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1.
Chembiochem ; : e202400346, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775416

RESUMO

Multi-enzyme cascade catalysis has become an important technique for chemical reactions used in manufacturing and scientific study. In this research, we designed a four-enzyme integrated catalyst and used it to catalyse the racemization reaction of cyclic chiral amines, where monoamine oxidase (MAO) catalyses the selective oxidation of 1-methyl-1,2,3,4-tetrahydroisoquinoline (MTQ), imine reductase (IRED) catalyses the selective reduction of 1-methyl-3,4-dihydroisoquinoline (MDQ), formate dehydrogenase (FDH) is used for the cyclic regeneration of cofactors, and catalase (CAT) is used for decomposition of oxidative reactions. The four enzymes were immobilized via polydopamine (PDA)-encapsulated dendritic organosilica nanoparticles (DONs) as carriers, resulting in the amphiphilic core-shell catalysts. The hydrophilic PDA shell ensures the dispersion of the catalyst in water, and the hydrophobic DON core creates a microenvironment with the spatial confinement effect of the organic substrate and the preconcentration effect to enhance the stability of the enzymes and the catalytic efficiency. The core-shell structure improves the stability and reusability of the catalyst and rationally arranges the position of different enzymes according to the reaction sequence to improve the cascade catalytic performance and cofactor recovery efficiency.

2.
J Sci Food Agric ; 103(15): 7905-7913, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37490703

RESUMO

BACKGROUND: Electrolyzed water (EW) is recognized as an effective way to control and reduce pathogens in vegetables. However, the disinfection efficacy of EW alone is limited. In this work, the bactericidal activity and biofilm removal capability of EW, generated by adding NaCl to a portable EW generator, were investigated with special reference to Listeria monocytogenes. Furthermore, the impact of EW in combination with dimethyl dicarbonate (DMDC) in reducing the microbial load and improving the overall quality of lettuce during refrigerated storage was evaluated. RESULTS: EW with 0.3% NaCl (SEW) had the highest bactericidal activity against L. monocytogenes. The pathogen treated with SEW exhibited lower superoxide dismutase activity and more leakage of proteins and nucleic acids than in the case of EW. Furthermore, the use of SEW resulted in changes in the cell permeability and morphology of L. monocytogenes. A decrease in adhesion and collapse of the biofilm architecture were also observed, indicating that SEW was more effective for inactivating L. monocytogenes cells compared to EW. For untreated lettuce, the populations of the total plate count and inoculated L. monocytogenes decreased by 2.47 and 2.35 log CFU g-1 , respectively, after the combined SEW/DMDC treatment for 3 min. The use of SEW alone or combined with DMDC did not negatively impact the lettuce color values, titratable acid, ascorbic acid and soluble solids compared to the control group. CONCLUSION: SEW in combination with DMDC can be used as a novel and potentially effective disinfection strategy for ensuring the safety of vegetable consumption. © 2023 Society of Chemical Industry.


Assuntos
Desinfetantes , Listeria monocytogenes , Lactuca , Água/farmacologia , Cloreto de Sódio/farmacologia , Desinfetantes/farmacologia , Microbiologia de Alimentos , Eletrólise , Contagem de Colônia Microbiana , Verduras
3.
J Cell Mol Med ; 24(18): 10935-10945, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32767729

RESUMO

The activation of liver macrophages is closely related to liver injury after HBV infection. Our previous results demonstrated that HBeAg played a key role in inducing macrophage activation. As we all know, miRNAs are involved in the regulation of multiple immune cell functions. Meanwhile, we have shown that miR-155 positively regulates HBeAg-induced macrophage activation and accelerates liver injury. Subsequently, based on our previous miRNA sequencing results, we further evaluated the role of miR-212-3p called 'neurimmiR' in HBeAg-induced macrophages in this study. First, miR-212-3p expression was significantly elevated in HBeAg-treated macrophages. Meanwhile, we found up-regulation of miR-212-3p significantly decreased the production of cytokines, whereas knockdown of miR-212-3p held the opposite effect by gains and losses of function. Mechanically, although MAPK signal pathway, including ERK, JNK and p38, was activated in HBeAg-induced macrophages, only ERK promoted the expression of miR-212-3p via transcription factor CREB, which was able to bind to the promoter of miR-212-3p verified by ChIP assay. Moreover, we further indicated that up-regulated miR-212-3p inhibited HBeAg-induced inflammatory cytokine production through targeting MAPK1. In conclusion, miR-212-3p was augmented in HBeAg-stimulated macrophages via ERK/CREB signal pathway and the elevated miR-212-3p suppressed inflammatory cytokine production induced by HBeAg through targeting MAPK1.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Antígenos E da Hepatite B/imunologia , Sistema de Sinalização das MAP Quinases/fisiologia , Ativação de Macrófagos/genética , MicroRNAs/genética , Animais , Imunoprecipitação da Cromatina , Citocinas/metabolismo , Retroalimentação Fisiológica , Regulação da Expressão Gênica , Humanos , Inflamação , Camundongos , MicroRNAs/biossíntese , Monócitos/citologia , Monócitos/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Ligação Proteica , Células RAW 264.7 , Células THP-1 , Células U937
4.
J Neurooncol ; 111(3): 237-44, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23232806

RESUMO

Human chorionic gonadotropin ß (hCGß) promotes tumorigenesis in a variety of tumors including glioblastoma, breast and prostate cancer cells, etc. However, the involved mechanisms remain elusive. Distinct from the other tumors, glioblastoma is a highly invasive brain tumor; invasion causes high recurrence and mortality. Characterization of hCGß signaling is to determine therapeutic targets to inhibit invasion and lower recurrence. Through both a stable cell line over-expressing hCGß and hCGß standards, we tested hCGß signaling, migration and invasion in human glioblastoma U87MG cells. ELISA showed that hCGß secreted into culture medium at an amount of 237.8 ± 7.8 ng/10(7) cells in hCGß transfected stable cells after the cells were grown for 24 h. Through Western blot and Gelatin zymography, we found that hCGß standards phosphorylated ERK1/2 and upregulated MMP-2 expression in dose- and time-dependent manners. Meanwhile, overexpressed hCGß phosphorylated ERK1/2, and upregulated MMP-2 expression and activity, whereas ERK1/2 blocker PD98059 (25 µM) significantly decreased both ERK1/2 and MMP-2 expression and activity. In addition, in the same conditions as the signaling test, hCGß promoted cell migration and invasion, whereas the PD98059 diminished these effects. These findings demonstrated that hCGß phosphorylated ERK1/2 upregulating MMP-2 expression and activity leading to cell migration and invasion, suggesting that hCGß, ERK1/2 and MMP-2 are the potential targets to inhibit glioblastoma invasion.


Assuntos
Movimento Celular/efeitos dos fármacos , Gonadotropina Coriônica Humana Subunidade beta/farmacologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Metaloproteinase 2 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Gonadotropina Coriônica Humana Subunidade beta/genética , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/patologia , Humanos , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transfecção
5.
Plants (Basel) ; 12(18)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37765501

RESUMO

Drought stress is one of the major causes of crop losses. The WRKY families play important roles in the regulation of many plant processes, including drought stress response. However, the function of individual WRKY genes in plants is still under investigation. Here, we identified a new member of the WRKY families, OsWRKY97, and analyzed its role in stress resistance by using a series of transgenic plant lines. OsWRKY97 positively regulates drought tolerance in rice. OsWRKY97 was expressed in all examined tissues and could be induced by various abiotic stresses and abscisic acid (ABA). OsWRKY97-GFP was localized to the nucleus. Various abiotic stress-related cis-acting elements were observed in the promoters of OsWRKY97. The results of OsWRKY97-overexpressing plant analyses revealed that OsWRKY97 plays a positive role in drought stress tolerance. In addition, physiological analyses revealed that OsWRKY97 improves drought stress tolerance by improving the osmotic adjustment ability, oxidative stress tolerance, and water retention capacity of the plant. Furthermore, OsWRKY97-overexpressing plants also showed higher sensitivity to exogenous ABA compared with that of wild-type rice (WT). Overexpression of OsWRKY97 also affected the transcript levels of ABA-responsive genes and the accumulation of ABA. These results indicate that OsWRKY97 plays a crucial role in the response to drought stress and may possess high potential value in improving drought tolerance in rice.

6.
Front Neurol ; 13: 963334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237612

RESUMO

Introduction: Cognitive impairment is the main clinical feature after traumatic brain injury (TBI) and is usually characterized by attention deficits, memory loss, and decreased executive function. Vagus nerve stimulation (VNS) has been reported to show potential improvement in the cognition level after traumatic brain injury in clinical and preclinical studies. However, this topic has not yet been systematically reviewed in published literature. In this study, we present a systematic review and meta-analysis of the effects of VNS on cognitive function in animal models of TBI and their underlying mechanisms. Methods: We performed a literature search on PubMed, PsycINFO, Web of Science, Embase, Scopus, and Cochrane Library from inception to December 2021 to identify studies describing the effects of VNS on animal models of TBI. Results: Overall, nine studies were identified in animal models (36 mice, 268 rats, and 27 rabbits). An analysis of these studies showed that VNS can improve the performance of TBI animals in behavioral tests (beam walk test: SMD: 4.95; 95% confidence interval [CI]: 3.66, 6.23; p < 0.00001) and locomotor placing tests (SMD: -2.39; 95% CI: -4.07, -0.71; p = 0.005), whereas it reduced brain edema (SMD: -1.58; 95% CI: -2.85, -0.31; p = 0. 01) and decrease TNF-α (SMD: -3.49; 95% CI: -5.78, -1.2; p = 0.003) and IL-1ß (SMD: -2.84; 95% CI: -3.96, -1.71; p < 0.00001) expression level in the brain tissue. However, the checklist for SYRCLE showed a moderate risk of bias (quality score between 30% and 60%), mainly because of the lack of sample size calculation, random assignment, and blinded assessment. Conclusion: The present review showed that VNS can effectively promote cognitive impairment and neuropathology in animal models of TBI. We hope that the results of this systematic review can be applied to improve the methodological quality of animal experiments on TBI, which will provide more important and conclusive evidence on the clinical value of VNS. To further confirm these results, there is a need for high-quality TBI animal studies with sufficient sample size and a more comprehensive outcome evaluation. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290797, identifier: CRD42021290797.

7.
Dis Markers ; 2022: 9516808, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36583064

RESUMO

Background: Glioma is the most prevalent malignant brain tumor in adult humans, and glioblastoma (GBM) is the most malignant type. The actin-binding LIM 1 (ABLIM1) protein can modulate actin polymerization, which is essential for the cell proliferation and migration. We aim to investigate ABLIM1 expression, function, and clinical significance in GBM. Methods: The ABLIM1 mRNA level was extracted from the TCGA and GTEx online databases. The ABLIM1 protein expression level was explored using immunohistochemistry staining in a GBM cohort enrolled in our hospital (n = 104). The patient survival and prognostic factors were determined using the Kaplan-Meier method and multivariate Cox hazard proportional analysis, respectively. Two human GBM cell lines, U87 and U251 cells, were utilized for ABLIM1 overexpression and cell proliferation analyses. A subcutaneous xenograft model was generated using nude mice to validate the tumor-related effect of ABLIM1 in vivo. Results: ABLIM1 exhibited a significantly lower mRNA level in GBM than in other glioma or normal brain tissues. Higher ABLIM1 protein level was correlated with smaller GBM tumor size and better cancer-specific survival (CSS). Multivariate analysis identified ABLIM1 as a novel independent prognostic factor for GBM prognosis. ABLIM1 overexpression significantly inhibits U87 and U251 cell proliferation and colony formation. Consistently, ABLIM1 exerted tumor-suppressing functions in mice models. Conclusion: ABLIM1 plays antitumor roles in GBM progression and could be served as a novel biomarker to help predict GBM prognosis.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Proteínas com Domínio LIM , Proteínas dos Microfilamentos , Adulto , Animais , Humanos , Camundongos , Actinas/genética , Actinas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Glioma/genética , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Camundongos Nus , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Prognóstico , RNA Mensageiro/genética
8.
Front Immunol ; 13: 1005925, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311722

RESUMO

Streptococcus equi subsp. zooepidemicus (S. zooepidemicus, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. Gasdermin D (GSDMD) is involved in cytokine release and cell death, indicating an important role in controlling the microbial infection. This study investigated the protective role of GSDMD in mice infected with SEZ and examined the role of GSDMD in peritoneal macrophages in the infection. GSDMD-deficient mice were more susceptible to intraperitoneal infection with SEZ, and the white pulp structure of the spleen was seriously damaged in GSDMD-deficient mice. Although the increased proportion of macrophages did not depend on GSDMD in both spleen and peritoneal lavage fluid (PLF), deficiency of GSDMD caused the minor release of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) during the infection in vivo. In vitro, SEZ infection induced more release of IL-1ß, IL-18, and lactate dehydrogenase (LDH) in wild-type macrophages than in GSDMD-deficient macrophages. Finally, we demonstrated that pore formation and pyroptosis of macrophages depended on GSDMD. Our findings highlight the host defense mechanisms of GSDMD against SEZ infection, providing a potential therapeutic target in SEZ infection.


Assuntos
Piroptose , Streptococcus equi , Camundongos , Animais , Piroptose/fisiologia , Proteínas de Ligação a Fosfato/metabolismo , Streptococcus equi/metabolismo , Interleucina-18/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo
9.
Nanomaterials (Basel) ; 11(12)2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34947573

RESUMO

Li2ZrO3-coated and Al-doped micro-sized monocrystalline LiMn2O4 powder is synthesized through solid-state reaction, and the electrochemical performance is investigated as cathode materials for lithium-ion batteries. It is found that Li2ZrO3-coated LiAl0.06Mn1.94O4 delivers a discharge capacity of 110.90 mAhg-1 with 94% capacity retention after 200 cycles at room temperature and a discharge capacity of 104.4 mAhg-1 with a capacity retention of 87.8% after 100 cycles at 55 °C. Moreover, Li2ZrO3-coated LiAl0.06Mn1.94O4 could retain 87.5% of its initial capacity at 5C rate. This superior cycling and rate performance can be greatly contributed to the synergistic effect of Al-doping and Li2ZrO3-coating.

10.
PLoS One ; 16(8): e0256807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34449822

RESUMO

Rice blast, caused by the fungus Magnaporthe oryzae, is one of the three major diseases affecting rice production and quality; it reduces rice grain yield by nearly 30%. In the early stage of this study, a strain of Bacillus velezensis with strong inhibition of M. oryzae was isolated and named ZW10. In vitro assays indicated prolonged germination time of conidia of M. oryzae treated with the antifungal substances of ZW10, 78% of the conidia could not form appressorium, and the conidial tubes expanded to form vacuolar structure and then shrank. The results of FDA-PI composite dyes showed that the antifungal substances of ZW10 inhibited the normal activity of M. oryzae hyphae that were rarely able to infect the epidermal cells of rice leaf sheath in vivo tests. In addition, rice treated with the antifungal substances of ZW10 showed a variety of defense responses, including activation of defense-related enzymes, increased expression of the salicylic acid pathway genes, and accumulation of hydrogen peroxide (H2O2), which might function directly or indirectly in resistance to pathogen attack. The field experiment with rice blast infection in different periods showed that the antifungal substances of ZW10 had the same control effect as carbendazim. The significant biological control activity of ZW10 and its capacity to stimulate host defenses suggest that this B. velezensis strain has the potential to be developed into a biopesticide for the biocontrol of rice blast.


Assuntos
Ascomicetos/genética , Bacillus/genética , Oryza/crescimento & desenvolvimento , Doenças das Plantas/genética , Antifúngicos/metabolismo , Ascomicetos/patogenicidade , Bacillus/metabolismo , Agentes de Controle Biológico/metabolismo , Magnaporthe/genética , Magnaporthe/patogenicidade , Oryza/genética , Oryza/microbiologia , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Folhas de Planta/microbiologia , Esporos Fúngicos/genética , Esporos Fúngicos/patogenicidade
11.
Onco Targets Ther ; 13: 3677-3687, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431518

RESUMO

INTRODUCTION: The secretory carrier-associated membrane protein 3 (SCAMP3) is a component of post-Golgi membranes, functions as a protein carrier and is critical for subcellular protein transportation. Limited studies revealed an elevated expression of SCAMP3 in breast cancer and hepatocellular carcinoma; however, its role in glioma remains unknown. The aim of our study is to investigate the expression pattern and functional mechanisms of SCAMP3 in glioma. METHODS: mRNA and protein levels of SCAMP3 were examined in glioma tissues together with nontumorous brain tissues by using quantitative real-time-PCR and immunohistochemistry staining. The prognostic role of SCAMP3 in glioma was evaluated through univariate and multivariate analyses. In vitro and in vivo assays were conducted to explore the underlying mechanisms of SCAMP3-induced glioma progression. RESULTS: The expression level of SCAMP3 was higher in glioma tissues than that in normal brain tissues. High protein level of SCAMP3 was correlated with larger tumor size and advanced WHO grade. Glioma patients with high-SCAMP3 level had worse overall survival. In addition, SCAMP3 was defined as an independent risk factor of glioma prognosis. Cellular and xenograft studies revealed that SCAMP3 promotes glioma proliferation possibly through enhancing EGFR and mTORC1 signaling. DISCUSSION: Our studies revealed that high-SCAMP3 expression level was closely related to the unfavorable clinical features and poor prognosis of glioma patients. SCAMP3 may serve as an invaluable prognostic indicator and novel therapeutic target for glioma treatment.

12.
Front Neurol ; 11: 178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292385

RESUMO

Background: Mild cognitive impairment (MCI) is common among elderly people. So far, effective treatment that can stabilize or reverse the cognitive decline associated with MCI is lacking. Recent studies suggest that playing mahjong may improve attention and memory in elderly people. However, its effect on executive function remains unknown. Methods: 56 elderly people (74.3 ± 4.3 years of age) with MCI from the First Social Welfare the First Nursing Home of Nanchong were randomized into mahjong and control groups (N = 28, each group). Subjects in the mahjong group played mahjong three times a week for 12 weeks, while people in the control group assumed normal daily activity. Executive function was evaluated using the Montreal Cognitive Assessment-Beijing (MoCA-B), the Shape Trail Test (STT), and the Functional Activities Questionnaire (FAQ) before the study and then at 6 and 12 weeks after mahjong administration. Results: There were no baseline differences in MoCA-B, STT, and FAQ scoring between the two groups. The MoCA-B, STT, and FAQ scores, however, improved significantly in the mahjong group but not in the control group after the 12-week mahjong administration. Significant correlations were also found between STT and FAQ scores. Conclusions: Playing Mahjong for 12 weeks improved the executive function of elderly people with MCI. Because Mahjong is a simple, low-cost entertainment activity, it could be widely applied to slow down or reverse the progression of cognitive decline in people with MCI, including those with traumatic brain injury.

13.
ACS Appl Mater Interfaces ; 12(12): 13836-13841, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32159335

RESUMO

Li7La3Zr2O12 (LLZO)-based ceramics are well-known as the most promising solid electrolytes for all-solid-state lithium metal batteries. However, its practical application has been significantly hindered by high Li/LLZO interfacial impedance as a result of poor interfacial contact. To solve these issues, in this work, the ZnO layer was magnetron sputter-deposited on Li6.55La2.95Ca0.05Zr1.5Ta0.5O12 (LLCZTO) pellets. It was found that by introducing a 200 nm thick ZnO layer, the interfacial area specific resistance was sharply reduced to as low as 1% that of pristine LLCZTO; meanwhile, Li plating/stripping performance was improved significantly with a long life span of 320 h and a low polarization potential of 0.1 V, whereas a thicker ZnO layer of 600 nm can only improve the interface contact to a very limited extent because of the accumulated volume expansion induced by the in situ transformation of ZnO to the Li-Zn alloy, demonstrating the thickness-dependent beneficial effect of the ZnO layer on improving the Li/LLCZTO interfacial contact and therefore reducing the interfacial resistance. Accordingly, the evolution of the interfacial contact mode and the Li+ migration mechanism during the Li plating/stripping process without or with ZnO layers of different thicknesses were discussed in detail.

14.
RSC Adv ; 9(6): 3436-3442, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35518971

RESUMO

In this work, to improve the cyclability and high-temperature performance of cubic spinel LiMn2O4 (LMO) as cathode materials, Nb5+-doped LiMn2O4 powders coated and uncoated with Al2O3 and/or B2O3 were synthesized via the modified solid-state reaction method. It was found that Nb5+-doped and B2O3 + Al2O3-coated LMO powders comprising 5 µm granular agglomerated fine primary particles smaller than 350 nm in diameter exhibited superior electrochemical properties with initial discharge capacity of 101.68 mA h g-1; we also observed capacity retention of 96.31% after 300 cycles at room temperature (RT) and that of 98% after 50 cycles at 55 °C and 1C rate.

15.
Springerplus ; 5: 235, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27026929

RESUMO

In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities. In the present study, the viability inhibition effects of SFN in U251MG glioblastoma cells were analyzed by MTS. Morphology changes were observed by microscope. Apoptotic effects of SFN were evaluated by annexin V binding capacity with flow cytometric analysis. Invasion inhibition effects of SFN were tested by the invasion assay. The molecular mechanisms of apoptotic effects and invasion inhibition effects of SFN were detected by western blot and gelatin zymography. The results indicated that SFN has potent apoptotic effects and invasion inhibition effects against U251MG glioblastoma cells. These effects are both dose dependent. Taken together, SFN possessed apoptotic activity on U251MG cells indicated by increased annexin V-binding capacity, Bad, Bax, cytochrome C expression, and decreased Bcl-2 and survivin expressions. SFN inhibited invasion in U251MG cells via upregulation of E-cadherin and downregulation of MMP-2, MMP-9 and Galectin-3.

16.
Oncol Rep ; 34(3): 1565-72, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26134113

RESUMO

Advanced prostate cancer has highly invasive potential, which may lead to metastasis associated with poor prognosis. Sulforaphane (SFN), abundant in cruciferous vegetables, exhibited effective resistance to carcinogenesis in a variety of tumors. The aim of the present study was to investigate whether SFN inhibited invasion in human prostate cancer cells via sustained activation of ERK1/2 and downstream signaling by an invasion assay, gelatin zymography and western blot analysis. The results showed that SFN inhibited invasion and we characterized the underlying mechanisms in human DU145 prostate cancer cells. SFN (15 µM) changed cell morphology leading to short­cell pseudopodia which may suppress tumor migration and invasion. The Transwell assay showed that SFN phosphorylated ERK1/2 in a dose- and time-dependent manner and significantly inhibited cell invasion, while the effect was reduced by the ERK1/2 blocker PD98059 (25 µM). Furthermore, these effects contributed to the upregulation of E-cadherin and the downregulation of CD44v6 and were eradicated by PD98059. Western blot analysis and gelatin zymography showed that SFN decreased the expression and activity of MMP-2. Thus, SFN inhibited invasion by activating ERK1/2 to upregulate E-cadherin and downregulate CD44v6, thereby reducing MMP-2 expression and activity. E-cadherin is an invasion inhibitor, while CD44v6 and MMP-2 are invasion promoters. Therefore, SFN is a prospective therapeutic agent that may be used to prevent invasion in prostate cancer.


Assuntos
Caderinas/biossíntese , Receptores de Hialuronatos/biossíntese , Isotiocianatos/administração & dosagem , Metaloproteinase 2 da Matriz/biossíntese , Neoplasias da Próstata/tratamento farmacológico , Caderinas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinase 2 da Matriz/genética , Invasividade Neoplásica/genética , Fosforilação , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Sulfóxidos
17.
PLoS One ; 9(2): e90520, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24587385

RESUMO

BACKGROUND: Glioblastoma has highly invasive potential, which might result in poor prognosis and therapeutic failure. Hence, the key we study is to find effective therapies to repress migration and invasion. Sulforaphane (SFN) was demonstrated to inhibit cell growth in a variety of tumors. Here, we will further investigate whether SFN inhibits migration and invasion and find the possible mechanisms in human glioblastoma U87MG and U373MG cells. METHODS: First, the optimal time and dose of SFN for migration and invasion study were determined via cell viability and cell morphological assay. Further, scratch assay and transwell invasion assay were employed to investigate the effect of SFN on migration and invasion. Meanwhile, Western blots were used to detect the molecular linkage among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2 (MMP-2) and CD44v6. Furthermore, Gelatin zymography was performed to detect the inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 µM) was integrated to find the link between activated ERK1/2 and invasion, MMP-2 and CD44v6. RESULTS: The results showed that SFN (20 µM) remarkably reduced the formation of cell pseudopodia, indicating that SFN might inhibit cell motility. As expected, scratch assay and transwell invasion assay showed that SFN inhibited glioblastoma cell migration and invasion. Western blot and Gelatin zymography showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to the downregulated MMP-2 expression and activity, and the upregulated CD44v6 expression. These molecular interactions resulted in the inhibition of cell invasion. CONCLUSIONS: SFN inhibited migration and invasion processes. Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its activity and upregulated CD44v6. SFN might be a potential therapeutic agent by activating ERK1/2 signaling against human glioblastoma.


Assuntos
Movimento Celular/efeitos dos fármacos , Isotiocianatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Anticarcinógenos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Flavonoides/farmacologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Receptores de Hialuronatos/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Sulfóxidos , Regulação para Cima/efeitos dos fármacos
18.
PLoS One ; 8(2): e54592, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23424616

RESUMO

We previously demonstrated that human chorionic gonadotropin ß (hCGß) induced migration and invasion in human prostate cancer cells. However, the involved molecular mechanisms are unclear. Here, we established a stable prostate cancer cell line overexpressing hCGß and tested hCGß-triggered signaling pathways causing cell migration and invasion. ELISA showed that the hCGß amount secreted into medium increased with culture time after the hCGß-transfected cells were incubated for 3, 6, 9, 12 and 24 h. More, hCGß standards promoted MAPK (ERK1/2) phosphorylation and increased MMP-2 expression and activity in both dose- and time-dependent manners in hCGß non-transfected cells. In addition, hCGß promoted ERK1/2 phosphorylation and increased MMP-2 expression and activity significantly in hCGß transfected DU145 cells. Whereas ERK1/2 blocker PD98059 (25 µM) significantly downregulated phosphorylated ERK1/2 and MMP-2. Particularly, hCGß promoted cell migration and invasion, yet the PD98059 diminished the hCGß-induced cell motility under those conditions. These results indicated that hCGß induced cell motility via promoting ERK1/2 phosphorylation and MMP-2 upregulation in human prostate cancer DU145 cells.


Assuntos
Movimento Celular , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Gonadotropina Coriônica Humana Subunidade beta/genética , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Fosforilação , Transdução de Sinais
19.
Mater Sci Eng C Mater Biol Appl ; 32(6): 1664-8, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24364974

RESUMO

In order to develop new ß-type Ti-based biochemical materials, a series of Ti-10Mo-1.25Si-xZr (x=4-13) alloys were designed and prepared using vacuum arc melting method. Phase analysis and microstructural observation showed that all the as cast samples consisted of equiaxed ß-Ti phase. With the increase of Zr content, the structure of grain boundary changed from semi-continuous network to denser granular, and the microstructure was refined. The solid solution effect of the ß-phase stabilization elements (i.e. Mo, Zr and Si) predominantly determined the mechanical properties. These ß-type Ti-10Mo-1.25Si-xZr biomaterials exhibited a good combination of high compressive strength, high yield stress, good plasticity, as well as rather low Young's modulus (in the range of 23.086 GPa-32.623 GPa), which may offer potential advantages in the applications in hard tissue replacements (HTRs).


Assuntos
Materiais Biocompatíveis/química , Alicerces Teciduais/química , Titânio/química , Ligas/química , Força Compressiva , Módulo de Elasticidade , Dureza , Teste de Materiais/métodos , Engenharia Tecidual/métodos
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