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1.
Adv Healthc Mater ; : e2304506, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441392

RESUMO

Fluorescence imaging in the second near-infrared window (NIR-II) is burgeoning because of its higher imaging fidelity in monitoring physiological and pathological processes than clinical visible/the second near-infrared window fluorescence imaging. Notably, the imaging fidelity is heavily dependent on fluorescence agents. So far, indocyanine green, one of the polymethine dyes, with good biocompatibility and renal clearance is the only dye approved by the Food and Drug Administration, but it shows relatively low NIR-II brightness. Importantly, tremendous efforts are devoted to synthesizing polymethine dyes for imaging preclinically and clinically. They have shown feasibility in the customization of structure and properties to fulfill various needs in imaging and therapy. Herein, a timely update on NIR-II polymethine dyes, with a special focus on molecular design strategies for fluorescent, photoacoustic, and multimodal imaging, is offered. Furthermore, the progress of polymethine dyes in sensing pathological biomarkers and even reporting drug release is illustrated. Moreover, the NIR-II fluorescence imaging-guided therapies with polymethine dyes are summarized regarding chemo-, photothermal, photodynamic, and multimodal approaches. In addition, artificial intelligence is pointed out for its potential to expedite dye development. This comprehensive review will inspire interest among a wide audience and offer a handbook for people with an interest in NIR-II polymethine dyes.

2.
BMC Pregnancy Childbirth ; 22(1): 171, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236324

RESUMO

OBJECTIVE: The current study was undertaken to investigate the relationship between antimüllerian hormone (AMH) and polycystic ovarian syndrome (PCOS) phenotypes and to determine whether AMH is associated with pregnancy outcomes in infertile women undergoing their first in vitro fertilization (IVF) treatment. METHODS: We performed a retrospective cohort study of 2973 infertile women, including 418 women with PCOS undergoing their first IVF treatment at a private fertility center from January 2014 to March 2018. Women were stratified into three groups using cutoffs defined by the 25th and 75th percentiles of the serum AMH level: 746 women had AMH ≤ 2.25 ng/mL; 1486 women had AMH between 2.25 to 5.71 ng/mL; and 741 women had AMH > 5.71 ng/mL. Endocrine characteristics, PCOS phenotypes, stimulation outcomes, pregnancy outcomes were compared among these groups. When there were any statistical differences (P < 0.05) among the three groups, Bonferroni test was performed as post-hoc tests to determine where the statistical differences existed. To assess the relationships between AMH and pregnancy outcomes in total patients and PCOS patients, logistic regression analysis, adjusted for potential confounding covariates, were performed. RESULTS: Women with high AMH had greater prevalence of hyperandrogenism (HA), polycystic ovarian morphology (PCOM) and amenorrhea than women with low or average AMH. The clinical pregnancy rate were significantly higher in the high-AMH group compared with low- and average-AMH groups (69.9% vs. 58.8% and 64.7% respectively; P < 0.001). The live birth rate was significantly lower in women with AMH ≤ 2.25 ng/mL compared with average- and high-AMH groups (47.6% vs. 55.2 and 59.5% respectively; P < 0.001). However, after controlling for maternal age, oocyte yield, as well as other confounders, AMH was no longer associated with a higher live birth rate (aOR 1.037, 95% CI 0.853-1.261, P = 0.717; aOR 1.099, 95% CI 0.858-1.408, P = 0.455, respectively) and clinical pregnancy rate (aOR 1.064, 95% CI 0.834-1.359, P = 0.617; aOR 1.181, 95% CI 0.875-1.595, P = 0.276, respectively). Moreover, pregnancy outcomes did not differ in PCOS women according to AMH quartiles. CONCLUSION: Increased AMH levels associated with PCOS severity and greater ovarian stimulation. However, AMH was not associated with clinical pregnancy rate and live birth rate after controlling for other confounders in women undergoing IVF. Thus, AMH should not be used to alter clinical decisions and exclude patients based on a low or even undetectable AMH value.


Assuntos
Hormônio Antimülleriano/análise , Hormônio Antimülleriano/sangue , Fenótipo , Síndrome do Ovário Policístico/sangue , Resultado da Gravidez , Taxa de Gravidez , Adulto , Transferência Embrionária , Feminino , Fertilização in vitro/métodos , Humanos , Infertilidade Feminina/terapia , Gravidez , Estudos Retrospectivos
3.
Immunol Invest ; 51(5): 1330-1346, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34132158

RESUMO

Understanding maternal immune tolerance is crucial for the development of therapeutics for immunological pregnancy complications. Decidual regulatory T cells (Tregs) play a pivotal role in the maintenance of maternal immune tolerance. Using a murine allogeneic pregnancy model in the current study, we identified the up-regulation of gonadotropin-releasing hormone receptor (GnRHR) in decidual T cell subsets including CD4+ conventional T cells, CD8+ T cells, and CD4+Foxp3+ Tregs. Using a lentivirus-mediated GnRHR overexpression system and a GnRHR agonist, we found that GnRHR activation decreased the expression of Treg functional molecules such as IL10 (IL-10), IL-35 subunit EBI3 (Ebi3), IL2RA (CD25), TNFRSF18 (GITR), ICOS, and Treg master regulator FOXP3. The functional analysis indicated that GnRHR activation impairs the ability of Tregs to inhibit conventional T cell proliferation. We also revealed that GnRHR activation suppressed the mechanistic target of rapamycin (mTOR) signaling in GnRHR-overexpressing splenic Tregs (Wild type C57BL/6 J background) and decidual Tregs. MHY1485, a potent mTOR activator, effectively abolished the effect of the GnRHR agonist and promoted the immunosuppressive capability of Tregs. Furthermore, in an adoptive transfer model, Treg-specific GnRHR knockdown increased Foxp3 expression in decidual Tregs while decreasing the production of IFN-γ and IL-17 in decidual effector CD4+ T cells and reducing the production of IFN-γ in decidual effector CD8+ T cells. Taken together, the present study unveils a novel mechanism by which the immunosuppressive function of decidual Tregs is modulated, and deepens our understanding of maternal immune tolerance.


Assuntos
Tolerância Imunológica , Gravidez , Receptores LHRH , Linfócitos T Reguladores , Serina-Treonina Quinases TOR , Animais , Linfócitos T CD8-Positivos/imunologia , Feminino , Fatores de Transcrição Forkhead/imunologia , Tolerância Imunológica/imunologia , Camundongos , Gravidez/imunologia , Receptores LHRH/imunologia , Linfócitos T Reguladores/imunologia , Serina-Treonina Quinases TOR/imunologia
4.
Reprod Sci ; 28(10): 2847-2854, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33959892

RESUMO

This retrospective cohort study aimed to explore the optimal endometrial preparation protocols among different maternal age groups. A total of 16,867 frozen-thawed embryo transfer (FET) cycles were categorized into three groups based on endometrial preparation protocols: Natural cycle (NC n = 3893), artificial cycles (AC, n = 11456) and AC with GnRH-a pretreatment (AC+GnRH-a, n = 1518). To account for repeat cycles, a generalized estimating equation (GEE) method was applied to examine the associations between cycle regimens and pregnancy outcomes. Subgroup analyses were conducted to evaluate the best preparation methods for different maternal age groups. Primary outcomes were live birth and early miscarriage rates. After completing GEE, in overall population, the live birth rate [(NC as reference; AC: adjusted odds ratio (aOR) = 0.837, 95% confidential interval (CI) 0.771-0.908; AC+GnRHa: aOR = 0.906, 95%CI 0.795-1.031)] in NC was significantly higher than that in AC, while comparable that in AC+GnRH-a. The early miscarriage rate (AC: aOR = 1.420, 95%CI 1.225-1.646; AC+GnRHa: aOR = 1.545, 95%CI 1.236-1.931) was significantly lower in NC compared to either AC group. Subgroup analysis showed that in younger women, the incidences of live birth (AC: aOR = 0.900, 95%CI 0.804-1.007; AC+GnRHa: aOR = 1.091, 95%CI 0.904-1.317) were equivalent between groups, with a slightly higher in AC+GnRH-a. Early miscarriage rate (AC: aOR = 1.462, 95%CI 1.165-1.835; AC+GnRHa: aOR = 1.137, 95%CI 0.948-1886) was only significantly lower in NC compared to that in AC. In older women, the live birth rate (AC: aOR = 0.815, 95%CI 0.722-0.920; AC+GnRHa: aOR = 0.759, 95%CI 0.627-0.919) was significantly higher, and early miscarriage rate (AC: aOR = 1.353, 95%CI 1.118-1.638; AC+GnRHa: aOR = 1.704, 95%CI 1.273-2.280) was significantly lower in NC compared to either AC group. Our study demonstrated that NC is associated with lower early miscarriage late in overall IVF population. There is a mild favor of AC+GnRH-a in younger women, while the priority of NC is remarkable in older women. Maternal age should be a considerable factor when determining endometrial preparation method for FET.


Assuntos
Criopreservação/métodos , Transferência Embrionária/métodos , Endométrio/metabolismo , Fertilização in vitro/métodos , Idade Materna , Resultado da Gravidez/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Oócitos/metabolismo , Gravidez , Estudos Retrospectivos
5.
J Reprod Immunol ; 144: 103282, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33607547

RESUMO

Polycystic ovary syndrome (PCOS) is described as a low-grade chronic inflammatory state. However, there are limited studies on the specific endometrial immune status of PCOS patients. Whether this endometrial immune cell pattern is intrinsic to PCOS or the consequence of PCOS-associated obesity is a subject of debate. This study retrospectively included one hundred women diagnosed with PCOS and ninety-five normal fertile controls, which further divided into four groups (normoweight PCOS; overweight PCOS; normoweight control; overweight control) based on body mass index. The percentages of endometrial CD68+ macrophages (1.97 % vs. 1.17 %; P < 0.001), CD163+ M2 macrophages (2.30 % vs. 1.83 %; P = 0.001), CD1a+ iDCs (0.044 % vs. 0.029 %; P = 0.002), CD83+ mDCs (1.72 % vs. 1.07 %; P < 0.001) and CD8+ T cells (2.82 % vs. 1.95 %; P < 0.001) were significantly higher in normoweight PCOS women than normoweight controls. The percentage of CD68+ macrophages (2.09 % vs. 1.15 %; P < 0.001) was significantly higher in overweight PCOS women compared with overweight controls. In multivariant linear regression analysis, participants' PCOS status was the main predictors of endometrial CD68+ macrophages, CD163+ M2 macrophages, CD1a+ iDCs, CD83+ mDCs and CD8+ T cells in the whole study population. Additionally, in PCOS group, positive correlations were found between endometrial CD56+ NK, CD163+ M2 macrophages and QUICKI, indicating there was an association between endometrial immune cells and insulin resistance in PCOS women. Our study suggests that women with PCOS have altered endometrial immune cells, which may reflect a state of chronic low grade inflammation. The chronic inflammation, independent of obesity, may help understand the pathophysiologic mechanisms of intrinsic PCOS.


Assuntos
Endométrio/imunologia , Hiperandrogenismo/imunologia , Resistência à Insulina/imunologia , Síndrome do Ovário Policístico/complicações , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígeno CD56/metabolismo , Estudos de Casos e Controles , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Endométrio/citologia , Endométrio/patologia , Feminino , Voluntários Saudáveis , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/diagnóstico , Imunoglobulinas/metabolismo , Insulina/sangue , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/patologia , Receptores de Superfície Celular/metabolismo , Estudos Retrospectivos , Testosterona/sangue , Antígeno CD83
6.
Sci Total Environ ; 729: 138635, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32498153

RESUMO

Accurate estimation of evapotranspiration (ET) over regional scale is essential for ecohydrological research, agricultural production, and water resources management. However, few studies have been done to estimate regional ET in data lacking, highly heterogeneous arid areas such as the Agricultural-Pastoral Ecotone in Northwest China (APENC). In this study, we compared three actual ET-estimation methods driven by Weather Research and Forecasting (WRF) model in a semi-arid region. We selected the state of the art Weather Research and Forecasting-Community Land Model 4.0 (WRF-CLM4.0) model, the widely used WRF-Noah model and an empirical Complementary Relationship (CR) model to compare their model structures and mechanisms of estimating daily ET in the study region. The WRF model was chosen to address the problem of data scarcity in the study region and to derive model input for ET estimation with high spatial resolution. The seasonal and pooled performances of the three models were verified with in situ observations. Results indicate that the WRF-CLM4.0 model shows a better applicability in the study region, with a superior performance for the pooled datasets (Pearson correlation coefficient [r] = 0.89, root-mean-square error [RMSE] = 0.66 mm/d and Nash-Sutcliffe efficiency coefficient [NSE] = 0.90), while the CR model has a comparable performance (r = 0.91, RMSE = 0.86 mm/d and NSE = 0.85) and the WRF-Noah model shows the worst performance (r = 0.82, RMSE = 0.94 mm/d and NSE = 0.81). The differences are mainly caused by different representations of the land surface characteristics and hydrology of the study region by the three different models. Our analysis shows that the WRF-CLM4.0 model and the CR model are more applicable to the APENC than the WRF-Noah model. For regional applications, the CR model, with fewer parameters and simpler structure, is able to capture the local characteristic and well-suited for data lacking, highly heterogeneous landscapes such as the APENC.

7.
Phys Chem Chem Phys ; 20(31): 20571-20574, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30058658

RESUMO

The electron localization in Nb-doped CaMnO3 is analyzed in terms of the space and energy distribution of electronic states employing first-principles calculations. The energy difference of Mn 3d states and Nb 4d states makes NbO6 octahedra impede electrical conduction, so the random distribution of Nb in lattices leads to the localization of electrons near the bottom of the conduction bands. Therefore, although more carriers are introduced when Nb-doping content increases, both the electrical conductivity and absolute thermopower decrease in Nb heavy doped CaMnO3. The calculated transport properties agree well with the experimental data, supporting the analysis of localization.

8.
Oncotarget ; 8(52): 90132-90143, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29163816

RESUMO

Ovarian cancer is one of the major cancer types. NK-92 cell line, which has consistently and reproducibly high anti-tumor cytotoxicity, may be used for immunotherapy against ovarian cancer. Understanding the mechanisms that regulate the anti-tumor activity of NK-92 cells is important for developing novel therapeutic strategies. In the current study, using an ovarian cancer xenograft mouse model, we identified the up-regulation of sestrin2 (SESN2) and sestrin3 (SESN3) in intratumoral NK-92 cells. Lentivirus-transduced NK-92 cells, which overexpressed SESN2 or SESN3 after doxycycline treatment, exhibited less expression of activating receptors, perforin and granzyme B. Overexpression of SESN2 and SESN3 impaired tumoricidal effect of NK-92 cells both in vitro and in vivo. Furthermore, overexpression of SESN2 and SESN3 inhibited mTORC1 signaling while promoting AMPK signaling in NK-92 cells. Taken together, our data highlights the crucial effects of SESN2 and SESN3 on NK-92 cell-mediated anti-ovarian cancer activity. This study might be valuable for designing a novel therapeutic strategy for ovarian cancer.

9.
J Oral Sci ; 58(4): 555-560, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28025440

RESUMO

The aim of the present study was to evaluate the association of single nucleotide polymorphisms (SNPs) in toll-like receptor 4 (TLR4) with chronic obstructive pulmonary disease (COPD) in Han Chinese patients with chronic periodontitis (CP). Six candidate SNPs of TLR4-rs10759930, rs10983755, rs11536879, rs1927907, rs11536889 and rs7873784-and 18 haplotype-tagging SNPs (tagSNPs) were genotyped in 339 patients with chronic periodontitis only (CP group), and 373 CP patients with COPD (CP with COPD group). The genotype distribution and allele frequencies of TLR4 rs1927907 among the CP (AA: 26, 8.5%, AG: 109, 35.5%, GG: 172, 56.0%) and CP with COPD (AA: 41, 12.0%, AG: 143, 41.7%, GG: 159, 46.4%) groups were significantly different (P = 0.039). After adjusting for age, sex, smoking status, and oral hygiene habits, CP patients carrying the AG polymorphism in TLR4 rs1927907 were found to be more susceptible to concomitant COPD than those carrying the GG genotype (P = 0.005, OR = 1.94, 95% CI for OR: 1.22-3.03). In conclusion, TLR4 gene polymorphism plays a role in the common pathophysiology of CP and COPD, indicating that CP patients with TLR4 gene rs1927907 polymorphism may be more susceptible to COPD.(J Oral Sci 58, 555-560, 2016).


Assuntos
Etnicidade , Predisposição Genética para Doença , Periodontite/complicações , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Receptor 4 Toll-Like/genética , Idoso , China , Doença Crônica , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações
10.
Biol Reprod ; 94(6): 144, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26962121

RESUMO

Dibutyl phthalate (DBP) is used worldwide in solvents and plasticizers. The cytotoxicity and potential tumorigenic effect of DBP have been reported. DBP has also been shown to impact reproductive function. In this study, to further evaluate the effects of DBP on granulosa cells (GCs), we treated rat GCs in vitro with DBP before evaluation of the biological alterations of these GCs. We found that DBP did not induce significant GC death at the tested concentrations. However, follicle-stimulating hormone (FSH)-induced KIT ligand (KITLG) expression in GCs was significantly reduced at both mRNA and protein levels by DBP treatment in a dose-dependent manner. The down-regulation of KITLG was due to the down-regulation of expression of FSH receptor (FSHR) in GCs. Down-regulation of FSHR impaired FSH-induced intracellular signaling in GCs, demonstrated by decreased phosphorylation of AKT and mechanistic target of rapamycin (mTOR). Furthermore, DBP treatment also reduced FSH-induced expression of hypoxia-inducible factor 1-alpha (HIF1A), which is an important signaling component for KITLG expression. Other FSH-induced biological effects, such as production of estradiol and progesterone, as well as GC proliferation, were also suppressed by DBP. Therefore, our study discovered a unique mechanism underlying the toxicity of DBP on GCs. These findings may initiate the development of novel therapeutic interventions for DBP-induced damage to GCs.


Assuntos
Dibutilftalato/toxicidade , Hormônio Foliculoestimulante/metabolismo , Células da Granulosa/efeitos dos fármacos , Plastificantes/toxicidade , Receptores do FSH/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Feminino , Células da Granulosa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos Sprague-Dawley , Fator de Células-Tronco/metabolismo
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(10): 3197-201, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30246510

RESUMO

Cu(InxGa1-x)Se2(CIGS) precursor films were prepared on ITO glass with potentiostatic electrodeposition. High quality CIGS films were obtained by selenization of the precursor films at high temperature in tubular furnace full of argon gas. X-ray diffraction (XRD), scanning electron microscopy (SEM) and UV-Vis-NIR spectroscopy were used to characterize the structure, morphology, composition and Vis-NIR absorption of CIGS films, respectively. XRD results show the selenized CIGS films have a preferential orientation (112) with average crystallite of 24.7 nm. Raman spectroscopy reveals that the CIGS films are pure quaternaryphases with chalcopyrite structure, and without binary or ternary phases in the films. Vis-NIR measurements determine that the bandgap of CIGS increases with the increase of Ga concentration in the film. When the Ga concentration is 5.41%, its bandgap is about 1.11 eV, and the calculated ratio of Ga to (Ga+In) is 16.3%, which is less than the ratio of Ga to (Ga+In), 21.4%, measured by SEM. This indicates that crystallinity of CIGS filmsneeds to be further improved. All the measurements demonstratethat optimum ITO/CIGS has a promising application in bifacial solar cells. In this paper, we provide a newmethodtoelectrodeposit low cost CIGS precursor films and a new method forselenization ofthe precursor films at high temperature. As a result, theuniform and compact CIGS films with good adhesion on ITO are successfully fabricated by these methods. The above characterization show that we have obtained CIGS films with high crystallinity, near stoichiometry, few impurity phases and superior light absorption. Electrodeposition, like magnetron sputtering, is very suitable for large-scale industrial production. The research work in this paper is therefore important and considerable to massive production of electrodeposition of CIGS films.

12.
Colloids Surf B Biointerfaces ; 136: 752-60, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26519937

RESUMO

As an attractive technique for the improvement of biomaterials, Plasma immersion ion implantation (PIII) has been applied to modifying the titanium material for dental implant application. The present study investigated the cytocompatibility and early osseointegration of fluoride-ion-implanted titanium (F-Ti) surface and implants, both characterizing in their composition of titanium oxide and titanium fluoride. The cytocompatibility of F-Ti was evaluated in vitro by using scanning electron microscope, Cell Counting Kit-8 assay, alkaline phosphatase activity assay, and quantitative real-time polymerase chain reaction. The results showed that the F-Ti weakened the effects that Porphyromonas gingivalis exerted on the MG-63 cells in terms of morphology, proliferation, differentiation, and genetic expression when MG-63 cells and Porphyromonas gingivalis were co-cultured on the surface of F-Ti. Meanwhile, the osteogenic activity of F-Ti implants was assessed in vivo via evaluating the histological morphology and estimating histomorphometric parameters. The analysis of toluidine blue staining indicated that the new bone was more mature in subjects with F-Ti group, which exhibited the Haversian system, and the mean bone-implant contact value of F-Ti group was slightly higher than that of cp-Ti group (p>0.05). Fluorescence bands were wider and brighter in the F-Ti group, and the intensity of fluorochromes deposited at the sites of mineralized bone formation was significantly higher for F-Ti surfaces than for cp-Ti surfaces, within the 2nd, 3rd and 4th weeks (p<0.05). An indication is that the fluoride modified titanium can promote cytocompatibility and early osseointegration, thus providing a promising alternative for clinical use.


Assuntos
Materiais Biocompatíveis , Implantes Dentários , Fluoretos/química , Osseointegração , Titânio/química , Linhagem Celular , Humanos , Propriedades de Superfície
13.
Oncotarget ; 6(34): 36231-44, 2015 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-26460549

RESUMO

MicroRNA (miRNA)-25 is a small non-coding RNA that has been implicated in the tumorigenesis of many cancers, but little is known on the role of miR-25 in HCC metastasis. We hereby found that miR-25 was significantly upregulated in clinical HCC tissues compared with normal liver tissues. We also revealed that miR-25 dramatically stimulates HCC cell growth and activates the epithelial-mesenchymal transition (EMT). MiR-25 is activated by the WNT/ß-catenin signaling pathway, and exerts its pro-metastatic function by directly inhibiting the Rho GDP dissociation inhibitor alpha (RhoGDI1). Downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. MiR-25 levels are positively correlated with ß-catenin expression, whereas negatively correlated with the level of RhoGDI1 in HCC. Our findings provide new insights into the role of miR-25 in HCC metastasis, and implicate the potential application of miR-25 in HCC therapy.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/antagonistas & inibidores , Animais , Carcinoma Hepatocelular/metabolismo , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Via de Sinalização Wnt , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/genética , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismo
14.
Oncol Rep ; 34(4): 1708-16, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26239364

RESUMO

Mammalian target of rapamycin (mTOR) is frequently upregulated in hepatocellular carcinoma (HCC). Blockage of mTOR was found to induce marked reduction in HCC growth in preclinical models. In the present study, we tested a novel mTOR inhibitor, Torin-2, for its antitumor efficacy in HCC cell lines Hep G2, SNU-182 and Hep 3B2.1-7. The HCC cell lines were cultured in vitro. These cells were treated with Torin-2. Cell apoptosis was evaluated by Annexin V staining. Cell proliferation and cell cycle progression were determined by Ki67 staining and propidium iodide staining, respectively. mTOR signaling, autophagy induction and expression of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) were assessed by western blot analysis. The UHRF1 mRNA level was determined by real-time PCR. We found that Torin-2 effectively suppressed the growth and survival of HCC cell lines, demonstrated by reduced proliferation and a high rate of apoptosis. Further study elucidated that in addition to blocking mTOR complex 1 (mTORC1)-associated cell cycle progression and induction of autophagy, Torin-2 downregulated transcription of UHRF1, an essential regulator of DNA methylation that is highly expressed in HCC cell lines. Consistently, the level of DNA (cytosine-5)-methyltransferase 1 (DNMT1) was higher after treatment of the HCC cell lines with Torin-2. The downregulation of UHRF1 by Torin-1 was partially due to a decrease in the UHRF1 mRNA level. Torin-2 effectively inhibited HCC cell proliferation through induction of autophagy. Torin­2-induced downregulation of UHRF1 expression may also contribute to its antitumor effect. Our research provides new clues regarding the antitumor effects of Torin-2 and sheds light on a novel therapeutic approach for HCC.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/biossíntese , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Naftiridinas/administração & dosagem , Autofagia/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , RNA Mensageiro/biossíntese , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Ubiquitina-Proteína Ligases
15.
Biomed Res Int ; 2015: 909870, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25710035

RESUMO

In order to investigate the potential of short antimicrobial peptides (AMPs) as alternative antibacterial agents during the treatment of peri-implantitis, the cytotoxic activity of three short AMPs, that is, Pac-525, KSL-W, and KSL, was determined using the MTT assay. The antimicrobial activity of these AMPs, ranging in concentration from 0.0039 mg/mL to 0.5 mg/mL, against the predominant planktonic pathogens, including Streptococcus sanguis, Fusobacterium nucleatum, and Porphyromonas gingivalis, involved in peri-implantitis was investigated. Furthermore, 2-day-old P. gingivalis biofilms cultured on titanium surfaces were treated with Pac-525 and subsequently observed and analysed using confocal laser scanning microscopy (CLSM). The average cell proliferation curve indicated that there was no cytotoxicity due to the three short AMPs. The minimum inhibitory concentration and minimum bactericidal concentration values of Pac-525 were 0.0625 mg/mL and 0.125 mg/mL, respectively, for P. gingivalis and 0.0078 mg/mL and 0.0156 mg/mL, respectively, for F. nucleatum. Using CLSM, we confirmed that compared to 0.1% chlorhexidine, 0.5 mg/mL of Pac-525 caused a significant decrease in biofilm thickness and a decline in the percentage of live bacteria. These data indicate that Pac-525 has unique properties that might make it suitable for the inhibition the growth of pathogenic bacteria around dental implants.


Assuntos
Antibacterianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Biofilmes/crescimento & desenvolvimento , Implantes Dentários/microbiologia , Porphyromonas gingivalis/fisiologia , Titânio , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biofilmes/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Materiais Dentários , Relação Dose-Resposta a Droga , Porphyromonas gingivalis/efeitos dos fármacos , Resultado do Tratamento
16.
PLoS One ; 8(8): e73158, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23991178

RESUMO

OBJECTIVE: This study aimed to investigate whether or not hypoxia-inducible factor-1α (HIF-1α) gene variants are associated with the susceptibility and clinical characteristics of lumbar disc degeneration (LDD). METHODS: We examined 320 patients with LDD and 447 gender- and age-matched control subjects. We also determined the HIF-1α gene variants, including C1772T (P582S) and G1790A (A588T) polymorphisms. RESULTS: Significant differences were observed in allelic and genotypic distributions of 1790 A > G polymorphisms between LDD cases and control subjects. Logistic regression revealed that 1790 AA genotypes indicated a protective effect against the development of LDD. The HIF-1α 1790 A > G polymorphisms also affected the severity of LDD as evaluated based on the modified Japanese Orthopedic Association (mJOA) scores. The 1790 AA genotype carriers exhibited significantly lower mJOA scores than AG and GG carriers. C1772T did not show any association with the risk and severity of LDD. CONCLUSION: Our study suggested that HIF-1α 1790 A > G polymorphisms may be used as a molecular marker to determine the susceptibility and severity of LDD.


Assuntos
Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Degeneração do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/genética , Polimorfismo Genético , Adulto , Alelos , Estudos de Casos e Controles , China , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Biomaterials ; 33(33): 8395-405, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22922021

RESUMO

Mechanical stimuli play important roles in regulating chondrogenic differentiation, but seldom studies have focused on when and how mechanical stimuli should be initiated. We have previously shown that Col2α1 mRNA was increased by delayed dynamic compressive stress initiated at the 8th day of chondrogenic culture. The current work is to further study the possibility of using delayed mechanical stress to relay chondrogenesis initiated by exogenous TGF-ß1. Mechanical stimulation was delivered from day 8 to day 14 of chondrogenic culture. It showed that delayed compressive stress not only stimulated gene expression and protein synthesis of chondrocyte-specific markers, but also stimulated the endogenous TGF-ß1 gene transcription, protein expression and the subsequent activation even when exogenous TGF-ß1 was discontinued. Furthermore, mechanical stress also promoted protein phosphorylation and nuclear translocation of Smad2/3, the TGF-ß1 downstream effectors. Inhibition TGF-ß with SB431542 significantly affected the stress-induced chondrogenic gene expression. In addition, phosphorylated-p38 and RhoB were upregulated by delayed loading in a TGF-ß-related manner. Phosphorylated-ERK1/2 and Wnt7a were also increased, but in a TGF-ß-independent way. It indicates that delayed compressive stress can be used as an effective substitute for TGF-ß1 supplement in inducing chondrogenic differentiation.


Assuntos
Condrócitos/citologia , Condrogênese/efeitos dos fármacos , Proteínas Smad Reguladas por Receptor/metabolismo , Estresse Mecânico , Fator de Crescimento Transformador beta1/farmacologia , Animais , Benzamidas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Dioxóis/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Coelhos , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad Reguladas por Receptor/genética , Alicerces Teciduais/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(4): 1094-7, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22715792

RESUMO

Thin films of cadmium sulfide (CdS) were prepared with ammonium chloride, cadmium chloride, potassium hydroxide and thiourea by chemical bath deposition (CBD). For comparison, CdS films were also deposited by radio frequency (RF) magnetron sputtering, using CdS and argon as a target and reactive gas, respectively. The films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and ultraviolet-visible spectroscopy. The results show that the CdS films prepared by the above two methods have (002) orientation, the CdS films deposited by RF magnetron sputtering are more compact and much smoother than those prepared by CBD, and have lager crystalline size of about 20-30 nm. The CdS films prepared by CBD have smaller crystalline size and more defects. The properties of CdS thin films prepared by RF magnetron sputtering are totally superior to those of CdS films by CBD, but the optical transmittance of CdS thin films at short wavelength is an exception. The energy gap of CdS films prepared by the two methods are all in the range of 2.3-2.5 eV.

19.
Anal Bioanal Chem ; 394(2): 617-23, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19247638

RESUMO

The conventional analytical HPLC was successfully developed for micro-column separation by using a simple eluate splitting system, a self-preparation of monolithic column and an on-capillary column detector in our laboratory. A typical polystyrene-based monolith was quickly prepared inside the fused-silica capillary, which in situ polymerization was carried out in 10 min by microwave irradiation. The reactant solution consisted of styrene (ST) as a functional monomer, divinylbenzene (DVB) as a cross-linking agent, toluene and isooctane as porogenic solvents, and azobisisobutyronitrile (AIBN) as an initiator. The monolith was proved to form in the center of the capillary and adhered to the column inner wall by the scanning electron micrograph. Its chromatographic behaviors were evaluated in detail by varying the flow rate and percentage of mobile phases, and under the optimal condition, baseline separation of the model analytes including thiourea, benzene, toluene, ethylbenzene was obtained with a highest theoretical plate number near 11,290 N/m by the developed capillary HPLC. Furthermore, the stability and porosity of the prepared monolith were systematically investigated by a simple flow method.

20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 26(2): 137-9, 143, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18605448

RESUMO

OBJECTIVE: To evaluate the chemical composition of the modified surface of fluoride ion-implanted titanium and assess the effect on the formation of focal adhesion plaque in vitro. METHODS: Pure commercial titanium discs were treated with fluoride ion implantation by plasma immersion ion implantation technique (PIII) and chemical composition and value of the surface modification layer were characterized by X-ray photoelectron spectrometer (XPS). In order to investigate the formation of focal adhesion plaque, MG-63 cells were seeded onto the surfaces of the modified Ti discs and quantified by morphometric analysis using an immunofluorescence microscope. RESULTS: The full range XPS spectra and fitting results indicated that the surface of fluoride ion-implanted titanium was the mixture of titanium dioxide and titanium trifluoride. Meanwhile, the quantity of focal adhesion plaque on fluoride ion-implanted titanium was more than that on the non-implanted titanium after 6 hours' cell culture. CONCLUSION: The XPS data revealed that the modified surface layer of fluoride ion-implanted titanium contained titanium dioxide and titanium trifluoride, which could enhance the formation of focal adhesion plaque.


Assuntos
Adesões Focais , Propriedades de Superfície , Fluoretos , Técnicas In Vitro , Próteses e Implantes , Titânio
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