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1.
Mol Oncol ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239639

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors around the world. Numerous studies have revealed the function of long noncoding RNAs (lncRNAs) in cancers, including ESCC. In this study, lncRNA small nucleolar RNA host gene 12 (SNHG12), mainly distributed in ESCC cell cytoplasm, was overexpressed in ESCC specimens and CD133+ cells. In CD133- ESCC cells, SNHG12 overexpression promoted cell proliferation, migration, epithelial-mesenchymal transition (EMT), and stemness and SNHG12 silencing led to opposite results. Furthermore, SNHG12 sequestered miR-6835-3p and induced the proto-oncogene, polycomb ring finger (BMI1). SNHG12 also enhanced the stability of CTNNB1, the mRNA encoding ß-catenin, via recruiting insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in ESCC. Rescue assays indicated that CTNNB1 and BMI1 were targets for SNHG12 to regulate ESCC cell proliferation, migration, EMT, and stemness. Furthermore, SOX4 (sex-determining region Y-box 4) bound with the SNHG12 promoter to transcriptionally activate SNHG12 in ESCC. Finally, in vivo data showed SNHG12 knockdown retarded tumorigenesis and metastasis in ESCC. In summary, SNHG12 induces proliferation, migration, EMT, and stemness of ESCC cells via post-transcriptional regulation of BMI1 and CTNNB1, indicating that targeting SNHG12 might be a novel target for ESCC treatment.

2.
Sci Rep ; 10(1): 721, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959881

RESUMO

Surface plasmon resonance (SPR) effect of noble metal nanoparticles (NPs) for photocatalysis has a significant enhancement. In this system, a plasmonic ternary hybrid photocatalyst of Ag/AgBr/g-C3N4 was synthetized and used in water splitting to generation H2 under visible light irradiation. 18%Ag/AgBr/g-C3N4 showed the highest photoactivity, with the efficiency of hydrogen generation as high as 27-fold to that of pristine g-C3N4. Compared to simple mixture of Ag/AgBr and g-C3N4, hetero-composite Ag/AgBr/g-C3N4 showed a higher photoactivity, even though they contained same content of Ag/AgBr. We find that significant factors for enhancing properties were the synergistic effect between Ag/AgBr and g-C3N4, and the light absorption enhancing by SPR effect of Ag NPs. Ag/AgBr NPs firmly anchored on the surface of g-C3N4 and their high dispersion were also responsible for the improved activity and long-term recycling ability. The structure of Ag/AgBr/g-C3N4 hybrid materials and their enhancement to photocatalytic activity were discussed. Meanwhile, the possible reaction mechanism of this system was proposed.

3.
Chem Biol Interact ; 317: 108946, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31935362

RESUMO

Trigonelline is a plant alkaloid that has generated interest for its neuroprotective roles in brain pathology. However, the protective effect of trigonelline on cerebral ischemia/reperfusion (I/R) injury and the potential mechanism have not been fully evaluated. Our results showed that trigonelline pretreatment ameliorated oxygen-glucose deprivation/reperfusion (OGD/R)-induced hippocampal neurons injury. The OGD/R-caused reactive oxygen species (ROS) generation and decreased concentrations of superoxide dismutases (SOD) and glutathione peroxidase (GPx) were markedly attenuated by trigonelline. In addition, the increased levels of TNF-α, IL-6 and IL-1ß in OGD/R-induced hippocampal neurons were significantly decreased by trigonelline pretreatment. Trigonelline also suppressed caspase-3 activity and bax expression, and induced bcl-2 expression in OGD/R-induced hippocampal neurons. Furthermore, trigonelline induced the activation of PI3K/Akt pathway in hippocampal neurons exposed to OGD/R condition. Inhibition of PI3K/Akt signaling reversed the protective effects of trigonelline on OGD/R-induced hippocampal neurons injury. Taken together, these findings indicated that trigonelline protected hippocampal neurons from OGD/R-induced injury, which was mediated by the activation of PI3K/Akt signaling pathway.


Assuntos
Alcaloides/farmacologia , Glucose/administração & dosagem , Hipocampo/citologia , Neurônios/efeitos dos fármacos , Oxigênio/administração & dosagem , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Alcaloides/antagonistas & inibidores , Animais , Isquemia Encefálica , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Inflamação , Morfolinas/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Transdução de Sinais/efeitos dos fármacos
4.
Bioact Mater ; 4: 346-357, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31720491

RESUMO

Implant-associated infections are generally difficult to cure owing to the bacterial antibiotic resistance which is attributed to the widespread usage of antibiotics. Given the global threat and increasing influence of antibiotic resistance, there is an urgent demand to explore novel antibacterial strategies other than using antibiotics. Recently, using a certain surface topography to provide a more persistent antibacterial solution attracts more and more attention. However, the clinical application of biomimetic nano-pillar array is not satisfactory, mainly because its antibacterial ability against Gram-positive strain is not good enough. Thus, the pillar array should be equipped with other antibacterial agents to fulfill the bacteriostatic and bactericidal requirements of clinical application. Here, we designed a novel model substrate which was a combination of periodic micro/nano-pillar array and TiO2 for basically understanding the topographical bacteriostatic effects of periodic micro/nano-pillar array and the photocatalytic bactericidal activity of TiO2. Such innovation may potentially exert the synergistic effects by integrating the persistent topographical antibacterial activity and the non-invasive X-ray induced photocatalytic antibacterial property of TiO2 to combat against antibiotic-resistant implant-associated infections. First, to separately verify the topographical antibacterial activity of TiO2 periodic micro/nano-pillar array, we systematically investigated its effects on bacterial adhesion, growth, proliferation, and viability in the dark without involving the photocatalysis of TiO2. The pillar array with sub-micron motif size can significantly inhibit the adhesion, growth, and proliferation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Such antibacterial ability is mainly attributed to a spatial confinement size-effect and limited contact area availability generated by the special topography of pillar array. Moreover, the pillar array is not lethal to S. aureus and E. coli in 24 h. Then, the X-ray induced photocatalytic antibacterial property of TiO2 periodic micro/nano-pillar array in vitro and in vivo will be systematically studied in a future work. This study could shed light on the direction of surface topography design for future medical implants to combat against antibiotic-resistant implant-associated infections without using antibiotics.

5.
Mol Cancer ; 18(1): 160, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722716

RESUMO

BACKGROUND: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. METHODS: Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3ß) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3ß, and the detection rates of plasma circGSK3ß for ESCC were investigated. RESULTS: We demonstrated that upregulated expression of circGSK3ß was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3ß promoted ESCC cell migration and invasion via direct interaction with GSK3ß and inhibiting GSK3ß activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3ß expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively. CONCLUSIONS: CircGSK3ß exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3ß have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.


Assuntos
Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , RNA Circular , Transdução de Sinais , beta Catenina/metabolismo , Adulto , Idoso , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Feminino , Imunofluorescência , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/química , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Relação Estrutura-Atividade , beta Catenina/química
6.
Nano Lett ; 19(12): 8343-8356, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31659907

RESUMO

Anisotropic hydrogels with a hierarchical structure can mimic biological tissues, such as neurons or muscles that show directional functions, which are important factors for signal transduction and cell guidance. Here, we report a mussel-inspired approach to fabricate an anisotropic hydrogel based on a conductive ferrofluid. First, polydopamine (PDA) was used to mediate the formation of PDA-chelated carbon nanotube-Fe3O4 (PFeCNT) nanohybrids and also used as a dispersion medium to stabilize the nanohybrids to form a conductive ferrofluid. The ferrofluid can respond to an orientated magnetic field and be programed to form aligned structures, which were then frozen in a hydrogel network formed via in situ free-radical polymerization and gelation. The resulted hydrogel shows directional conductive and mechanical properties, mimicking an oriented biological tissue. Under external electrical stimulation, the orientated PFeCNT nanohybrids can be sensed by the myoblasts cultured on the hydrogel, resulting in the oriented growth of cells. In summary, the mussel-inspired anisotropic hydrogel with its aligned structural complexity and anisotropic properties together with the cell affinity and tissue adhesiveness is a potent multifunctional biomaterial for mimicking oriented tissues to guide cell proliferation and tissue regeneration.

7.
J Stroke Cerebrovasc Dis ; 28(12): 104399, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31611168

RESUMO

OBJECTIVE: To examine racial/ethnic disparities in 30-day all-cause readmission after stroke. METHODS: Thirty-day all-cause readmission was compared by race/ethnicity among Medicare fee-for-service beneficiaries discharged for ischemic stroke from hospitals in the Florida Stroke Registry from 2010 to 2013. We fit a Cox proportional hazards model that censored for death and adjusted for age, sex, length of stay, discharge home, and comorbidities to assess racial/ethnic differences in readmission. RESULTS: Among 16,952 stroke patients (54% women, 75% white, 8% black, and 15% Hispanic), 30-day all-cause readmission was 15% (17.2% for blacks, 16.7% for Hispanics, 14.4% for whites, and 14.7% for others; P = .003). There was a median of 11 days between discharge and first readmission. In adjusted analyses, there was no significant difference in readmission for blacks (hazard ratio 1.15, 95% confidence interval 0.99-1.33), Hispanics (1.00, .90-1.13), and those of other race/ethnicity (.91, .71-1.16) compared with whites. Nearly 1 in 4 readmissions were attributable to acute cerebrovascular events: 16.6% ischemic stroke or transient ischemic attack, 1.5% hemorrhagic stroke, and 5.2% cerebral artery interventions. Interventions were more common among whites and those of other race than blacks and Hispanics (P = .029). Readmission due to pneumonia or urinary tract infection was 8.2%. CONCLUSIONS: Readmissions attributable to acute cerebrovascular events were common and generally occurred within 2 weeks of hospital discharge. Racial/ethnic disparities were present in readmissions for arterial interventions. Our results underscore the importance of postdischarge transitional care and the need for better secondary prevention strategies after ischemic stroke, particularly among minority populations.


Assuntos
Afro-Americanos , Isquemia Encefálica/terapia , Grupo com Ancestrais do Continente Europeu , Disparidades em Assistência à Saúde/etnologia , Hispano-Americanos , Benefícios do Seguro , Medicare , Readmissão do Paciente , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnologia , Feminino , Florida/epidemiologia , Humanos , Masculino , Recidiva , Sistema de Registros , Medição de Risco , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etnologia , Fatores de Tempo , Cuidado Transicional , Estados Unidos/epidemiologia
8.
Adv Healthc Mater ; 8(22): e1901103, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31609095

RESUMO

Repairing osteochondral defects is a considerable challenge because it involves the breakdown of articular cartilage and underlying bone. Traditional hydrogels with a homogenized single-layer structure cannot fully restore the function of osteochondral cartilage tissue. In this study, a mussel-inspired hydrogel with a bilayer structure is developed to repair osteochondral defects. The hydrogel is synthesized by simultaneously polymerizing two layers using a one-pot method. The resulting upper and lower gelatin methacryloyl-polydopamine hydrogel layers are used as cartilage and subchondral bone repair layers, respectively. Polydopamine-induced hydroxyapatite in situ mineralization takes place in the lower layer to mimic the structure of subchondral bone. The bilayer hydrogel exhibits good mechanical properties for the synergistic effect of covalent and noncovalent bonds, as well as nanoreinforcement of mineralized hydroxyapatite. To improve the tissue-inducibility of hydrogels, transforming growth factor ß3 is immobilized in the upper layer to induce cartilage regeneration, while bone morphogenetic protein 2 is immobilized in the lower layer to induce bone regeneration. Bone and cartilage repair performance of the hydrogel is examined by implantation into a full-thickness cartilage defect of a rabbit knee joint. The bilayer-structure hydrogel promotes regeneration of osteochondral tissue, thus providing a new option for repair of osteochondral defects.

9.
Front Oncol ; 9: 857, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552181

RESUMO

Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important. Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape. The overexpression of c-FLIPL occurs frequently in melanoma and its expression is associated with the prognosis. We found that the level of c-FLIPL expression was associated with the PD-1 blockade response rate in melanoma patients. Thus, we performed this research to investigate how c-FLIPL regulates immunotherapy in melanoma. We demonstrate that down regulation of c-FLIPL enhances the PD-1 blockade efficacy in B16 melanoma tumor model. Down regulation of c-FLIPL could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system. Moreover, knockdown of c-FLIPL could decrease the expression of PD-L1 and recruit more effector T cells in the tumor microenvironment. Our results may provide a new combined therapeutic target for further improving the efficacy of PD-1 blockade in melanoma.

10.
Nat Commun ; 10(1): 3672, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413315

RESUMO

Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (CRISPR-Cas12a- and aTF-mediated small molecule detector). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.


Assuntos
Proteínas Associadas a CRISPR , Sistemas CRISPR-Cas , Endodesoxirribonucleases , Fatores de Transcrição , Regulação Alostérica , Bioensaio , Clostridiales , Humanos , Limite de Detecção , Motivos de Nucleotídeos , Parabenos , Biologia Sintética , Ácido Úrico/sangue
11.
Stroke ; 50(8): 2101-2107, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31303151

RESUMO

Background and Purpose- We aimed to evaluate the current practice patterns, safety and outcomes of patients who receive endovascular therapy (EVT) having mild neurological symptoms. Methods- From Jan 2010 to Jan 2018, 127,794 ischemic stroke patients were enrolled in the Florida-Puerto Rico Stroke Registry. Patients presenting within 24 hours of symptoms who received EVT were classified into mild (National Institutes of Health Stroke Scale [NIHSS] ≤5) or moderate/severe (NIHSS>5) categories. Differences in clinical characteristics and outcomes were evaluated using multivariable logistic regression. Results- Among 4110 EVT patients (median age, 73 [interquartile range=20] years; 50% women), 446 (11%) had NIHSS ≤5. Compared with NIHSS >5, those with NIHSS ≤5 arrived later to the hospital (median, 138 versus 101 minutes), were less likely to receive intravenous alteplase (30% versus 43%), had a longer door-to-puncture time (median, 167 versus 115 minutes) and more likely treated in South Florida (64% versus 53%). In multivariable analysis younger age, private insurance (versus Medicare), history of hypertension, prior independent ambulation and hospital size were independent characteristics associated with NIHSS ≤5. Among EVT patients with NIHSS ≤5, 76% were discharged home/rehabilitation and 64% were able to ambulate independently at discharge as compared with 53% and 32% of patients with NIHSS >5. Symptomatic intracerebral hemorrhage occurred in 4% of mild stroke EVT patients and 6.4% in those with NIHSS >5. Conclusions- Despite lack of evidence-based recommendations, 11% of patients receiving EVT in clinical practice have mild neurological presentations. Individual, hospital and geographic disparities are observed among endovascularly treated patients based on the severity of clinical symptoms. Our data suggest safety and overall favorable outcomes for EVT patients with mild stroke.


Assuntos
Isquemia Encefálica/terapia , Procedimentos Endovasculares/métodos , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/terapia , Trombectomia , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Feminino , Florida , Humanos , Masculino , Pessoa de Meia-Idade , Porto Rico , Sistema de Registros , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Terapia Trombolítica , Resultado do Tratamento
12.
Colloids Surf B Biointerfaces ; 182: 110359, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352253

RESUMO

Multiple ions codoping may effectively modulate physicochemical and biological properties of hydroxyapatite (HA) for diverse biomedical applications. This study synthesized strontium (Sr)-, fluorine (F)- doped, and Sr/F-codoped HA nanoparticles by a hydrothermal method, and investigated the effect of ion doping on characteristics of HA, including crystallinity, crystal size, lattice parameters, and substitution sites by experiments and simulation with density functional theory (DFT) methods. It was found that, Sr doping increased the lattice parameters of HA whereas F doping decreased these parameters. Additionally, F doping enhanced the structural stability of the Sr-doped HA. F doping created excellent antibacterial properties to effectively inhibit growth of Streptococcus mutans. An appropriate Sr doping level endowed HA with optimum osteogenic ability to promote osteoblastic differentiation of bone marrow stem cells. These suggest that, Sr/F codoping is an effective approach to synthesizing HA-based materials with both antibacterial and osteogenic properties. More broadly, HA nanomaterials with specific characteristics may be designed for meeting diverse requirements from biomedical applications.


Assuntos
Antibacterianos/síntese química , Durapatita/química , Fluoretos/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/química , Osteoblastos/efeitos dos fármacos , Estrôncio/química , Antibacterianos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cristalização , Durapatita/farmacologia , Fluoretos/farmacologia , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Osteoblastos/citologia , Osteoblastos/fisiologia , Osteogênese/efeitos dos fármacos , Teoria Quântica , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/crescimento & desenvolvimento , Estrôncio/farmacologia , Engenharia Tecidual
13.
Nanoscale ; 11(34): 15846-15861, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31289795

RESUMO

Wound healing is a complex and dynamic process, and involves a series of events, which create a unique microenvironment at the wound sites. It is highly desirable to develop multi-functional skin substitutes which can play their roles in the whole healing processes to enhance the final healing efficiency. Herein, we fabricated a mussel-inspired chitosan/silk fibroin cryogel functionalized with near-infrared light-responsive polydopamine nanoparticles (PDA-NPs), as a multifunctional platform to regulate the wound microenvironment and enhance efficient wound healing. The cryogel has an extracellular matrix-like macroporous structure, mimicking the natural tissue environment, which allows cell attachment and tissue ingrowth. The cryogel shows high anti-oxidative activity to eliminate overproduced reactive oxygen species during inflammatory responses. Furthermore, the cryogel exhibits photothermally assisted antibacterial activity to prevent bacterial invasion. Thus, by combining the photobiostimulation of infrared light, the cryogel realizes bio-chemo-photothermal synergistic therapy for accelerating the complete skin-thickness wound healing by simultaneously suppressing adverse events due to its antibacterial activity and anti-oxidative ability, and promoting cell activities and tissue regeneration. Our work therefore presents the great promise shown by this multifunctional biopolymer cryogel as a flexible wound dressing with combinatory therapy for accelerating wound healing.


Assuntos
Bactérias/crescimento & desenvolvimento , Bandagens , Bivalves , Criogéis , Indóis , Nanopartículas/química , Polímeros , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/prevenção & controle , Animais , Criogéis/química , Criogéis/farmacologia , Indóis/metabolismo , Indóis/farmacologia , Masculino , Camundongos , Células NIH 3T3 , Polímeros/metabolismo , Polímeros/farmacologia , Ratos , Ratos Sprague-Dawley , Infecção dos Ferimentos/microbiologia
14.
Br J Psychiatry ; 215(2): 476-480, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31190652

RESUMO

BACKGROUND: Neighbourhood greenness or vegetative presence has been associated with indicators of health and well-being, but its relationship to depression in older adults has been less studied. Understanding the role of environmental factors in depression may inform and complement traditional depression interventions, including both prevention and treatment.AimsThis study examines the relationship between neighbourhood greenness and depression diagnoses among older adults in Miami-Dade County, Florida, USA. METHOD: Analyses examined 249 405 beneficiaries enrolled in Medicare, a USA federal health insurance programme for older adults. Participants were 65 years and older, living in the same Miami location across 2 years (2010-2011). Multilevel analyses assessed the relationship between neighbourhood greenness, assessed by average block-level normalised difference vegetative index via satellite imagery, and depression diagnosis using USA Medicare claims data. Covariates were individual age, gender, race/ethnicity, number of comorbid health conditions and neighbourhood median household income. RESULTS: Over 9% of beneficiaries had a depression diagnosis. Higher levels of greenness were associated with lower odds of depression, even after adjusting for demographics and health comorbidities. When compared with individuals residing in the lowest tertile of greenness, individuals from the middle tertile (medium greenness) had 8% lower odds of depression (odds ratio 0.92; 95% CI 0.88, 0.96; P = 0.0004) and those from the high tertile (high greenness) had 16% lower odds of depression (odds ratio 0.84; 95% CI 0.79, 0.88; P < 0.0001). CONCLUSIONS: Higher levels of greenness may reduce depression odds among older adults. Increasing greenery - even to moderate levels - may enhance individual-level approaches to promoting wellness.Declaration of interestNone.

15.
Small ; 15(25): e1805440, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31106983

RESUMO

Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS-scavenging, and osteoinductive porous Ti scaffold is prepared by the on-surface in situ assembly of a polypyrrole-polydopamine-hydroxyapatite (PPy-PDA-HA) film through a layer-by-layer pulse electrodeposition (LBL-PED) method. During LBL-PED, the PPy-PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy-PDA-HA films. Ultimately, the PPy-PDA-HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy-PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.

16.
Stroke ; 50(6): 1452-1459, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31084325

RESUMO

Background and Purpose- Ischemic stroke (IS) secondary to atrial fibrillation (AF) is largely preventable with the use of anticoagulation. We sought to identify race-ethnicity and sex disparities with the use of direct oral anticoagulants (DOACs), aspirin, and warfarin in IS patients with AF and to identify temporal trends in the utilization of these medications. Methods- The FLiPER-AF Stroke Study (Florida Puerto Rico Atrial Fibrillation) included 24 040 IS cases enrolled in the Florida-Puerto Rico Collaboration to Reduce Stroke Registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the effect of race-ethnicity and sex on utilization of DOACs, aspirin, and warfarin for stroke prevention in AF after adjustment for sociodemographic, hospital, and clinical factors. Results- Among 24 040 IS cases, 54% were women and 10% black, 12% FL-Hispanics, 4% PR-Hispanic, and 74% whites. From 2010 to 2016, DOAC use increased from 0% to 36%, warfarin use decreased from 51% to 17%, and aspirin use remained relatively stable (42%-40%). After adjustment, blacks had higher odds of warfarin (odds ratio, 1.22; 95% CI, 1.07-1.40) prescription at discharge compared with whites. Men had higher rates of aspirin (42.1% versus 38.8%), warfarin (33.6% versus 28.9%), and DOAC (21.3% versus 19.3%) use compared with women. After adjustment, women had lower odds of being discharged on aspirin (odds ratio, 0.92; 95% CI, 0.86-0.98) or warfarin (odds ratio, 0.91; 95% CI, 0.84-0.99). There was no sex difference in use of DOACs. Conclusions- Our study confirmed the increasing use of DOACs, downtrending use of warfarin, whereas aspirin use remained similar over the years. There are sex and race-ethnicity disparities in anticoagulation use in IS patients with AF. It is critical to understand underlying drivers of these disparities to develop better practice strategies for stroke prevention in patients with AF. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03627806.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Fibrilação Atrial , Isquemia Encefálica , Sistema de Registros , Acidente Vascular Cerebral , Varfarina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etnologia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etnologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Feminino , Florida/epidemiologia , Humanos , Masculino , Porto Rico/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
17.
Nat Commun ; 10(1): 1487, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940814

RESUMO

Adhesive hydrogels have gained popularity in biomedical applications, however, traditional adhesive hydrogels often exhibit short-term adhesiveness, poor mechanical properties and lack of antibacterial ability. Here, a plant-inspired adhesive hydrogel has been developed based on Ag-Lignin nanoparticles (NPs)triggered dynamic redox catechol chemistry. Ag-Lignin NPs construct the dynamic catechol redox system, which creates long-lasting reductive-oxidative environment inner hydrogel networks. This redox system, generating catechol groups continuously, endows the hydrogel with long-term and repeatable adhesiveness. Furthermore, Ag-Lignin NPs generate free radicals and trigger self-gelation of the hydrogel under ambient environment. This hydrogel presents high toughness for the existence of covalent and non-covalent interaction in the hydrogel networks. The hydrogel also possesses good cell affinity and high antibacterial activity due to the catechol groups and bactericidal ability of Ag-Lignin NPs. This study proposes a strategy to design tough and adhesive hydrogels based on dynamic plant catechol chemistry.


Assuntos
Adesivos/química , Catecóis/química , Hidrogéis/química , Lignina/química , Nanopartículas/química , Extratos Vegetais/química , Prata/química , Oxirredução , Polímeros/química
18.
Cell Death Dis ; 10(5): 339, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31000693

RESUMO

Recent studies have demonstrated that the androgen receptor (AR) could play important roles to promote renal cell carcinoma (RCC) cell proliferation, and other studies have also indicated that suppressing the argininosuccinate synthase 1 (ASS1) could promote proliferation of various tumors. The potential of AR promoting cell proliferation in RCC via altering ASS1, however, remains unclear. Here we found that the expression of ASS1 was lower in RCC tissues than in adjacent normal renal tissues, and a lower ASS1 expression was linked to a worse prognosis in RCC patients. Mechanism dissection showed that AR could decrease ASS1 expression to promote RCC cell proliferation via ASS1P3, a pseudogene of ASS1. The results of RIP assay and AGO2 assay revealed that AR could bind ASS1P3 to increase RCC cell proliferation via altering miR-34a-5p function, which could bind to the 3'UTR of ASS1 to suppress its protein expression. ASS1P3 could function as a miRNA decoy for miR-34a-5p to regulate ASS1 in RCC. Preclinical study also supports the in vitro data. Together, these results demonstrated that ASS1P3 could function as a competing endogenous RNA to suppress RCC cell progression, and targeting this newly identified AR-mediated ASS1P3/miR-34a-5p/ASS1 signaling might help in blocking proliferation.

19.
Colloids Surf B Biointerfaces ; 179: 470-478, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31005742

RESUMO

The scaffold for bone tissue engineering should possess proper porosity, adequate mechanical properties, cell affinity for cell attachment, and the capability to bind bioactive agents to induce cell differentiation. In this study, we successfully prepared a porous hydroxyapatite (HA) scaffold that is functionalized by poly(L-lysine)/polydopamine (PLL/PDA) hybrid coating. The PLL/PDA coating takes advantages of the high protein and cell affinity of PDA, as well as the biodegradability of PLL. Therefore, the coating can anchor bone morphogenic protein-2 (BMP2) to the HA scaffold via catechol chemistry under a mild condition so as to protect the bioactivity of BMP2. Meanwhile, the coating can also release BMP2 in a tunable and sustainable manner as the PLL degrades in the physiological environment. The BMP2-entrapped PLL/PDA coating on the HA scaffold can more efficiently promote osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro and induce ectopic bone formation to a much greater level in vivo compared with a bare HA scaffold that delivers BMP2 in a burst manner. All of these results suggest that the PDA-mediated catechol modification of the HA scaffold can be an effective strategy to develop sustainable protein delivery system, and that the PLL/PDA-coated HA scaffold could be a promising candidate for bone tissue engineering applications.


Assuntos
Bivalves/química , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/fisiologia , Materiais Revestidos Biocompatíveis/farmacologia , Durapatita/farmacologia , Tecidos Suporte/química , Animais , Proteína Morfogenética Óssea 2/farmacologia , Osso e Ossos/efeitos dos fármacos , Células Cultivadas , Liberação Controlada de Fármacos , Indóis/química , Polilisina/química , Polímeros/química , Porosidade , Ratos Sprague-Dawley
20.
J Phys Chem B ; 123(15): 3372-3382, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30913384

RESUMO

The interactions between osteogenic proteins and the biomaterial surface are crucial to the application of biomaterials, in which the conformational or orientational change of the adsorbed protein on the solid surfaces is one of the most important interactions other than the protein adsorption. Although some progress has been made in the mechanism of protein adsorption on the surface of hydroxyapatite (HAP) in recent years, there is still insufficient atomistic/molecular information about the conformation and orientation of proteins upon adsorbing on solid surfaces. In this study, different orientations and conformations of bone morphological protein-2 (BMP-2) adsorbed on the surface of HAP were calculated through the protein-solid surface docking approach; the relationship between optimal adsorption and biological activity of BMP-2 was investigated by applying a combination of molecular dynamic simulation (MD) and steered molecular dynamic simulation (SMD). Two optimal adsorption conformers were screened out according to the docking results on the basis of orientations of BMP-2 with different epitopes. Subsequent MD and SMD results showed that the knuckle epitope of BMP-2 was easier to adsorb on the surface of HAP(100) than the wrist epitope accompanying certain conformational changes. Such an absorption mode led to the wrist epitope of BMP-2 being exposed to the environment and then being identified/interacted with type I receptors on the stem cell membrane, which further induces the differentiation of stem cells into osteoblasts. Current simulation provided a theoretical high-throughput screening method for the protein-biomaterial adsorption states. It can be extended to more research on different protein adsorptions on the surface of different materials. The simulation results provided more information at the molecular and atomic levels to further interpret the mechanism of osteoinductivity from the perspective of growth factor adsorption. Meanwhile, we believe that it should be a meaningful attempt to screen biomaterial key factors by the high-throughput method, which might become a promising way to develop or optimize new biomaterials.

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