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1.
J Vis Exp ; (155)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32065164

RESUMO

Rheumatoid arthritis (RA) is a complex chronic inflammatory autoimmune disease. The pathogenesis of the disease is related to invariant natural killer T (iNKT) cells. Patients with active RA present fewer iNKT cells, defective cell function, and excessive polarization of Th1. In this study, an RA animal model was established using a mixture of hGPI325-339 and hGPI469-483 peptides. The iNKT cells were obtained by in vivo induction and in vitro purification, followed by infusion into RA mice for adoptive immunotherapy. The in vivo imaging system (IVIS) tracking revealed that iNKT cells were mainly distributed in the spleen and liver. On day 12 after cell therapy, the disease progression slowed down significantly, the clinical symptoms were alleviated, the abundance of iNKT cells in the thymus increased, the proportion of iNKT1 in the thymus decreased, and the levels of TNF-α, IFN-γ, and IL-6 in the serum decreased. Adoptive immunotherapy of iNKT cells restored the balance of immune cells and corrected the excessive inflammation of the body.

2.
Int Immunopharmacol ; 77: 105948, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629216

RESUMO

OBJECTIVE: The role of iNKT cells was investigated in chronic adipose tissue inflammation in obese mice after administration of α-GalCer in different pathways. METHODS: C57BL/6J mice were fed high-fat diet (HFD) for 12 weeks to establish the obese mouse model. The pathology of adipose tissue was observed by H&E staining. The rates of iNKT cells, macrophages and cell subsets in adipose tissue were detected by FCM. Cytokine levels in serum and adipose tissue lymphocyte-stimulated supernatants were assessed with the CBA kit. The expression levels of related transcription factor in adipose tissue were detected by Western blot. RESULTS: The proportions of iNKT cells, iNKT10 cells and M2 macrophages were decreased, while those of iNKT1 and M1 macrophages were increased in adipose tissue of HFD-fed mice. The expression levels of the related transcriptional proteins E4BP4 and Arg-1 were decreased while iNOS expression was increased in adipose tissue. Administration of α-GalCer by subcutaneous injection resulted in increased rates of iNKT10 cells and M2 macrophages, and decreased amounts of M1 macrophages in adipose tissue of HFD-fed mice. The expression of E4BP4 and Arg-1 were up-regulated, but iNOS was down-regulated. Meanwhile, infiltration of inflammatory cells into adipose tissue was further reduced. CONCLUSION: The imbalance between the proportions of iNKT1 and iNKT10 cells may be involved in the development of chronic inflammation in obese adipose tissue. Administration of α-GalCer by subcutaneous injection in HFD-fed mice activates adipose tissue iNKT10 cells, which promote M2 macrophage polarization and improve chronic inflammation in obese adipose tissue.

3.
Toxicology ; 428: 152307, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589899

RESUMO

Hepatic sinusoidal obstruction syndrome (HSOS) is a life-threatening liver disease caused by the damage to liver sinusoidal endothelial cells (LSECs). Liquiritigenin and liquiritin are two main compounds in Glycyrrhizae Radix et Rhizoma (Gan-cao). Our previous study has shown that both liquiritigenin and liquiritin alleviated monocrotaline (MCT)-induced HSOS in rats via inducing the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signaling pathway. This study aims to further investigate whether inhibiting liver inflammatory injury also contributed to the liquiritigenin and liquiritin-provided alleviation on MCT-induced HSOS. The results of serum alanine/aspartate aminotransferases (ALT/AST) activities and total bilirubin (TBil) amount, liver histological evaluation, scanning electron microscope observation and hepatic metalloproteinase-9 (MMP9) expression showed that liquiritigenin and liquiritin both alleviated MCT-induced HSOS in rats. Liquiritigenin and liquiritin reduced the increased liver myeloperoxidase (MPO) activity, mRNA expression of pro-inflammatory factors, hepatic infiltration of immune cells, hepatic toll-like receptor 4 (TLR4) expression and nuclear factor κB (NFκB) nuclear accumulation induced by MCT in rats. Furthermore, liquiritigenin and liquiritin attenuated MCT-induced liver mitochondrial injury, increased the decreased Lon protein expression and reduced the release of heat shock protein 60 (HSP60). Moreover, liquiritigenin and liquiritin also reduced NFκB nuclear accumulation and decreased the elevated cellular mRNA expression of NFκB-downstream pro-inflammatory cytokines induced by HSP60 in macrophage RAW264.7 cells. In conclusion, our study revealed that both liquiritigenin and liquiritin alleviated MCT-induced HSOS by inhibiting hepatic inflammatory responses triggered by HSP60.

4.
ACS Appl Mater Interfaces ; 11(45): 42708-42714, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31625728

RESUMO

Reliability and lifespan of highly miniaturized and integrated devices will be effectively improved if excessive accumulated heat can be quickly transported to heat sinks. In this study, both molecular dynamics (MD) simulations and experiments were performed to demonstrate that self-assembled monolayers (SAMs) have high potential in interfacial thermal management and can enhance thermal transport across the polystyrene (PS)/silicon (Si) interface, modeling the common polymer/semiconductor interfaces in actual devices. The influence of packing density and alkyl-chain length of SAMs is investigated. First, MD simulations show that the interfacial thermal transport efficiency of SAM is higher with high packing density. The interfacial thermal conductance (ITC) between PS and Si can be improved up to 127 ± 9 MW m-2 K-1, close to the ITC across the metal and semiconductor interface. At moderate packing density, the SAMs with less than eight carbon atoms in the alkyl chain show superior improvements over those with more carbons because of the assembled structure variation. Second, the time-domain thermoreflectance technique was employed to characterize the ITCs of a bunch of Al/PS/SAM/Si samples. C6-SAM enhances the ITC by fivefolds, from 11 ± 1 to 56 ± 17 MW m-2 K-1. The interfacial thermal management efficiency will weaken when the alkyl chain exceeds eight carbon atoms, which agrees with the ITC trend from MD simulations at moderate packing density. The relationship between the SAM morphology and interfacial thermal management efficiency is also discussed in detail. This study demonstrates the feasibility of molecular-level design for interfacial thermal management from both the theoretical calculation and experiment and may provide a new idea for improving the heat dissipation efficiency of microdevices.

5.
Immunogenetics ; 71(7): 489-499, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31297569

RESUMO

Epigenetic modifications have been shown to be important for immune cell differentiation by regulating gene transcription. However, the role and mechanism of histone methylation in the development and differentiation of iNKT cells in rheumatoid arthritis (RA) mice have yet to be deciphered. The DBA/1 mouse RA model was established by using a modified GPI mixed peptide. We demonstrated that total peripheral blood, thymus, and spleen iNKT cells in RA mice decreased significantly, while iNKT1 in the thymus and spleen was increased significantly. PLZF protein and PLZF mRNA levels were significantly decreased in thymus DP T cells, while T-bet protein and mRNA were significantly increased in thymus iNKT cells. We found a marked accumulation in H3K27me3 around the promoter regions of the signature gene Zbtb16 in RA mice thymus DP T cells, and an accumulation of H3K4me3 around the promoters of the Tbx21 gene in iNKT cells. The expression levels of UTX in the thymus of RA mice were significantly reduced. The changes in the above indicators were particularly significant in the progressive phase of inflammation (11 days after modeling) and the peak phase of inflammation (14 days after modeling) in RA mice. Developmental and differentiation defects of iNKT cells in RA mice were associated with abnormal methylation levels (H3K27me3 and H3K4me3) in the promoters of key genes Zbtb16 (encoding PLZF) and Tbx21 (encoding T-bet). Decreased UTX of thymus histone demethylase levels resulted in the accumulation of H3K27me3 modification.


Assuntos
Artrite Reumatoide/patologia , Lisina/metabolismo , Células T Matadoras Naturais/patologia , Regiões Promotoras Genéticas , Timo/fisiologia , Animais , Artrite Experimental/patologia , Diferenciação Celular , Epigênese Genética , Regulação da Expressão Gênica , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Metilação , Camundongos Endogâmicos DBA , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Baço/patologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo
6.
Int Immunopharmacol ; 74: 105727, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284229

RESUMO

The existence of association between the subpopulation of iNKT cells with different functions and nonalcoholic fatty liver disease has not been confirmed. To investigative the role of iNKT cells in the pathogenesis of nonalcoholic fatty liver disease, we established a non-alcoholic fatty liver model by feeding C57BL/6J mice for 12 weeks with a high-fat diet and injecting α-GalCer through different routes to activate hepatic iNKT cells. The liver of the mice fed a high-fat diet (HFD) had severe hepatic steatosis appearance, elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines in the liver, and high serum levels of TC, LDL, HDL, and ALT. Our results showed that the percentage of iNKT cells in the liver of the HFD-fed mice was lower than that of the control mice. The expression levels of the related transcription factor of T-bet increased but that of GATA-3 decreased in the HFD-fed mice. The administration of α-GalCer by intraperitoneal injection resulted in increasing of hepatic iNKT and iNKT2 cells but decreasing of hepatic iNKT1 cells, and the expression of GATA-3 and anti-inflammatory cytokine (IL-4) was increased in the liver, and hepatic steatosis was ameliorated in the HFD-fed mice. The administration of α-GalCer by subcutaneous injection resulted in a decrease in hepatic iNKT and iNKT2 and an augmentation of hepatic iNKT1 cells. However, hepatic steatosis was not significantly improved. We concluded that the intraperitoneal injection with α-GalCer effectively improved hepatic steatosis, according to increasing the number of hepatic iNKT2 cells. The precise mechanism requires further exploration.

7.
J Nanosci Nanotechnol ; 19(12): 7689-7695, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196276

RESUMO

Fabrication of p-n heterojunction materials is an efficient strategy for improving the photocatalytic activity by suppressing the recombination of photogenerated electrons and holes. In this study, a p-n heterojunction consisting of Cu2O and In2O3 was synthesized using the hydrothermal in situ deposition method. The Cu2O/In2O3 hybrid exhibited enhanced performance in the photocatalytic hydrogen evolution reaction and degradation of organic pollutants compared with pure Cu2O and In2O3. The sensitization of In2O3 by Cu2O considerably enhanced the light response of the Cu2O/In2O3 hybrid, and the close contact between In2O3 and Cu2O led to the generation of the p-n heterojunction. The photoelectrochemical properties test proved that the successful fabrication of the p-n heterojunction in the Cu2O/In2O3 hybrid promoted the transfer of photoinduced electrons and holes and inhibited the recombination of photogenerated carriers efficiently. The present strategy provides an efficient approach to improve the performance of photocatalysts through the fabrication of p-n heterojunctions.

8.
Eur J Pharmacol ; 856: 172421, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31136760

RESUMO

Cyclophosphamide (CPA) is a chemotherapeutic drug widely used in the treatment of breast cancer or leukemia in clinic. However, CPA was reported to have hepatotoxicity. This study aims to observe the engaged mechanism of CPA-induced liver injury in mice and the protection of liquiritin (LQ) and liquiritigenin (LG). Liver sinusoidal endothelial injury induced by CPA (20, 40 mg/kg) in mice was evidenced by the elevated hepatic metalloproteinase-9 (MMP-9) expression, and the results from liver histological evaluation and scanning electron microscope observation. CPA increased hepatic infiltration of neutrophils, liver myeloperoxidase (MPO) activity, serum interleukin-6 (IL-6) content, hepatic IL-6 mRNA expression, toll-like receptor-4 (TLR4) expression and nuclear factor κB (NFκB) activation in mice. Elevated serum contents of damage associated molecular patterns (DAMPs) including high mobility group box 1 (HMGB1), heat shock protein 60 (HSP60) and glucose-regulated protein 94 (Grp94) were found in mice treated with CPA. Liver sinusoidal endothelial injury and inflammation induced by CPA were diminished in TLR4 knock-out mice. LG and LQ (40, 80 mg/kg) both ameliorated liver sinusoidal endothelial injury, and reduced the increased hepatic infiltration of neutrophils, MPO activity, hepatic IL-6 mRNA expression and NFκB activation induced by CPA. In summary, these results indicate that TLR4-NFκB-mediated inflammatory injury initiated by DAMPs was critically involved in CPA-induced hepatotoxicity. LG and LQ alleviated CPA-induced liver sinusoidal endothelial injury and inflammatory injury in mice.


Assuntos
Alarminas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclofosfamida/efeitos adversos , Flavanonas/farmacologia , Glucosídeos/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
9.
Appl Biochem Biotechnol ; 189(1): 193-205, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30969398

RESUMO

Utilization of low-cost raw materials for the bio-based chemical production, such as carotenoids, by the co-culture of Rhodotorula glutinis and Chlorella vulgaris has recently become an attractive option. In this study, the primary nutrients of starch wastewater were analyzed, which were used for carotenoid production by the co-culture strategy in a 5-L fermenter around 4000 Lux light intensity. Synergistic effect of gas utilization revealed that the two species could build up the beneficial balance on mutualism. The maximum carotenoid productivity and COD removal efficiency were 12.34 mg/L and 79.6%, respectively, which were higher than those of monoculture yeast (8.31 mg/L and 54.1%). The organic acids, amino acids, and sugar removal efficiencies were increased by 85%, 31%, and 44%, respectively, and more than three kinds of carotenoids were identified compared with those of monoculture yeast. The results demonstrated that the co-culture strategy of two different nutritional microorganisms could significantly improve carotenoid productivity and COD removal efficiency.


Assuntos
Análise da Demanda Biológica de Oxigênio , Carotenoides/isolamento & purificação , Chlorella vulgaris/metabolismo , Rhodotorula/metabolismo , Águas Residuárias , Técnicas de Cocultura
10.
Antioxid Redox Signal ; 30(11): 1432-1449, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29869529

RESUMO

AIMS: Pharmacological treatments for Alzheimer's disease (AD) have not resulted in desirable clinical efficacy over 100 years. Hydrogen peroxide (H2O2), a reactive and the most stable compound of reactive oxygen species, contributes to oxidative stress in AD patients. In this study, we designed a medical device to emit red light at 630 ± 15 nm from a light-emitting diode (LED-RL) and investigated whether the LED-RL reduces brain H2O2 levels and improves memory in senescence-accelerated prone 8 mouse (SAMP8) model of age-related dementia. RESULTS: We found that age-associated H2O2 directly inhibited formaldehyde dehydrogenase (FDH). FDH inactivity and semicarbazide-sensitive amine oxidase (SSAO) disorder resulted in endogenous formaldehyde (FA) accumulation. Unexpectedly, excess FA, in turn, caused acetylcholine (Ach) deficiency by inhibiting choline acetyltransferase (ChAT) activity in vitro and in vivo. Interestingly, the 630 nm red light can penetrate the skull and the abdomen with light penetration rates of ∼49% and ∼43%, respectively. Illumination with LED-RL markedly activated both catalase and FDH in the brains, cultured cells, and purified protein solutions, all reduced brain H2O2 and FA levels and restored brain Ach contents. Consequently, LED-RL not only prevented early-stage memory decline but also rescued late-stage memory deficits in SAMP8 mice. INNOVATION: We developed a phototherapeutic device with 630 nm red light, and this LED-RL reduced brain H2O2 levels and reversed age-related memory disorders. CONCLUSIONS: The phototherapy of LED-RL has low photo toxicity and high rate of tissue penetration and noninvasively reverses aging-associated cognitive decline. This finding opens a promising opportunity to translate LED-RL into clinical treatment for patients with dementia. Antioxid. Redox Signal. 00, 000-000.

11.
R Soc Open Sci ; 5(10): 180951, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30473840

RESUMO

Aiming at the problem of the fatigue life prediction of rubber under the influence of temperature, the effects of thermal ageing and fatigue damage on the fatigue life of rubber under the influence of temperature are analysed and a fatigue life prediction model is established by selecting strain energy as a fatigue damage parameter based on the uniaxial tensile data of dumbbell rubber specimens at different temperatures. Firstly, the strain energy of rubber specimens at different temperatures is obtained by the Yeoh model, and the relationship between it and rubber fatigue life at different temperatures is fitted by the least-square method. Secondly, the function formula of temperature and model parameters is obtained by the least-square polynomial fitting. Finally, another group of rubber specimens is tested at different temperatures and the fatigue characteristics are predicted by using the proposed prediction model under the influence of temperature, and the results are compared with the measured results. The results show that the predicted value of the model is consistent with the measured value and the average relative error is less than 22.26%, which indicates that the model can predict the fatigue life of this kind of rubber specimen at different temperatures. What's more, the model proposed in this study has a high practical value in engineering practice of rubber fatigue life prediction at different temperatures.

12.
J Alzheimers Dis ; 64(4): 1347-1358, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29991131

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia, affecting millions of older people worldwide. However, pharmacological therapies have not achieved desirable clinical efficacy in the past decades. Non-pharmacological therapies have been receiving increased attention to treat dementia in recent years. OBJECTIVE: This study explores the effects of music therapy on cognitive function and mental wellbeing of patients with AD. METHODS: A total number of 298 AD patients with mild, moderate, or severe dementia participated in the study. The participants with each grade of severity were randomly divided into three groups, which were a singing group, a lyric reading group, and a control group. These three groups received different interventions for three months. All participants underwent a series of tests on cognitive functions, neuropsychological symptoms, and activities of daily living at baseline, three months, and six months. RESULTS: The analysis shows that music therapy is more effective for improving verbal fluency and for alleviating the psychiatric symptoms and caregiver distress than lyrics reading in patients with AD. Stratified analysis shows that music therapy is effective for enhancing memory and language ability in patients with mild AD and reducing the psychiatric symptoms and caregiver distress in patients with moderate or severe AD. However, no significant effect was found for activities of daily living in patients with mild, moderate, or severe AD. CONCLUSION: This study suggests that music therapy is effective in enhancing cognitive function and mental wellbeing and can be recommended as an alternative approach to manage AD associated symptoms.


Assuntos
Atividades Cotidianas , Doença de Alzheimer , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/reabilitação , Musicoterapia/métodos , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Doença de Alzheimer/reabilitação , Feminino , Humanos , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento , Aprendizagem Verbal
13.
J Clin Lab Anal ; 32(4): e22344, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29105177

RESUMO

BACKGROUND: As a result of physiological and metabolic changes during pregnancy, thyroid hormones can be affected significantly throughout entire three trimesters. According to the guidelines published by American Thyroid Association in 2017, it is strongly recommended to establish population-based trimester-specific and assay method-specific reference intervals (RIs) using local population. METHODS: A total of 1209 pregnant women without personal or family history of thyroid disease were recruited from July 2015 to April 2017 at Beijing Obstetrics and Gynecology Hospital. Those initially selected patients were further tested for TSH, FT4 and thyroid peroxidase antibody (aTPO), performed on the chemiluminescent platform Siemens ADVIA Centaur® XP. Only patients tested negative for aTPO were included in reference interval establishment. RIs for both TSH and FT4 were determined as 2.5th percentile to 97.5th percentile on the data distribution. RESULTS: The TSH and FT4 trimester-specific RIs were as follows: 0.59-3.54 mIU/L, 11.8-18.4 pmol/L (n = 188, 1st trimester); 0.80-4.46 mIU/L, 11.6-17.4 pmol/L (n = 133, 2nd trimester); 0.72-4.19 mIU/L, 9.7-15.1 pmol/L (n = 157, 3rd trimester). The RIs of TSH and FT4 determined by Hoffmann method for first trimester outpatient pregnant women were 0.33-3.96 mIU/L (n = 9924) and 11.7-17.5 pmol/L (n = 10039), respectively. CONCLUSION: Trimester-specific thyroid function tests RIs are distinct from those provided by assay manufacturers. The RIs determined by direct sampling and Hoffmann indirect calculation showed no statistical difference.


Assuntos
Trimestres da Gravidez/sangue , Tireotropina/sangue , Tiroxina/sangue , Adulto , Estudos de Coortes , Feminino , Humanos , Gravidez , Valores de Referência , Testes de Função Tireóidea , Adulto Jovem
14.
Head Neck ; 40(3): 498-511, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29240278

RESUMO

BACKGROUND: Thirty-day hospital readmissions have become a measure of quality of care. Many readmissions enter through the emergency department. The purposes of this study were to determine the rate, risk factors, and costs of 30-day returns to the emergency department (30dEDRs) after head and neck surgery. METHODS: All adult patients undergoing head and neck surgery at the University of Florida from 2012 to 2014 were reviewed. Univariate and multivariate logistic regression analyses were performed to identify risk factors for 30dEDRs. RESULTS: We found 1065 patients who underwent 1173 procedures. There were 88 cases (7.5%) that resulted in 30dEDRs and 55 patients (4.7%) who had 30-day unplanned readmissions (30dURs). Significant predictors of 30dEDRs included: smoking; hypothyroidism; and intensive care unit (ICU) stays. Significant predictors of readmission from an emergency department visit were Charlson Comorbidity Index (CCI) and cancer stage. Total costs of 30dEDRs and any subsequent readmissions topped $500 000. CONCLUSION: The rate of 30dEDRs after head and neck surgery is low; however, these visits increase the hospitals' financial burden as well as patient morbidity. Predictors of 30dEDRs may be utilized to formulate preventative measures.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Neoplasias de Cabeça e Pescoço/cirurgia , Custos de Cuidados de Saúde/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Serviço Hospitalar de Emergência/economia , Feminino , Florida , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/economia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
15.
Biotechnol Lett ; 39(12): 1827-1834, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28861760

RESUMO

OBJECTIVE: To evaluate the role and the molecular mechanism of miR-30d in non-small cell lung cancer (NSCLC). RESULTS: qRT-PCR was used to detect miR-30d expression in NSCLC tissues and cell lines. miR-30d was frequently down-regulated in NSCLC and its expression was associated with clinicopathological features of NSCLCC patients. Over-expression of miR-30d notably inhibited cell migration and invasion in NSCLC cell lines. miR-30d could negatively regulate Nuclear factor I B (NFIB) by directly targeting its 3'-UTR, which was confirmed by luciferase assay. NFIB also reversed miR-30d-mediated suppression on the migration and invasion in NSCLC cell lines. CONCLUSION: miR-30d suppressed cell migration and invasion by directly targeting NFIB in NSCLC, and NFIB could partially abrogated the inhibition of biological functions by miR-30d.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Fatores de Transcrição NFI/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular , Linhagem Celular Tumoral , Regulação para Baixo/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética
16.
ACS Appl Mater Interfaces ; 9(30): 25114-25127, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28675030

RESUMO

Well-designed gold nanoclusters-indocyanine green nanoprobes (Au NCs-INPs) have been developed by the conjugation of Au NC assemblies with indocyanine green (ICG) for the therapeutic real-time monitoring based on fluorescence resonance energy transfer (FRET). The synthesized Au NCs-INPs demonstrated the improved cellular uptake and effective tumor targeting because of the enhanced permeability and retention effect and the gp60-mediated secreted protein acidic and rich in cysteine combined transport pathway, suggesting excellent dual-modal near-infrared fluorescence and photoacoustic imaging. Moreover, the simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT) of Au NCs-INPs exhibited higher cancer cell killing and tumor removal efficiency than those of PDT or PTT alone. More importantly, a promising therapeutic monitoring strategy was performed based on FRET between Au NCs and ICG, suggesting that Au NCs-INPs could be utilized to evaluate the therapeutic response by real-time monitoring the change in Au NCs in fluorescence intensity together with ICG supersession. Therefore, Au NCs-INPs as a novel photosensitizer have great potentials for combined tumor imaging, therapy, and therapeutic monitoring in real time.


Assuntos
Verde de Indocianina/química , Transferência Ressonante de Energia de Fluorescência , Ouro , Osteonectina , Fármacos Fotossensibilizantes
17.
Acad Emerg Med ; 24(9): 1042-1050, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28646519

RESUMO

BACKGROUND: Policymakers argue that emergency department (ED) visits for conditions preventable with high-quality outpatient care contribute to waste in the healthcare system. However, access to ambulatory care is uneven, especially for vulnerable populations like minorities, the poor, and those with limited health literacy. The impact of limited health literacy on ED visits that are preventable with timely, high-quality ambulatory care is unknown. OBJECTIVE: The objective was to determine the association of health literacy with preventable ED visits. METHODS: We conducted an observational cross-sectional study of potentially preventable ED visits (outcome) among adults (≥18 years old) in an ED serving an urban community. We assessed health literacy (predictor) through structured interviews with the Rapid Estimate of Adult Literacy in Medicine (REALM). We recorded age, sex, race, employment, payer, marital and health status, and number of comorbidities through structured interviews or electronic record review. We identified potentially preventable ED visits in the 2 years before the index ED visit by applying Agency for Healthcare Research and Quality technical specifications to identify ambulatory care sensitive conditions using ED discharge diagnoses in hospital administrative data. We used Poisson regression to evaluate the number of preventable ED visits among patients with limited (REALM < 61) versus adequate (REALM ≥ 61) health literacy after adjusting for covariates. RESULTS: Of 1,201 participants, 709 (59%) were female, 370 (31%) were African American, mean age was 41.6 years, and 394 (33%) had limited health literacy. Of 4,444 total ED visits, 423 (9.5%) were potentially preventable. Of these, 260 (61%) resulted in hospital admission and 163 (39%) were treat and release. After covariates were adjusted for, patients with limited literacy had 2.3 (95% confidence interval [CI] = 1.7-3.1) times the number of potentially preventable ED visits resulting in hospital admission compared to individuals with adequate health literacy, 1.4 (95% CI = 1.0-2.0) times the number of treat-and-release visits, and 1.9 (95% CI = 1.5-2.4) times the number of total preventable ED visits. CONCLUSIONS: Our results suggest that the ED may be an important site to deploy universal literacy-sensitive precautions and to test literacy-sensitive interventions with the goal of reducing the burden of potentially preventable ED visits on patients and the healthcare system.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Alfabetização em Saúde/estatística & dados numéricos , Mau Uso de Serviços de Saúde/prevenção & controle , Adulto , Assistência Ambulatorial/economia , Estudos Transversais , Serviço Hospitalar de Emergência/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
18.
Circ Res ; 120(12): 1947-1957, 2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28490433

RESUMO

RATIONALE: Intracoronary infusion of bone marrow (BM) mononuclear cells after acute myocardial infarction (AMI) has led to limited improvement in left ventricular function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans. OBJECTIVE: To test the hypothesis that peripheral blood (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and cardiac function after AMI. METHODS AND RESULTS: BM and PB samples were collected from 87 participants 14 to 21 days after AMI and BM from healthy donors was used as a reference. Correlations between cytokine concentrations and cell phenotypes, cell functions, and post-AMI cardiac function were determined. PB interleukin-6 (IL-6) negatively correlated with endothelial colony-forming cell colony maximum in the BM of patients with AMI (estimate±SE, -0.13±0.05; P=0.007). BM from healthy individuals showed a dose-dependent decrease in endothelial colony-forming cell colony outgrowth in the presence of exogenous IL-1ß or IL-6 (P<0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study participants, the angiogenic cytokine platelet-derived growth factor BB glycoprotein correlated positively with BM-derived colony-forming unit-endothelial colony maximum (estimate±SE, 0.01±0.002; P<0.001), multipotent mesenchymal stromal cell colony maximum (estimate±SE, 0.01±0.002; P=0.002) in BM, and mesenchymal stromal cell colony maximum in PB (estimate±SE, 0.02±0.005; P<0.001). CONCLUSIONS: Two weeks after AMI, increased PB platelet-derived growth factor BB glycoprotein was associated with increased BM function, whereas increased IL-6 was associated with BM impairment. Validation studies confirmed inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors may improve the regenerative capacity of BM cells after AMI. CLINICAL TRIAL REGISTRATIONS: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684060.


Assuntos
Células da Medula Óssea/fisiologia , Citocinas/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Infarto do Miocárdio/sangue , Medula Óssea/fisiologia , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico
19.
Acta Biochim Pol ; 64(1): 35-39, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27723845

RESUMO

Numerous evidences suggested that the hepatitis B virus (HBV) was recognized as an important factor in the development of hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) recently was reported to be involved in the progress of HCC. HBV may regulate DKK1 expression in hematoma carcinogenesis. Here, we demonstrated that HBV could regulate DKK1 promoter activity which resulted in upregulation of its mRNA and protein expression in several HBV existing cell lines, and HBx played a prominent role in this process. Transcription factor binding site search result showed that there is a SP1 site in DKK1 promoter region. Luciferase assay showed that overexpression of SP1 could increase DKK1 promoter activity in a dose dependent manner. Accordingly, siRNA inhibition of SP1 expression reduced DKK1 promoter activity and decreased the expression of DKK1 protein.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/genética , Fator de Transcrição Sp1/fisiologia , Transativadores/fisiologia , Sítios de Ligação , Linhagem Celular Tumoral , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Regiões Promotoras Genéticas , RNA Interferente Pequeno/farmacologia , Fator de Transcrição Sp1/antagonistas & inibidores , Fator de Transcrição Sp1/metabolismo , Proteínas Virais Reguladoras e Acessórias
20.
Theranostics ; 6(7): 1043-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27217837

RESUMO

Photoacoustic (PA) imaging and photothermal therapy (PTT) as light-induced theranostic platforms have been attracted much attention in recent years. However, the development of highly efficient and integrated phototheranostic nanoagents for amplifying PA imaging and PTT treatments poses great challenges. Here, we report a novel phototheranostic nanoagent using indocyanine green-loaded polydopamine-reduced graphene oxide nanocomposites (ICG-PDA-rGO) with amplifying PA and PTT effects for cancer theranostics. The results demonstrate that the PDA layer coating on the surface of rGO could effectively absorb a large number of ICG molecules, quench ICG's fluorescence, and enhance the PDA-rGO's optical absorption at 780 nm. The obtained ICG-PDA-rGO exhibits stronger PTT effect and higher PA contrast than that of pure GO and PDA-rGO. After PA imaging-guided PTT treatments, the tumors in 4T1 breast subcutaneous and orthotopic mice models are suppressed completely and no treatment-induced toxicity being observed. It illustrates that the ICG-PDA-rGO nanocomposites constitute a new class of theranostic nanomedicine for amplifying PA imaging and PTT treatments.


Assuntos
Neoplasias da Mama/terapia , Corantes/administração & dosagem , Grafite/administração & dosagem , Hipertermia Induzida , Indóis/administração & dosagem , Nanocompostos/administração & dosagem , Técnicas Fotoacústicas , Fototerapia , Polímeros/administração & dosagem , Animais , Neoplasias da Mama/diagnóstico por imagem , Modelos Animais de Doenças , Verde de Indocianina/administração & dosagem , Camundongos Endogâmicos BALB C , Óxidos/administração & dosagem , Nanomedicina Teranóstica/métodos , Resultado do Tratamento
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