiling of the leaves, barks, flowers, peels, pulps, and seeds of Clausena lansium (Lour.) Skeels (called "wampee"). A total of 364 metabolites were identified, and 62 potential biomarkers were selected by the multivariate statistical analysis. Hierarchical cluster analysis suggested that the selected biomarkers were significant differential metabolites among various parts of wampee. Metabolic pathway analysis showed a significant enrichment of the "Flavone and flavonol synthesis" and "Isoquinoline alkaloid biosynthesis" pathway. This study provides important information for the isolation and identification of functional components from different tissues of wampee and the metabolic biosynthesis pathway elucidation in detail.

12.
Signal Transduct Target Ther ; 5(1): 238, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051439

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

14.
J Mater Chem B ; 8(37): 8671-8683, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32856668

RESUMO

Multifunctional nanomedical platforms have broad prospects in imaging-guided combination therapy in cancer precision medicine. In this work, metal-organic framework (MOF)-derived novel porous Fe3O4@C nanocomposites were developed as an intelligent cancer nanomedical platform for combined cancer therapy with MRI-guided magnetic-triggered hyperthermia and chemotherapy functions. The magnetic behavior, porous character and good surface modification endowed this smart nanoplatform with favorable biocompatibility, high-efficiency MRI imaging, magnetic-triggered on-demand DOX release function, and synergistic therapy of magnetic hyperthermia and chemotherapy, which proposed an all-in-one platform for cancer therapy. Additionally, in vivo animal experiments verified the significant suppression of malignant tumor growth with negligible side effects, which were attributed to the consecutive 13 day synergistic therapy of magnetic hyperthermia and chemotherapy in one. To be specific, Fe3O4@C-PVP@DOX significantly decreases the volume (2.5 to 0.44 of tumor volume ratio) and weight (0.49 g to 0.10 g) of tumors after magnetic-triggered hyperthermia and chemotherapy treatments. Moreover, no big difference of body weight and associated damage was observed among all major organs. Therefore, owing to its high-efficiency combined therapy of magnetic-triggered hyperthermia and chemotherapy, this smart nanoplatform holds great potential application in the precise treatments of clinical cancer.


Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Nanopartículas de Magnetita/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Nanocompostos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Terapia Combinada/métodos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Tratamento Farmacológico/métodos , Humanos , Hipertermia Induzida/métodos , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Masculino , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Nanocompostos/química , Nanocompostos/toxicidade , Porosidade , Povidona/química , Povidona/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
15.
BMC Oral Health ; 20(1): 184, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615964

RESUMO

BACKGROUND: Late diagnosis of a salivary fistula increases the risk of wound infection and scarring. The purpose of the present study was to identify a quantitative predictor of postoperative salivary fistula for cases treated with surgery. METHODS: Demographic, intraoperative and postoperative parameters for 57 cases that received surgery for benign parotid tumours were recorded from June 2017 to June 2018, of which 18 cases developed salivary fistulas. These data were analysed using univariate and binary logistic regression analyses as well as receiver operating curve analysis. RESULTS: Drain fluid amylase concentration was positively correlated with salivary fistula development (p <  0.001), with an odds ratio of 1.14 for a 1 KU/L increase in concentration and an optimal receiver operating curve cut-off value of 51,100 U/L for predicting salivary fistula development. Cases wherein the parotid-masseteric fascia remained intact were associated with a lower risk of salivary fistula development (p = 0.006). CONCLUSION: Drain fluid amylase concentration may be a valuable predictor of postoperative salivary fistula in cases with benign parotid tumours.


Assuntos
Amilases , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Complicações Pós-Operatórias , Fístula das Glândulas Salivares/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amilases/sangue , Drenagem , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Pancreaticoduodenectomia/efeitos adversos , Glândula Parótida/patologia , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto Jovem
16.
Am J Cancer Res ; 10(2): 454-472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195020

RESUMO

Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and related to cancer progression. The resistance to anti-EGFR therapy remains a major clinical problem in HNSCC. In this study, we found that TOLL-like receptor 4 (TLR4) was highly expressed in 50% of EGFR overexpressed HNSCC biopsies, which correlated to worse prognosis in patients. In HNSCC cell lines, activation of TLR4 reversed cetuximab-induced the inhibition of proliferation, migration and invasion. LPS induced of TLR4 signaling was potentiated under cetuximab treatment, showing increased activation of downstream NF-κB and MAPK pathways. Accordingly, cetuximab treatment also increased expression of TNF-α, COX2, and other molecules involved in TLR4 induced tumor inflammation. Mechanistically, we found inhibition of EGFR by cetuximab led to decreased phosphorylation of Src and sequentially Src-medicated activation of Cbl-b. This inhibited Cbl-b-mediated degradation of the key TLR4 adaptor protein MyD88 and activated TLR4 signaling. TLR4 or MyD88 overexpressed CAL27 and SCC4 cells grew faster and were more resistant to cetuximab and gefitinib both in vitro and in vivo. Out study delineates a crosstalk between EGFR and TLR4 pathways and identified TLR4 as a potential biomarker as well as a therapeutic target in overcoming the resistance to anti-EGFR therapy of HNSCC.

17.
Oncogene ; 39(13): 2741-2755, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32005977

RESUMO

The key molecules and underlying mechanisms of melanoma metastasis remain poorly understood. Using isobaric tag for relative and absolute quantitation (iTRAQ) proteomic screening, probing of patients' samples, functional verification, and mechanistic validation, we identified the important role of the WD repeat-containing protein 74 (WDR74) in melanoma progression and metastasis. Through gain- and loss-of-function approaches, WDR74 was found to promote cell proliferation, apoptosis resistance, and aggressive behavior in vitro. Moreover, WDR74 contributed to melanoma growth and metastasis in vivo. Mechanistically, WDR74 modulates RPL5 protein levels and consequently regulates MDM2 and insulates the ubiquitination degradation of p53 by MDM2. Our study is the first to reveal the oncogenic role of WDR74 in melanoma progression and the regulatory effect of WDR74 on the RPL5-MDM2-p53 pathway. Collectively, WDR74 can serve as a candidate target for the prevention and treatment of melanoma in the clinic.


Assuntos
Carcinogênese/patologia , Melanoma/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Cutâneas/patologia , Animais , Apoptose/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Técnicas de Inativação de Genes , Humanos , Melanoma/genética , Camundongos , Fosforilação , Proteólise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Ribossômicas/metabolismo , Transdução de Sinais/genética , Pele/patologia , Neoplasias Cutâneas/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação/genética , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Chem Commun (Camb) ; 56(11): 1681-1684, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31939961

RESUMO

A functionalized dumbbell probe (FDP) based amplification method, termed as a cascading exponential amplification DNA machine (CEA-DNA machine), has been developed to autonomously accumulate single G-quadruplexes (SGQs) and twin-G-quadruplexes (TGQs) for robust fluorescence signal-on probing of miRNA-21.


Assuntos
DNA/química , MicroRNAs/sangue , Técnicas de Amplificação de Ácido Nucleico/métodos , Espectrometria de Fluorescência/métodos , Benzotiazóis/química , Técnicas Biossensoriais/métodos , Linhagem Celular Tumoral , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Corantes Fluorescentes/química , Quadruplex G , Humanos , Sequências Repetidas Invertidas , Limite de Detecção , MicroRNAs/genética , Hibridização de Ácido Nucleico
19.
Molecules ; 25(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906347

RESUMO

In this study, the phytochemical profiles, total and cellular antioxidant activities of five different Chinese chestnut (Castanea mollissima BL.) cultivars were analyzed. Phenolics, flavonoids as well as phytochemical compounds in five cultivars of chestnut kernels were determined. Results showed that the free forms played a dominant role in total phenolics, flavonoids and antioxidant activities of all five cultivars of chestnut kernels. The cultivar 'Fyou' showed the highest total and free phenolic contents, 'Heguoyihao' showed the highest total and free flavonoids contents, and 'Chushuhong' showed the highest total and cellular antioxidant activities. Eight phenolic compounds were detected, and chlorogenic acid, gallic acid, and quercetin were shown as three predominant components in all five cultivars. These results provide valuable information which may be a guidance for selection of good chestnut variety to be used as functional food.


Assuntos
Antioxidantes/análise , Antioxidantes/farmacologia , Fagaceae/química , Flavonoides/análise , Fenóis/análise , Compostos Fitoquímicos/análise , Antioxidantes/química , Flavonoides/química , Frutas/química , Células Hep G2 , Humanos , Fenóis/química , Compostos Fitoquímicos/química , Extratos Vegetais/química
20.
Nat Commun ; 11(1): 243, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913267

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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