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1.
Artigo em Inglês | MEDLINE | ID: mdl-38330562

RESUMO

Objective: This study investigates the efficacy of tangerine peel lemon glycerin extract oral spray in improving oral mucosal barrier, reducing microinflammation, and addressing malnutrition in maintenance dialysis (MHD) patients. Methods: Tangerine peel and dry lemon underwent glycerin extraction. From January 2021 to June 2022, 72 MHD patients with thirst were prospectively chosen at Sinopharm Gezhouba Central Hospital. Randomization divided them into an observation group (n=36) and a control group (n=36). Both received routine maintenance dialysis and chronic kidney disease management. Oral conditions were assessed using OHIP-14, a homemade visual thirst score scale, SFR, sAA, and saliva pH. Microinflammatory indexes (CRP, TNF-α, IL-6) and nutritional status indicators (Alb, PA, Hb) were measured. The observation group used 1ml of tangerine peel lemon glycerin extract with a pH value of 5.9~6.1 q6h, while the control group used 1ml of purified water q6h. Results: After 3 months, the observation group showed significant improvement in OHIP-14 and visual thirst score scale (P < .01). Saliva pH, CRP, TNF-α, and IL-6 levels decreased, and SAA activity, SFR, Alb, PA, and Hb levels increased significantly in the observation group compared to the control group (P < .01). Conclusions: Tangerine peel lemon glycerin spray demonstrates promise in improving the oral mucosal barrier, exhibiting antibacterial and anti-inflammatory properties that mitigate microinflammation and malnutrition. This finding suggests a connection between oral health, systemic pathology, psychological state, and social adaptability.

2.
Biol Sport ; 41(3): 243-266, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952914

RESUMO

This systematic review aims to provide a summary of the results from individual studies that specifically focused on overweight or obese populations, regardless of age or sex. The goal is to determine the effects of structured recreational team sports interventions (TSG) on metabolic health, body composition and physical fitness parameters when compared to passive or active control groups. This study adhered to the PRISMA guidelines for reporting a systematic review. A thorough examination of relevant literature was conducted on November 06, 2023, using three prominent databases: PubMed, Scopus, and the Web of Science. Inclusion criteria considered overweight (e.g., BMI 25.0-29.9 kg/m2) and obese (e.g., BMI > 30 kg/m2) populations exposed to training interventions using recreational team sports, while the comparator group consisted of the same populations not exposed to exercise (passive controls) or exposed to alternative training methods. The primary outcomes of interest were metabolic health parameters (glucose, waist circumference, blood pressure, cholesterol, triglycerides), body composition (e.g., fat mass, lean mass), as well as physical fitness parameters (e.g., aerobic fitness, muscular fitness). Only studies with two- or multi-arm designs, whether randomized or not, were eligible for inclusion. The PEDro scale was used to assess the methodological bias of the included studies. Out of the initial 275 titles retrieved, we deemed ten eligible for our study. In terms of body composition, TSG demonstrated a significant decrease in body mass index across three studies (-2.3 to -5.1%) and a significant reduction in waist circumference in four studies (-4.6% to -8.4%). Regarding blood pressure, TSG exhibited a significant decrease in systolic blood pressure in two studies (-3.9% to -8.3%), while diastolic blood pressure showed a significant decrease in only one study (-7.3%). Cholesterol levels saw a significant decrease in TSG in three studies (-7.0% to -9.7%), and triglyceride levels showed a significant reduction in four studies (-16.4% to -20.1%). In terms of aerobic fitness, TSG demonstrated within-group improvements in the field-based tests in three studies (8.1% to 79.0%), and within-group improvements in maximal oxygen uptake in four studies (6.5% to 31.0%), with significant favoring of TSG in most studies. Overall, TSG demonstrated significant benefits for overweight and obese populations compared to the control group, particularly in terms of improvements in body mass index, systolic blood pressures, cholesterol and triglyceride levels, and aerobic fitness. Future research ought to concentrate on tailoring responses to varying training volumes on an individualized basis.

3.
Genomics ; 114(2): 110309, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35131477

RESUMO

Daphnia sinensis is a widespread freshwater microcrustacean. The assembled D. sinensis genome totaled 131.58 Mb with 92.23% of the assembly anchored onto 10 chromosomes. Based on the whole genome information, we further compared the transcriptomic and epigenomic characterization among parthenogenetic females, sexual females and males in D. sinensis. Transcriptomic analysis showed that the up-regulated genes in males were mainly grouped into the cuticle, sex differentiation and methyl farnesoate synthesis, which might play a pivotal role in steering development and reproduction processes. By comparison, the highly expressed genes in parthenogenetic females were mainly grouped into energy metabolism, mitosis, and DNA replication, which might contribute to maintaining rapid production of parthenogenetic females, and nutrient uptake for the growth of neonates. The whole-genome DNA methylation analysis showed that the methylation rate in parthenogenetic females was higher than that in sexual females and males, which might contribute to its rapid response to environment stress.


Assuntos
Daphnia , Reprodução , Animais , Biologia , Daphnia/genética , Feminino , Masculino , Partenogênese/genética , Reprodução/genética , Diferenciação Sexual
4.
Molecules ; 28(11)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37298783

RESUMO

A one-step sulfurization method to fabricate Ni3S2 nanowires (Ni3S2 NWs) directly on a Ni foam (NF) was developed as a simple, low-cost synthesis method for use as a supercapacitor (SC), aimed at optimizing energy storage. Ni3S2 NWs have high specific capacity and are considered a promising electrode material for SCs; however, their poor electrical conductivity and low chemical stability limit their applications. In this study, highly hierarchical three-dimensional porous Ni3S2 NWs were grown directly on NF by a hydrothermal method. The feasibility of the use of Ni3S2/NF as a binder-free electrode for achieving high-performance SCs was examined. Ni3S2/NF exhibited a high specific capacity (255.3 mAh g-1 at a current density of 3 A g-1), good rate capability (2.9 times higher than that of the NiO/NF electrode), and competitive cycling performance (capacity retention of specific capacity of 72.17% after 5000 cycles at current density of 20 A g-1). Owing to its simple synthesis process and excellent performance as an electrode material for SCs, the developed multipurpose Ni3S2 NWs electrode is expected to be a promising electrode for SC applications. Furthermore, the synthesis method of self-growing Ni3S2 NW electrodes on 3D NF via hydrothermal reactions could potentially be applied to the fabrication of SC electrodes using a variety of other transition metal compounds.


Assuntos
Fontes de Energia Elétrica , Porosidade , Condutividade Elétrica , Eletrodos
5.
Pak J Med Sci ; 38(6): 1426-1430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991232

RESUMO

Objective: To analysis the relevant infections and risk factors of patients undergoing hemodialysis semi-permanent catheter (tunneled cuffed) placement during for maintenance hemodialysis. Methods: A total of 158 patients with chronic renal failure (CRF) End stage renal failure (ESRF) treated in our hospital from September 2018 to September 2021 were retrospectively analyzed. All the patients underwent semi-permanent catheter placement during maintenance hemodialysis. The occurrence of catheter-related infections in the patients were recorded. The patients with catheter-related infections were included in the infection group, and the others without infection in the non-infection group. The differences in hypertension, gender, diabetes, age, catheter indwelling time and dialysis time between the two groups were analyzed, and the distribution of pathogens in the patients with infections was analyzed. Results: The patients were followed up for 13 to 36 months, with an average of (22.18 ± 6.09) months. Among the 158 patients who underwent going semi-permanent catheter placement, 42 (26.58%) presented semi-permanent catheter-related infections, including four cases of catheter-related bacteremia, 16 cases of tunnel infection and 22 cases of catheter exit-site infection. Among total of 42 strains of pathogens were isolated from the 42 patients with catheter-related infections, including 243 strains of Gram-positive cocci were identified in 24/42(57.14%), and 163 strains of Gram-negative bacilli were identified 16/42(38.10%) and one starin of fungus was identified in 2/42 patients. Statistically significant differences were found in dialysis duration time, hypoalbuminemia, average mean age, diabetes and catheter indwelling time between patients with and without catheter-related infections (P < 0.05). Hypoalbuminemia, catheter indwelling time and diabetes were risk factors for catheter-related infections (P < 0.05). Conclusions: Patients with ESRF CRF are at risk and prone to catheter-related infections during hemodialysis using catheter, mainly tunnel infection and catheter exit-site infection. Gram-positive cocci are the main pathogens. Hypoalbuminemia, too long catheter indwelling time and diabetes are the risk factors for infections.

6.
J Cell Physiol ; 235(2): 1405-1416, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31347176

RESUMO

Breast cancer patients with high expression of aldehyde dehydrogenases (ALDHs) cell population have higher tolerability to chemotherapy since the cells posses a characteristic of breast cancer stem cells (BCSCs) that are resistant to conventional chemotherapy. In this study, we found that the ALDH-positive cells were higher in CD44+ CD24- and CD44+ CD24- ESA+ BCSCs than that in both BT549 and MDA-MB-231 cell lines but microRNA-7 (miR-7) level was lower in CD44+ CD24- and CD44+ CD24- ESA+ BCSCs than that in MDA-MB-231 cells. Moreover, miR-7 overexpression in MDA-MB-231 cells decreased ALDH1A3 activity by miR-7 directly binding to the 3'-untranslated region of ALDH1A3; while the ALDH1A3 expression was downregulated in MDA-MB-231 cells, the expressions of CD44 and Epithelium Specific Antigen (ESA) were reduced along with decreasing the BCSC subpopulation. Significantly, enforced expression of miR-7 in CD44+ CD24- ESA+ BCSC markedly inhibited the BCSC-driven xenograft growth in mice by decreasing an expression of ALDH1A3. Collectively, the findings demonstrate the miR-7 inhibits breast cancer growth via suppressing ALDH1A3 activity concomitant with decreasing BCSC subpopulation. This approach may be considered for an investigation on clinical treatment of breast cancers.


Assuntos
Aldeído Oxirredutases/genética , Neoplasias da Mama/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Aldeído Desidrogenase/metabolismo , Animais , Mama/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
7.
J Cell Physiol ; 235(3): 2183-2194, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31489631

RESUMO

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is aberrantly expressed in multiple myeloma (MM) patients, however, its role remains largely unknown. The present study aimed to investigate the effect of NY-ESO-1 knockdown on MM impact and provide evidence for targeting treatment of MM. Human MM U266 cells were infected with lentivirus-based small hairpin RNA-targeting NY-ESO-1 (LV-shNY-ESO-1). Cellular proliferation, colony-forming, migration, and invasion assays were employed. The expressions of cell cycle and epithelial-mesenchymal transition (EMT)-related molecules, MM growth, and mouse osteolytic lesions were evaluated. The results showed that the LV-shNY-ESO-1-U266 cells had a lower expression of NY-ESO-1 and a higher expressions of p21 and E-cadherin, and a weaker abilities of colony formation, drug-resistant to adriamycin, migration, and invasion than those of the control cells. Importantly, the knockdown of NY-ESO-1 inhibited significantly the U266 cell-induced MM growth and osteolytic lesions along with increasing the expressions of E-cadherin, p21, and p53 in mice challenged with LV-shNY-ESO-1-U266 cells. Collectively, our findings demonstrate that knockdown of NY-ESO-1 suppressed the U266 cell-induced MM growth and osteolytic lesions by inhibition of the MMs cell cycle and EMT. The NY-ESO-1 knockdown may be considered for future clinical trials in MM.


Assuntos
Proliferação de Células/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Mieloma Múltiplo/genética , Animais , Biomarcadores Tumorais/genética , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , New York
8.
Breast Cancer Res ; 22(1): 26, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143670

RESUMO

BACKGROUND: Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown. METHODS: We examined miR-7 expression in breast cancer and developed a BCSC-driven xenograft mouse model, to evaluate the effects of miR-7 overexpression on the decrease of the BCSC subset in vitro and in vivo. In addition, we determined how miR-7 decreased the BCSC subset by using the ALDEFLUOR, lentivirus infection, dual-luciferase reporter, and chromatin immunoprecipitation-PCR assays. RESULTS: MiR-7 was expressed at low levels in breast cancer tissues compared with normal tissues, and overexpression of miR-7 directly inhibited lncRNA XIST, which mediates the transcriptional silencing of genes on the X chromosome, and reduced epithelium-specific antigen (ESA) expression by increasing miR-92b and inhibiting slug. Moreover, miR-7 suppressed CD44 and ESA by directly inhibiting the NF-κB subunit RELA and slug in breast cancer cell lines and in BCSC-driven xenografts, which confirmed the antitumor activity in mice injected with miR-7 agomir or stably infected with lenti-miR-7. CONCLUSIONS: The findings from this study uncover the molecular mechanisms by which miR-7 inhibits XIST, modulates the miR-92b/Slug/ESA axis, and decreases the RELA and CD44 expression, resulting in a reduced BCSC subset and breast cancer growth inhibition. These findings suggest a potentially targeted treatment approach to breast cancer.


Assuntos
Neoplasias da Mama/prevenção & controle , Molécula de Adesão da Célula Epitelial/metabolismo , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , Fatores de Transcrição da Família Snail/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Molécula de Adesão da Célula Epitelial/genética , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/patologia , RNA Longo não Codificante/genética , Fatores de Transcrição da Família Snail/genética , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Membr Biol ; 250(5): 433-440, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28647752

RESUMO

Electric fields (EF) can induce some physiological or biological effects in neural tissues, which have been explored in many applications such as electroporation. The key to understand the possible underlying mechanisms of such effects tend to be the induced transmembrane potential. Although transmembrane potentials have already been the subject of many theoretical studies, most previous works concerning this topic are mainly focused on the situations of isolated cells. In previous studies, cells are often considered to be three-compartment models with different electroconductivities in different regions (the three compartments are often intracellular regions, membrane, and extracellular regions). In the present paper, we utilize a finite element method (FSM) (with the help of COMSOL®) to calculate the induced transmembrane potential by the applied EF for a model of two neurons, which may have significant difference on electroporation.


Assuntos
Análise de Elementos Finitos , Potenciais da Membrana/fisiologia , Modelos Biológicos , Tecido Nervoso/citologia , Tecido Nervoso/metabolismo , Animais , Humanos
11.
Acta Biochim Biophys Sin (Shanghai) ; 49(9): 800-807, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28910976

RESUMO

Isochlorogenic acid A, also called 3,5-dicaffeoylquinic acid (3,5-diCQA), is a widespread phenolic compound in the plant. Recent studies have shown that it has antioxidant and anti-inflammatory activity. In addition, oxidative stress and inflammation induced by solar ultraviolet radiation is a very significant reason for skin depigmentation. Therefore, in this study, we evaluated the effect of 3,5-diCQA on B16 cells and explored its molecular mechanism. Results showed that 3,5-diCQA upregulated intracellular melanin production in a time- and dose-dependent manner. Tyrosinase (TYR) activity was also increased after treatment with 3,5-diCQA in a dose-dependent manner. Expressions of TYR, TYR-related protein1, TYR-related protein2, and microphthalmia-associated transcription factor were upregulated in a dose-dependent manner after 48 h of treatment with 3,5-diCQA. Results also showed that 3,5-diCQA promoted the phosphorylation of Akt at Thr308 and glycogen synthase kinase-3ß at Ser 9. Moreover, 3,5-diCQA increased the content of ß-catenin in cell cytoplasm and nucleus by reducing the content of phosphorylated ß-catenin (p-ß-catenin). All these results suggest that 3,5-diCQA may mediate the acceleration of melanin synthesis by the ß-catenin signal pathway.


Assuntos
Ácido Clorogênico/análogos & derivados , Melaninas/biossíntese , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ácido Clorogênico/química , Ácido Clorogênico/farmacologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
12.
Molecules ; 22(12)2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29182558

RESUMO

Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-yl)methoxy)phenyl)-3-phenylprop-2-en-1-one (PMPP) was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP) in this study. Further investigations revealed that Akt and GSK3ß were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents.


Assuntos
Chalconas/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Melaninas/biossíntese , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Chalconas/química , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Melanoma Experimental , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/química
13.
Bioorg Med Chem ; 24(21): 5440-5448, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27622747

RESUMO

A new series of chalcone derivatives 1-18, bearing isoxazole moieties were designed and synthesized, and biologically evaluated for their activity on mushroom tyrosinase and melanin synthesis in murine B16 cells. The result indicated that most of prepared compounds 1-18 showed potent activating effect on tyrosinase, especially for 1-2, 4, 6-7, 9 and 15. Among them, compounds 2, 4 and 9 demonstrated the best activity with EC50=1.3, 2.5 and 3.0µmol·L-1 respectively, much better than the positive control 8-methoxypsoralan (8-MOP, EC50=14.8µmol·L-1); In B16 cells, all the tested compounds exhibited a stronger activity on melanogenesis than 8-MOP (with the value of 115%). It was interesting that derivatives substituted with halogen (1, 2, 4, 5, 7, 9) were generally more potent. Compounds 2 (463%) and 18 (438%) with 3 and 4-fold potency compared with 8-MOP respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo.


Assuntos
Agaricales/enzimologia , Chalcona/análogos & derivados , Isoxazóis/síntese química , Isoxazóis/farmacologia , Melaninas/biossíntese , Monofenol Mono-Oxigenase/biossíntese , Vitiligo/tratamento farmacológico , Animais , Sobrevivência Celular/efeitos dos fármacos , Chalcona/química , Chalcona/farmacologia , Relação Dose-Resposta a Droga , Isoxazóis/química , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
14.
Bioorg Med Chem ; 24(22): 5960-5968, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27713014

RESUMO

Furocoumarins, isolated from Psoralen corylifolia L., were found to be the most effective drug in the treatment of vitiligo nowadays. Twenty-five furocoumarin derivatives were thus designed and synthesized in order to improve the melanogenesis in B16 cells for the first time. Among them, twenty-three compounds were more potent than the positive control (8-MOP), the commonly used drug for vitiligo in clinic. Noticeably, compounds 6m (350.5%) and 6p (313.1%) based on the scaffold of 6k (2H-benzofuro[2,3-h]chromen-2-one) were nearly 3-fold stronger than 8-MOP (114.50%). The in vitro melanin synthesis evaluation of these structurally diverse analogues had also led to an outline of structure-activity relationship.


Assuntos
Furocumarinas/farmacologia , Melaninas/antagonistas & inibidores , Vitiligo/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ficusina/química , Furocumarinas/química , Furocumarinas/isolamento & purificação , Melaninas/biossíntese , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Vitiligo/metabolismo
15.
Apoptosis ; 20(1): 50-62, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25425103

RESUMO

High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma.


Assuntos
Benzoxazóis/farmacologia , Complexos Multiproteicos/metabolismo , Neuroblastoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Xenoenxertos , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos Nus , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Transdução de Sinais/efeitos dos fármacos
16.
Stem Cells ; 32(11): 2858-68, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25070049

RESUMO

Epithelial-mesenchymal transition (EMT) contributes to tumor invasion and metastasis in many cancers and correlates highly with the acquisition of cancer stem cell (CSC) characteristics. EMT also correlates with changes in specific microRNAs (miRNAs) that have already been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. Here, we show that miR-7, which was downregulated in breast CSCs (BCSCs) isolated from the human MCF-7 and MDA-MB-231 cell lines, inhibited cell invasion and metastasis, decreased the BCSC population and partially reversed EMT in MDA-MB-231 cells by directly targeting the oncogene, SETDB1. The conspicuous epigenetic transition induced by miR-7 overexpression was found not only in MDA-MB-231 cells but also in BCSC xenograft tumors. MiR-7 inhibited the metastasis of BCSCs in lungs, kidneys, and adrenal glands of NOD/SCID mice. ChIP-polymerase chain reaction result suggested that the SETDB1 induced STAT3 expression by binding to the promoter of STAT3. MiR-7-mediated downregulation of SETDB1 resulted in the suppression of STAT3, which led to the downregulation of c-myc, twist, and mir-9. In addition, the downregulation of miR-7 in BCSCs may be indirectly attributed to lincRNA HOTAIR by modulating the expression of HoxD10 that promotes the expression of miR-7. These findings demonstrate that miR-7 was a tumor suppressor and that the overexpression of miR-7 might serve as a good strategy for treating highly invasive breast cancer.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , MicroRNAs/metabolismo , Proteínas Metiltransferases/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Células-Tronco Neoplásicas/metabolismo
17.
Cancer Cell Int ; 15: 24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25792974

RESUMO

BACKGROUND: Emerging evidence indicates that dysregulated long intervening non-coding RNA (lincRNA) HOTAIR correlates highly with tumor invasion and metastasis but a link between the high expression of HOTAIR and the metastatic cascade of cancer stem cells (CSCs) needs to be further studied. The purpose of this study was to investigate the effect of down-regulated HOTAIR expression on tumorgeniesis and metastasis of epithelial ovarian cancer (EOC) CSCs. CD117(+)CD44(+)CSCs were isolated from human EOC SKOV3 cell line by using a magnetic-activated cell sorting system, and were then transfected with the expression vector-based small hairpin RNA targeting HOTAIR; the stably transfected cells were selected for the study. Colony-forming, wound-healing, cellular metastasis and tumorigenicity assays were performed. RESULTS: The results demonstrated that the HOTAIR expression in clinical EOC tissues and SKOV3 CD117(+)CD44(+)CSCs was higher than in SKOV3 tumor tissues and non-CD117(+)CD44(+)CSCs. The CD117(+)CD44(+)-shHOTAIR showed an inhibited HOTAIR expression, reduced cell migration and invasion than CD117(+)CD44(+)- scramble, suggesting the inhibition of an epithelial-mesenchymal transition. Moreover, the downregulated HOTAIR expression in CD117(+)CD44(+) CSCs significantly decreased the tumor growth and lung metastasis in xenograft mice. CONCLUSION: Our findings demonstrated the shHOTAIR-mediated down-regulation of the HOTAIR expression in CD117(+)CD44(+) CSCs can be a promising new opportunity for future clinical trials.

18.
J Transl Med ; 12: 68, 2014 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-24625224

RESUMO

BACKGROUND: Genetically modified cells have been shown to be one of the most effective tumor vaccine strategies. However, in many cases, such as in melanoma, induction of a potent immune responses against the disease still remains a major challenge. Thus, novel strategies to reinforce tumor vaccine efficacy are needed. Using microRNA (miR) and Zinc-finger E-box binding homeobox (ZEB) have received much attention for potentially regulating tumor progression. To elicit a potent antitumor efficacy against melanoma, we used tumor vaccine in combination with miR200c overexpression or ZEB1 knockdown to assess the efficacy of treatment of murine melanoma. METHODS: B16F10 cell vaccine expressing interleukin 21 (IL-21) in the glycosylpho- sphatidylinositol (GPI)-anchored form (B16F10/GPI-IL-21) were developed. The vaccine was immunized into mice challenged by B16F10 cells or B16F10 cells stably transduced with lentiviral-miR200c (B16F10/miR200c) or transfected with the ZEB1-shRNA recombinant (B16F10/shZEB1) or the B16F10/GPI-IL-21 vaccine. The immune responses, tumorigenicity and lung metastasis in mice were evaluated, respectively. RESULTS: The vaccination with B16F10/GPI-IL-21 markedly increased the serum cytokine levels of IFN-γ, TNF-α, IL-4 and decreased TGF-ß level as well as augmented the cytotoxicity of splenocytes in immunized mice compared with control mice. In addition, the tumor vaccine B16F10/GPI-IL-21 significantly inhibited the tumor growth and reduced counts of lung metastases in mice challenged by B16F10/GPI-IL-21, B16F10/shZEB1 and B16F10/miR200c respectively compared with the control mice challenged by B16F10 cells. The efficacy mechanisms may involve in reinforcing immune responses, increasing expression of miR200c, E-cadherin and SMAD-7 and decreasing expression of TGF-ß, ZEB1, Vimentin and N-cadherin in tumor tissues from the immunized mice. CONCLUSIONS: These results indicate that the tumor vaccine B16F10/GPI-IL-21 in combination with miR200c overexpression or ZEB1 knockdown effectively inhibited melanoma growth and metastasis a murine model. Such a strategy may, therefore, be used for the clinical trials.


Assuntos
Vacinas Anticâncer/imunologia , Regulação Neoplásica da Expressão Gênica , Glicosilfosfatidilinositóis/imunologia , Proteínas de Homeodomínio/genética , Interleucinas/imunologia , Fatores de Transcrição Kruppel-Like/genética , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , MicroRNAs/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/sangue , Citotoxicidade Imunológica/genética , Transição Epitelial-Mesenquimal/genética , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/metabolismo , Imunização , Fatores de Transcrição Kruppel-Like/metabolismo , Melanoma Experimental/sangue , Melanoma Experimental/genética , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Metástase Neoplásica/genética , Metástase Neoplásica/imunologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Baço/metabolismo , Baço/patologia , Transdução Genética , Transfecção , Homeobox 1 de Ligação a E-box em Dedo de Zinco
19.
Biopolymers ; 101(5): 496-503, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24122355

RESUMO

This study investigates the application of Plasma-polymerized pyrrole (ppPY) as bioactive platform for DNA immobilization and cell adhesion based on the fundamental properties of ppPY, such as chemical structure, electrochemical property, and protein adsorption. Variations in electrochemical properties of the ppPY film deposited under different plasma conditions before and after DNA immobilization were measured using electrochemical impedance spectroscopy (EIS). The equilibrium concentration of the probe DNA immobilized on the ppPY surface was deduced by detecting the variations in the surface charge transfer resistance (Rct ) of the ppPY films after DNA immobilization with different concentrations. In addition, the detection limit of the target DNA hybridization with probe DNA, the association constant, Ka , and the dissociation constant were deduced from Langmuir isotherm equations simulated using the experimental data collected by EIS. Moreover, inverted microscope was used to observe the cell adhesions onto the surface of the ppPY films prepared under different plasma conditions. Different adhesive behaviors of cells were observed, demonstrating that ppPY films could be an alternative biomaterial used as the sensitive layer for DNA sensor or cell adhesion.


Assuntos
DNA/análise , Gases em Plasma/química , Polimerização , Pirróis/química , Calibragem , Adesão Celular , Linhagem Celular Tumoral , Sondas de DNA/metabolismo , Espectroscopia Dielétrica , Eletrodos , Humanos , Cinética , Hibridização de Ácido Nucleico
20.
Cell Biol Int ; 38(4): 452-61, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24339410

RESUMO

Zinc-finger E-box binding homeobox 1 (ZEB1) is a master regulator of epithelial-mesenchymal transition (EMT) and has been implicated in primary epithelial cancer biological processes, such as invasion and metastasis. However, the role of ZEB1 in progression of melanoma and cancer stem cells (CSCs) remains obscure. In this study, the recombinant plasmids of t3 shRNAs targeting mouse ZEB1 were constructed and transfected into melanoma B16F10 cells. The stable transfected cells were selected and the characteristics of ZEB1 downregulated B16F10 cells was assessed. The tumourigenicity of CD44(+) CD133(+) CSCs isolated from B16F10 cells stably transfected with the ZEB1-shRNA2 recombinant was also assessed. ZEB1-shRNAs B16F10 showed a lower expression of ZEB1 and vimentin, weaker migration, invasiveness, colony forming, and proliferation, and a lower tumourigenicity than the control cells. The tumourigenicity of the ZEB1-shRNA2 CD44(+) CD133(+) CSCs was also inhibited. In conclusion, ZEB1-shRNA2-mediated downregulation of ZEB1 expression in B16F10 cells and CSCs is involved in the inhibition of the EMT process. ZEB1 may be a potential target in melanoma targeted.


Assuntos
Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Neoplásicas/metabolismo , Vimentina/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Transformação Celular Neoplásica , Regulação para Baixo , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/genética , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/genética , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neoplásicas/citologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco
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