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1.
Respir Res ; 21(1): 62, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111211

RESUMO

BACKGROUND: This study was to investigate of the mechanism by which histone deacetylase (HDAC) 8 inhibitor ameliorated airway hyperresponsiveness (AHR) and allergic airway inflammation. METHODS: Mice were sensitized and then treated with budesonide (BUD) or PCI-34051 (PCI) prior to exposing to normal saline (NS) or ovalbumin (OVA). The raw264.7 cells were treated with interleukin (IL)-4 and PCI or shRNA alone. Repetitive measurements of enhanced pause (Penh) were executed by increasing concentrations of acetyl-ß-methacholine chloride (0 - 50 mg/ml). Cells in bronchoalveolar lavage fluid (BALF) and pathological changes of lungs were examined, respectively. The expression levels of HDAC8, Galecitn (Gal)-3, CD68, CD86, CD163, Arg1 and NOS2 in lungs were measured. Co-regulation of HDAC8 and Gal-3 proteins was observed by immunofluorescence staining and co-immunoprecipitation assay (Co-IP). RESULTS: Significant increases in Penh and IL-4 level were detected with a large inflammatory infiltrate, comprised predominantly of macrophages and eosinophils, into the BALF in OVA-exposed lungs. HDAC8, Gal-3, CD68, CD86, CD163, Arg1 and NOS2 proteins were over-expressed with the significant changes in the Arg1 and NOS2 mRNA levels in the lungs and the IL-4-treated cells. PCI intervention obviously reduced the counts of CD163+ cells. Furthermore, Gal-3 knockdown suppressed Arg1 expression in the cells. Immunofluorescence staining displayed simultaneous changes in HDAC8 and Gal-3 expression in the investigated samples. Treatment with PCI resulted in synchronous reduction of HDAC8 and Gal-3 expression in the Co-IP complexes. CONCLUSIONS: The HDAC8 inhibitor ameliorates AHR and airway inflammation in animal model of allergic asthma through reducing HDAC8-Gal-3 interaction and M2 macrophage polarization.

2.
J Am Soc Cytopathol ; 8(5): 250-257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543224

RESUMO

INTRODUCTION: Cervical cancer rates in China remain high, with only limited opportunistic screening in urban centers and large mostly unscreened rural areas. Cervical cytology practices in China have been changing over the last decade with introduction of The Bethesda System reporting terminology, liquid-based cytology (LBC), and programs for cervical cytology screening of underserved rural populations. An effort was undertaken for the first time to collect nationwide data on cervical cytology laboratory practices in China, a possible first step toward increased standardization and potential development of nationwide cytology quality benchmarks. MATERIALS AND METHODS: Data on cervical cytology practices from 1572 laboratories operating in 26 nationwide Provisional Level Administrative Divisions was collected in an online survey approved through the Obstetrics and Gynecology Hospital of Fudan University in Shanghai. RESULTS: Over 90% of cervical cytology laboratories in China now solely use Bethesda System reporting terminology. LBC is now the most commonly utilized form of cervical cytology, with lower-cost Chinese-manufactured LBC formulations used in almost 70% of laboratories. Nationwide, significantly higher abnormal cytology rates were reported with LBC than with the conventional Papanicolaou smear (CPS); however, the CPS remains a useful low-cost alternative as China strives to extend cervical screening to large underserved rural areas. CONCLUSIONS: Abnormal cytology rates were not significantly different when different levels of hospitals were compared. The survey identified nationwide opportunities for cytology quality improvement, including low rates of reporting of unsatisfactory cases and low rates for atypical glandular cells.

3.
J Asthma ; : 1-8, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31514546

RESUMO

Purpose: The aim of this study was to investigate the efficacy and safety of tratinterol hydrochloride in bronchial asthma (BA) treatment. Methods: Patients enrolled in this study were distributed randomly into a treatment group (tratinterol hydrochloride) and an active control group (procaterol hydrochloride) and were treated for 2 weeks after running-in. The end points were changes in pulmonary function and clinical symptoms after administration. Safety indices were physical examinations, laboratory testing and spontaneous reporting. Findings: We enrolled 732 subjects, -365 in the treatment group and 367 in the active control group. Forced expiratory volume (FEV1), significantly increased in both group after treatment (P < 0.05). Least-squares (LS) means were -0.03/in the full-analysis set (FAS) and -0.02 in the per-protocol set (PPS) set, and 95% confidence intervals (CIs) for these sets were -0.09 to 0.03 and -0.08 to 0.04, respectively. Forced expiratory volume (FVC), morning peak expiratory flow (PEF) and asthma scores were significantly different with pretreatment (P < 0.05). There was no difference in asymptomatic days or frequency of relief medicine use (P > 0.05). No serious adverse events occurred. Implications: Tratinterol hydrochloride was effective, safe and not inferior to procaterol hydrochloride in treating BA.

4.
Genet Test Mol Biomarkers ; 23(5): 304-309, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30969151

RESUMO

Aims: Metastasis is a significant obstacle to curing esophageal squamous cell carcinoma (ESCC). The CCAAT/enhancer binding protein ß (C/EBPß) and matrix metalloproteinase 3 (MMP3) are thought to play key roles in cancer invasion and metastasis. In this study, we aimed to detect whether C/EBPß-mediated tumor invasion was dependent on MMP3. In addition, we determined whether C/EBPß upregulation was associated with MMP3 levels and metastatic status in patients with ESCC. Materials and Methods: A total of 126 patients with ESCC were recruited for this study. The mRNA and protein levels of C/EBPß and MMP3 in ESCC cell lines and specimens from ESCC patient were determined by reverse transcription-polymerase chain reaction and western blot, respectively. Tumor cell invasion was analyzed using an in vitro Matrigel Invasion Assay. The correlation between C/EBPß and MMP3 expression was determined by Pearson's correlation analysis. Results: Both mRNA and protein levels of MMP3 were upregulated by C/EBPß overexpression and downregulated by C/EBPß siRNA in KYSE150 cell cultures. The promotion of ESCC cell invasion through C/EBPß was inhibited by MMP3 siRNA. The level of C/EBPß was correlated with MMP3 and metastatic status in patients with ESCC. Conclusions: C/EBPß upregulation promoted tumor cell invasion in an MMP3-dependent manner in vitro and was associated with metastatic status in ESCC.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Carcinoma de Células Escamosas do Esôfago/genética , Metaloproteinase 3 da Matriz/fisiologia , Idoso , Proteína beta Intensificadora de Ligação a CCAAT/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , China , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Regulação para Cima
5.
Biochem Biophys Res Commun ; 509(2): 407-413, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30594391

RESUMO

BACKGROUND: The forkhead activin signal transducer 1 (FAST1) is involved in several oncogenic signaling pathways and its abnormal expression has been discovered in some cancers. Yet the role of FAST1 in colorectal cancer (CRC) remains largely unclear. Therefore, the goal of this study was to explore the function of FAST1 in CRC. METHODS: In this study, we analyzed FAST1 expression and its relationship with clinicopathological parameters and prognostic significance in CRC via immunohistochemistry analysis. The effects and mechanisms of FAST1 on cell proliferation, migration and invasion were explored in vitro and in vivo. RESULTS: We found that increased FAST1 as an independent prognostic factor was positively associated with TNM stage and pathological grade in CRC. FAST1 overexpression promoted the CRC cell proliferation, migration and invasion in vivo. Furthermore, mechanistic studies implicated that FAST1 enhanced the pulmonary metastasis of CRC cells through down-regulating E-cadherin levels. CONCLUSIONS: In summary, FAST1 was significantly associated with CRC progression and could serve as an independent prognostic factor. FAST1 may be potential therapeutic target for CRC patients.


Assuntos
Neoplasias Colorretais/genética , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Idoso , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Células HCT116 , Xenoenxertos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Transdução de Sinais , Análise de Sobrevida
6.
Nat Commun ; 9(1): 5326, 2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30552337

RESUMO

Alphaviruses are enveloped RNA viruses that contain several human pathogens. Due to intrinsic heterogeneity of alphavirus particles, a high resolution structure of the virion is currently lacking. Here we provide a 3.5 Å cryo-EM structure of Sindbis virus, using block based reconstruction method that overcomes the heterogeneity problem. Our structural analysis identifies a number of conserved residues that play pivotal roles in the virus life cycle. We identify a hydrophobic pocket in the subdomain D of E2 protein that is stabilized by an unknown pocket factor near the viral membrane. Residues in the pocket are conserved in different alphaviruses. The pocket strengthens the interactions of the E1/E2 heterodimer and may facilitate virus assembly. Our study provides structural insights into alphaviruses that may inform the design of drugs and vaccines.


Assuntos
Alphavirus/crescimento & desenvolvimento , Microscopia Crioeletrônica/métodos , Domínios e Motivos de Interação entre Proteínas , Montagem de Vírus , Internalização do Vírus , Animais , Cristalografia por Raios X , Estágios do Ciclo de Vida , Glicoproteínas de Membrana/química , Modelos Moleculares , Conformação Proteica , Vírus Sindbis/crescimento & desenvolvimento , Vírus Sindbis/ultraestrutura , Células Vero , Proteínas do Envelope Viral/química , Vírion/crescimento & desenvolvimento , Vírion/ultraestrutura
7.
Carcinogenesis ; 39(10): 1264-1273, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30107476

RESUMO

Caloric intake influences the onset of many diseases, including cancer. In particular, caloric restriction (CR) has been reported to suppress mammary tumorigenesis in various models. However, the underlying cancer preventive mechanisms have not been fully explored. To this end, we aimed to characterize the anticancer mechanisms of CR using MMTV-ErbB2 transgenic mice, a well-established spontaneous ErbB2-overexpressing mammary tumor model, by focusing on cellular and molecular changes in premalignant tissues. In MMTV-ErbB2 mice with 30% CR beginning at 8 weeks of age, mammary tumor development was dramatically inhibited, as exhibited by reduced tumor incidence and increased tumor latency. Morphogenic mammary gland analyses in 15- and 20-week-old mice indicated that CR significantly decreased mammary epithelial cell (MEC) density and proliferative index. To understand the underlying mechanisms, we analyzed the effects of CR on mammary stem/progenitor cells. Results from fluorescence-activated cell sorting analyses showed that CR modified mammary tissue hierarchy dynamics, as evidenced by decreased luminal cells (CD24highCD49flow), putative mammary reconstituting unit subpopulation (CD24highCD49fhigh) and luminal progenitor cells (CD61highCD49fhigh). Mammosphere and colony-forming cell assays demonstrated that CR significantly inhibited mammary stem cell self-renewal and progenitor cell numbers. Molecular analyses indicated that CR concurrently inhibited estrogen receptor (ER) and ErbB2 signaling. These molecular changes were accompanied by decreased mRNA levels of ER-targeted genes and epidermal growth factor receptor/ErbB2 family members and ligands, suggesting ER-ErbB2 signaling cross-talk. Collectively, our data demonstrate that CR significantly impacts ER and ErbB2 signaling, which induces profound changes in MEC reprogramming, and mammary stem/progenitor cell inhibition is a critical mechanism of CR-mediated breast cancer prevention.


Assuntos
Restrição Calórica/métodos , Carcinogênese/metabolismo , Neoplasias Mamárias Experimentais/dietoterapia , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Animais , Western Blotting , Proliferação de Células , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
8.
Helicobacter ; 23(3): e12486, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29656498

RESUMO

BACKGROUND: Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. MATERIALS AND METHODS: Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. RESULTS: In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress. CONCLUSIONS: These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori-induced gastric cancer.


Assuntos
Carcinogênese/patologia , Infecções por Helicobacter/patologia , Histonas/metabolismo , Fosforilação/fisiologia , Gastropatias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/metabolismo , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem/métodos , Estômago/patologia , Gastropatias/metabolismo , Gastropatias/microbiologia , Adulto Jovem
9.
J Asthma ; 55(10): 1079-1085, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29611766

RESUMO

BACKGROUND: The pathogenesis of asthma is complex and continues to be considered as a challenging subject. Some studies have shown that nerve growth factor (NGF) participates in the pathogenesis of asthma, but the mechanism of airway contraction caused by NGF is still unclear. OBJECTIVE: Our aim was to discuss the effect of anti-NGF antibody on RhoA expression, and further explore the role of NGF in airway hyperresponsiveness (AHR). METHODS: Thirty female BALB/c mice were divided into three groups randomly: control group (group C, n = 10), asthma group (group A, n = 10) and anti-NGF antibody intervention group (group N, n = 10). The asthmatic mice were stimulated by OVA suspension, the intervention mice were given nasal instillation of anti-NGF antibody before the stimulation. Airway responsiveness, eosinophils, IL-13, IFN-γ were measured. The protein expression and mRNA level of NGF and RhoA were detected by immunohistochemical and Real Time-PCR (RT-PCR) analyses. RESULTS: Airway responsiveness, eosinophils and IL-13 levels in group A were significantly increased compare with the other groups, and significantly decreased in group N than those in group A. IFN-γ level was significantly reduced in group A and increased in group N. Immunohistochemistry and RT-PCR analyses showed that the protein expression and mRNA level of NGF and RhoA were significantly increased in group A and significantly decreased in group N. CONCLUSION: NGF participates in the pathogenesis of asthma in mice. Anti-NGF antibody can inhibit airway inflammation and alleviate AHR by down-regulating the protein expression and mRNA level of RhoA.


Assuntos
Fator de Crescimento Neural/imunologia , Hipersensibilidade Respiratória/imunologia , Proteína rhoA de Ligação ao GTP/biossíntese , Animais , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Imuno-Histoquímica , Inflamação/imunologia , Interferon gama/biossíntese , Interleucina-13/biossíntese , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/fisiologia
10.
J Cancer Res Ther ; 14(1): 78-83, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29516964

RESUMO

Background: Glioblastoma (GBM) is one of the worst cancers with bad prognosis despite systemic chemotherapy and radiotherapy after surgery. Methods: In this study, 71 patients with GBM were enrolled and randomly assigned to two groups: Receiving radiotherapy with concomitant and adjuvant temozolomide (TMZ) (TMZ, standard therapy) after surgery, or receiving radiotherapy with concomitant and adjuvant local delivery of nimustine (ACNU) rendezvousing with oral TMZ (rendezvous therapy). In the follow-up of all patients and the progression-free survival (PFS), overall survival (OS), Karnofsky performance score (KPS) and toxicities were recorded. Results: For the whole cohort, the median OS was 18.0 months, and the median PFS was 7.8 months. A significantly longer OS was observed in patients received rendezvous therapy than those who receiving standard therapy (18.5 months vs. 16.0 months; P = 0.014), as well as PFS (8.8 months vs. 7.0 months; P = 0.008). The KPS ≥70 rates were 81.8%, 40.9%, 20.5% in 1, 2, and 3 years for the rendezvous therapy group, significantly superior to standard therapy group. The most common toxicities were tolerable gastrointestinal reaction, liver dysfunction, and hematological toxicities, which were relieved with symptomatic treatment. Grade 3 or 4 toxicity was documented in 8 (18.3%) patients in rendezvous therapy group, while it was observed in 6 (22.2%) patients in standard therapy group during whole treatment process. Conclusions: Compared to standard therapy, the antitumor effects of rendezvous therapy were more effective in GBM patients without increasing the toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Feminino , Seguimentos , Glioblastoma/diagnóstico , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nimustina/administração & dosagem , Modelos de Riscos Proporcionais , Qualidade de Vida , Radioterapia/efeitos adversos , Radioterapia/métodos , Temozolomida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Curr Med Res Opin ; 34(3): 423-433, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28945108

RESUMO

OBJECTIVE: To explore the association of asthma with serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglyceride. METHODS: PubMed, Cochrane, and Embase databases were systematically searched through November 2015 using the following search terms: dyslipidemia, HDL, LDL, triglyceride, cholesterol, and asthma. Eligible studies included randomized controlled trials (RCTs), retrospective, cohort, and cross-sectional studies. Sensitivity analysis and publication bias were performed. RESULTS: Twenty studies were included in the analysis, with a total 32,604 patients (3,458 in the asthma group and 29,146 in the control group). The pooled analysis found that the mean difference between groups was significantly higher in the asthma group for levels of LDL (6.026 mg/dL, 95% CI = 2.696-9.356, p < .001) and total cholesterol (8.161 mg/dL, 95% CI = 3.006-13.316, p = .002) compared with the control group. No association was observed between asthma and control groups for levels of HDL (mean difference = -0.728, 95% CI = -3.146-1.691, p = .555) or triglycerides (mean difference = 1.436, 95% CI = -2.768-5.640, p = .503). CONCLUSIONS: Levels of LDL and total cholesterol were higher in patients with asthma than non-asthmatic patients.


Assuntos
Asma/epidemiologia , Dislipidemias/epidemiologia , Lipídeos/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Prevalência , Triglicerídeos/sangue
13.
Exp Lung Res ; 43(9-10): 359-369, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29206498

RESUMO

AIM: The capability of reducing fibrotic and inflammatory responses in lung tissues represents a gold standard for evaluating the efficacy of therapeutic interventions for treating idiopathic pulmonary fibrosis (IPF). A wide variety of therapeutic strategies have been employed in clinic to treat PF, but limited success has been obtained. Apigenin (4, 5, 7-trihydroxyflavone) is a member of flavonoid family that exerts anti-inflammatory and anti-fibrosis effects. In this study, we explore the potential therapeutic effect of apigenin in lung fibrosis. MATERIALS AND METHODS: Apigenin was employed to treat IPF in a bleomycin-induced PF rat model. Apigenin was loaded onto a biodegradable polymer carrier (nanoparticle, NP) to improve its bio-solubility and bio-availability. The properties (e.g. size, apigenin loading and release profile) of the apigenin loaded polymer carrier were well-characterized. In vitro study was performed to assess the impact of apigenin on pulmonary cell viability, growth, as well as inflammatory and pro-fibrosis responses in pulmonary cells. The impact of apigenin on the production of inflammatory cytokines (e.g. TGF-ß, TNF-α) and pro-fibrosis factors in bronchoalveolar lavage fluid and pulmonary cells from lung tissues was also investigated. RESULTS: Our results showed, apigenin has anti-fibrosis effect by inhibition fibrosis related cytokines expression. And compared with apigenin in soluble form, the strategic release of apigenin is more effective in inhibiting pulmonary fibrosis and inflammation. CONCLUSION: Our finding suggested that apigenin loaded on polymeric carrier might be an effective treatment for pulmonary fibrosis patients.


Assuntos
Apigenina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Apigenina/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Portadores de Fármacos/química , Pulmão/metabolismo , Pulmão/patologia , Polímeros/uso terapêutico , Ratos
14.
Oncotarget ; 8(39): 64779-64792, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029391

RESUMO

Senescent stromal cells support the development of prostate cancer and are considered potential therapeutic targets. This research evaluated the regulatory effects of ginsenoside Rg3 on the senescence of prostatic stromal cells pre-incubated in medium supplemented with 0.5% fetal bovine serum. The results revealed that ginsenoside Rg3 decreased the number of stromal cells positively stained with a senescent cell marker (senescence-associated ß-galactosidase). Ginsenoside Rg3 also increased the viability of stromal cells and promoted cell cycle transition from G0/G1 to S phase, as well as inhibited the carcinoma-associated fibroblast-like phenotype in prostate stromal cells, through the up-regulation of smooth muscle cell markers SM22 and smooth muscle myosin heavy chain. Conditioned medium collected from stromal cells treated with ginsenoside Rg3 exhibited an attenuated effect on the promotion of prostate cancer cell migration compared with conditioned medium from stromal cells without Rg3 treatment. Down-regulation of interleukin 8 (IL-8) in a dose- and time-dependent manner was observed in ginsenoside Rg3-treated stromal cells, and over-expression or addition of IL-8 reversed the anti-senescence role of Rg3 in prostate stromal cells. Furthermore, ginsenoside Rg3 down-regulated IL-8 expression by decreasing the reactive oxygen species level in prostatic stromal cells and reducing the transcriptional activity of IL-8 promoter by damping the transcription factors C/EBP ß and p65 binding to IL-8 promoter. Our research revealed that ginsenoside Rg3 was able to inhibit prostate stromal cell senescence by down-regulating IL-8 expression. The results suggest a potential value for ginsenoside Rg3 in prostate cancer treatment through the targeting of pro-carcinogenic senescent stromal cells.

15.
Transl Oncol ; 10(6): 886-894, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28930698

RESUMO

OBJECTIVE: To compare 2D and 3D radiomics features prognostic performance differences in CT images of non-small cell lung cancer (NSCLC). METHOD: We enrolled 588 NSCLC patients from three independent cohorts. Two sets of 463 patients from two different institutes were used as the training cohort. The remaining cohort with 125 patients was set as the validation cohort. A total of 1014 radiomics features (507 2D features and 507 3D features correspondingly) were assessed. Based on the dichotomized survival data, 2D and 3D radiomics indicators were calculated for each patient by trained classifiers. We used the area under the receiver operating characteristic curve (AUC) to assess the prediction performance of trained classifiers (the support vector machine and logistic regression). Kaplan-Meier and Cox hazard survival analyses were also employed. Harrell's concordance index (C-Index) and Akaike's information criteria (AIC) were applied to assess the trained models. RESULTS: Radiomics indicators were built and compared by AUCs. In the training cohort, 2D_AUC=0.653, 3D_AUC=0.671. In the validation cohort, 2D_AUC=0.755, 3D_AUC=0.663. Both 2D and 3D trained indicators achieved significant results (P<.05) in the Kaplan-Meier analysis and Cox regression. In the validation cohort, 2D Cox model had a C-Index=0.683 and AIC=789.047; 3D Cox model obtained a C-Index=0.632 and AIC=799.409. CONCLUSION: Both 2D and 3D CT radiomics features have a certain prognostic ability in NSCLC, but 2D features showed better performance in our tests. Considering the cost of the radiomics features calculation, 2D features are more recommended for use in the current study.

16.
Am J Transl Res ; 9(1): 103-114, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28123637

RESUMO

miR-34a is an important molecule that can inhibit the tumor growth. This study aimed to investigate the functional role of miR-34a in hepatocellular carcinoma (HCC) and explore the interaction between miR-34a and histone deacetylase 1 (HDAC1). RT-qPCR was employed to detect the mRNA expression of miR-34a and HDAC1 in 60 HCC tissues. Results showed miR-34a expression in HCC tissues was significantly lower than in normal tissues (P<0.05), but HDAC1 expression in HCC tissues was markedly higher than in normal tissues (P<0.05). In addition, miR-34a expression was negatively related to HDAC1 expression. miR-34a mimic was transfected into HCC cell lines (HepB3 and HepG2). CCK8 assay, colony formation assay and flow cytometry showed miR-34a over-expression could inhibit the proliferation of HCC cells and induce their apoptosis. Western blotting indicated miR-34a over-expression down-regulated the expression of Bcl-2, procaspase-3, procaspase-9 and c-Myc, but up-regulate p21 expression. Bioinformatics analysis indicated HDAC1 was a target gene of miR-34a. Dual Luciferase Reporter Gene Assay and retrieval assay showed miR-34a could act at the 3'UTR of HDAC1 gene to regulate its expression. Thus, miR-34a may inhibit the proliferation of HCC cells and induce their apoptosis via regulating HDAC1 expression. Our findings provide evidence for the diagnosis and therapeutic target of HCC.

17.
Oncotarget ; 8(4): 5834-5842, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-27992380

RESUMO

Using noninvasive magnetic resonance imaging techniques to accurately evaluate the grading and cellularity of gliomas is beneficial for improving the patient outcomes. Amide proton transfer imaging is a noninvasive molecular magnetic resonance imaging technique based on chemical exchange saturation transfer mechanism that detects endogenous mobile proteins and peptides in biological tissues. Between August 2012 and November 2015, a total number of 44 patients with pathologically proven gliomas were included in this study. We compared the capability of amide proton transfer magnetic resonance imaging with that of noninvasive diffusion-weighted imaging and noninvasive 3-dimensional pseudo-continuous arterial spin imaging in evaluating the grading and cellularity of gliomas. Our results reveal that amide proton transfer magnetic resonance imaging is a superior imaging technique to diffusion-weighted imaging and 3-dimensional pseudo-continuous arterial spin imaging in the grading of gliomas. In addition, our results showed that the Ki-67 index correlated better with the amide proton transfer-weighted signal intensity than with the apparent diffusion coefficient value or the cerebral blood flow value in the gliomas. Amide proton transfer magnetic resonance imaging is a promising method for predicting the grading and cellularity of gliomas.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/patologia , Adulto , Idoso , Neoplasias Encefálicas/metabolismo , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Glioma/metabolismo , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Antígeno Ki-67/metabolismo , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores
18.
Clin Ther ; 38(12): 2622-2627.e1, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27913032

RESUMO

PURPOSE: To evaluate and contrast the therapeutic effect and safety of fluticasone aerosol combined with theophylline tablets in patients with moderate to severe asthma, compared with salmeterol/fluticasone propionate aerosol. METHODS: After a screening period, patients meeting the inclusion criteria were randomly assigned to the experiment group (fluticasone aerosol combined with theophylline tablets) or the control group (salmeterol/fluticasone aerosol combined with placebo tablets) for 12 weeks of treatment. The main outcome measurements were forced expiratory volume in 1 second and fractional concentration of exhaled nitric oxide value, whereas the secondary measures were forced vital capacity, peak expiratory flow value, and Asthma Control Test/Asthma Quality of Life Questionnaire score. FINDINGS: Forty-four cases completed the course, with 23 cases in the experiment group and 21 cases in the control group. The forced expiratory volume in 1 second values of both groups were significantly improved from before (P < 0.05). The fractional concentration of exhaled nitric oxide values of both groups were significantly decreased from before (P < 0.05). The secondary outcome measurements after treatment achieved obvious improvement from baseline (P < 0.05) in both. There was no significant difference between the 2 groups in all measurements. In addition, the blood biochemistry results, ECG results, and vital signs of both groups had no significant abnormality. IMPLICATIONS: There was no significant difference in therapeutic effect and safety between the 2 groups in treating patients with moderate to severe persistent asthma, which suggests that fluticasone aerosol combined with theophylline tablets is worth considering for use in primary hospitals or for low-income populations.


Assuntos
Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Albuterol/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Fluticasona/uso terapêutico , Teofilina/uso terapêutico , Adulto , Aerossóis , Idoso , Asma/fisiopatologia , Asma/psicologia , Preparações de Ação Retardada , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
19.
Int Immunopharmacol ; 39: 229-235, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27494686

RESUMO

Sepsis is a serious disease that leads to severe inflammation, dysregulation of immune system, multi-organ failure and death. Innate response activator (IRA) B cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF), protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti-inflammatory and immunoregulatory effects, and it has been reported that LXA4 receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis. We found that LXA4 significantly promoted the expansion of splenic IRA B cells and increased GM-CSF expression in splenic B cells with LPS stimulation. After splenectomy, LXA4 treatment did not change the serum or peritoneal IL-1ß, IL-6 and TNF-α levels in LPS-induced sepsis. LXA4 accelerated the migration of peritoneal B cells to spleen for their differentiation into IRA B cells, whereas this effect was independent of peritoneal macrophage. Furthermore, LXA4 enhanced the phosphorylation level of signal transducer and activator of transcription 5 (STAT5) in splenic B cells. These results suggest that LXA4 protects against LPS-induced sepsis by promoting the generation and migration of splenic IRA B cells, and the underlying molecular mechanism may be related to STAT5 activation. It might provide new insights and therapeutic approaches for treating sepsis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Linfócitos B/efeitos dos fármacos , Imunidade Inata , Lipoxinas/uso terapêutico , Fator de Transcrição STAT5/metabolismo , Sepse/tratamento farmacológico , Animais , Linfócitos B/imunologia , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Sepse/induzido quimicamente
20.
Inflamm Res ; 65(12): 995-1008, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27565183

RESUMO

OBJECTIVE AND DESIGN: To investigate the therapeutic effects of various HDAC inhibitors on the development of chronic allergic airway disease in mice with airway inflammation, airway remodeling, and airway hyperresponsiveness. SUBJECTS: Wild-type BALB/C mice (N = 72). TREATMENT: Tubastatin A HCl [TSA, a selective histone deacetylase 6 (HDAC6) inhibitor], PCI-34051 (a selective HDAC8 inhibitor), and givinostat (a broad-spectrum HDAC inhibitor that inhibits class I and class II HDACs and several pro-inflammatory cytokines). METHODS: Mice were divided into six groups: control, asthma, dexamethasone (positive control), TSA, PCI-34051, and givinostat (n = 12 per group). Twenty-four hours after OVA nebulization, airway hyperresponsiveness, inflammation, and remodeling were assessed. RESULTS: The chronic asthma mouse model produced typical airway inflammation, airway remodeling, and airway hyperresponsiveness. Administration of PCI-34051 and dexamethasone reduced the eosinophilic inflammation and airway hyperresponsiveness in asthma to reduce the airway remodeling. Treatment with Tubastatin A HCl reduced airway inflammation and was associated with decreased IL-4, IL-5 and total inflammatory cell count, as well as goblet cell metaplasia and subepithelial fibrosis; however, this outcome was not as effective as that with dexamethasone. TGF-ß1 expression in the cytoplasm of airway epithelium of mice in the Tubastatin A HCl group was reduced and expression of α-SMA in the airway smooth muscle was also decreased. CONCLUSIONS: The results suggested that treatment with HDAC inhibitors can reduce airway inflammation, airway remodeling, and airway hyperresponsiveness in chronic allergic airway disease in mice.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Actinas/metabolismo , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Antiasmáticos/farmacologia , Asma/metabolismo , Asma/patologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/tratamento farmacológico , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Colágeno/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator de Crescimento Transformador beta1/metabolismo
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