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1.
Nanoscale ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32342966

RESUMO

High performance photodetectors based on colloidal quantum dots have been demonstrated in a wide spectral range spanning from the visible to the mid infrared. Quantum dot photodetectors typically show a low-pass type spectral response with a tunable cutoff wavelength. In this paper, we propose a method for the realization of narrowband photodetectors based on the combination of photoconductors and optical filters, both realized with colloidal PbS quantum dots. We demonstrate that an array of such narrowband photodetectors can be effectively employed for the realization of a compact wavemeter operating in the visible and near-infrared spectral range.

2.
J Clin Med ; 9(4)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331426

RESUMO

BACKGROUND: The prognostic value of quick sepsis-related organ failure assessment (qSOFA) outside intensive care units has been criticized. Therefore, we aimed to improve its ability in predicting 30-day all-cause mortality, and in ruling out the cases at high risk of death among patients with suspected or confirmed sepsis at emergency department (ED) admission. METHODS: This study is a secondary analysis of a prospective multicenter study. We built three predictive models combining qSOFA with the clinical variables and serum biomarkers that resulted in an independent association with 30-day mortality, in both 848 undifferentiated patients (Group 1) and in 545 patients definitively diagnosed with sepsis (Group 2). The models reaching the highest negative predictive value (NPV) with the minimum expenditure of biomarkers in Group 1 and in Group 2 were validated in two cohorts of patients initially held out due to missing data. RESULTS: In terms of the area under the receiver-operating characteristic curve, all six models significantly exceeded qSOFA in predicting prognosis. An "extended" qSOFA (eqSOFA1) in Group 1 and an eqSOFA2 integrated with C-reactive protein and mid-regional proadrenomedullin (eqSOFA2+CRP+MR-proADM) in Group 2 reached the best NPV (0.94 and 0.93, respectively) and ease of use. eqSOFA1 and eqSOFA2+CRP+MR-proADM performed equally well in both the inception and validation cohorts. CONCLUSIONS: We have derived and validated two prognostic models that outweigh qSOFA in predicting mortality and in identifying the low risk of death among patients with suspected or confirmed sepsis at ED admission.

3.
J Phys Chem Lett ; 10(13): 3715-3726, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31244273

RESUMO

Ruling over the surface chemistry of metal halide perovskite nanocrystals (NCs) is crucial to access reliable luminophores. Here, we provide an atomic-level description of the surface of colloidal CsPbBr3 NCs, achieving an effective passivation strategy that leads to near-unity photoluminescence quantum yield. To this end, we used two different types of CsPbBr3 NCs, which had been synthesized with an outer shell of either oleylammonium bromide ion pairs or Cs-oleate complexes. We perturbed the dynamic equilibria at the NCs' surface with ligands from a comprehensive library, including amines (and their conjugated acids) with different basicities, chain lengths, and steric encumbrances. We demonstrate that control of both ligand binding affinity and ligand-to-NC molar ratio is essential to attain thermodynamically stable coordination of the NC surface. We thus present a reliable protocol for managing the surface chemistry of colloidal CsPbBr3 NCs and for selectively addressing their ligand-induced morphological (and structural) transformations.

4.
Nanoscale ; 11(19): 9478-9487, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31045198

RESUMO

Chemical species at the surface (ligands) of colloidal inorganic semiconductor nanocrystals (QDs) markedly impact the optoelectronic properties of the resulting systems. Here, post-synthesis surface chemistry modification of colloidal metal chalcogenide QDs is demonstrated to induce both broadband absorption enhancement and band gap reduction. A comprehensive library of chalcogenol(ate) ligands is exploited to infer the role of surface chemistry on the QD optical absorption: the ligand chalcogenol(ate) binding group mainly determines the narrowing of the optical band gap, which is attributed to the np occupied orbital contribution to the valence band edge, and mediates the absorption enhancement, which is related to the π-conjugation of the ligand pendant moiety, with further contribution from electron donor substituents. These findings point to a description of colloidal QDs that may conceive ligands as part of the overall QD electronic structure, beyond models derived from analogies with core/shell heterostructures, which consider ligands as mere perturbation to the core properties. The enhanced light absorption achieved via surface chemistry modification may be exploited for QD-based applications in which an efficient light-harvesting initiates charge carrier separation or redox processes.

5.
Crit Care Med ; 46(9): 1421-1429, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29742588

RESUMO

OBJECTIVES: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. DESIGN: Multicenter prospective study. SETTING: At emergency department admission in five University hospitals. PATIENTS: Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholipase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholipase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. CONCLUSIONS: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.


Assuntos
Algoritmos , Sepse/sangue , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Admissão do Paciente , Estudos Prospectivos
6.
J Phys Chem Lett ; 8(20): 5209-5215, 2017 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-28972763

RESUMO

Surface traps are ubiquitous to nanoscopic semiconductor materials. Understanding their atomistic origin and manipulating them chemically have capital importance to design defect-free colloidal quantum dots and make a leap forward in the development of efficient optoelectronic devices. Recent advances in computing power established computational chemistry as a powerful tool to describe accurately complex chemical species and nowadays it became conceivable to model colloidal quantum dots with realistic sizes and shapes. In this Perspective, we combine the knowledge gathered in recent experimental findings with the computation of quantum dot electronic structures. We analyze three different systems: namely, CdSe, PbS, and CsPbI3 as benchmark semiconductor nanocrystals showing how different types of trap states can form at their surface. In addition, we suggest experimental healing of such traps according to their chemical origin and nanocrystal composition.

7.
Nano Lett ; 17(2): 1248-1254, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28055216

RESUMO

Nowadays it is well-accepted to attribute bulk-like optical absorption properties to colloidal PbS quantum dots (QDs) at wavelengths above 400 nm. This assumption permits to describe PbS QD light absorption by using bulk optical constants and to determine QD concentration in colloidal solutions from simple spectrophotometric measurements. Here we demonstrate that PbS QDs experience the quantum confinement regime across the entire near UV-vis-NIR spectral range, therefore also between 350 and 400 nm already proposed to be sufficiently far above the band gap to suppress quantum confinement. This effect is particularly relevant for small PbS QDs (with diameter of ≤4 nm) leading to absorption coefficients that largely differ from bulk values (up to ∼40% less). As a result of the broadband quantum confinement and of the high surface-to-volume ratio peculiar of nanocrystals, suitable surface chemical modification of PbS QDs is exploited to achieve a marked, size-dependent enhancement of the absorption coefficients compared to bulk values (up to ∼250%). We provide empirical relations to determine the absorption coefficients at 400 nm of as-synthesized and ligand-exchanged PbS QDs, accounting for the broadband quantum confinement and suggesting a heuristic approach to qualitatively predict the ligand effects on the optical absorption properties of PbS QDs. Our findings go beyond formalisms derived from Maxwell Garnett effective medium theory to describe QD optical properties and permit to spectrophotometrically calculate the concentration of PbS QD solutions avoiding underestimation due to deviations from the bulk. In perspective, we envisage the use of extended π-conjugated ligands bearing electronically active substituents to enhance light-harvesting in QD solids and suggest the inadequacy of the representation of ligands at the QD surface as mere electric dipoles.


Assuntos
Chumbo/química , Pontos Quânticos/química , Sulfetos/química , Luminescência , Modelos Químicos , Nanotecnologia , Tamanho da Partícula , Propriedades de Superfície
8.
Angew Chem Int Ed Engl ; 55(23): 6628-33, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27038221

RESUMO

Colloidal quantum dots are composed of nanometer-sized crystallites of inorganic semiconductor materials bearing organic molecules at their surface. The organic/inorganic interface markedly affects forms and functions of the quantum dots, therefore its description and control are important for effective application. Herein we demonstrate that archetypal colloidal PbS quantum dots adapt their interface to the surroundings, thus existing in solution phase as equilibrium mixtures with their (metal-)organic ligand and inorganic core components. The interfacial equilibria are dictated by solvent polarity and concentration, show striking size dependence (leading to more stable ligand/core adducts for larger quantum dots), and selectively involve nanocrystal facets. This notion of ligand/core dynamic equilibrium may open novel synthetic paths and refined nanocrystal surface-chemistry strategies.

9.
J Am Chem Soc ; 137(5): 1875-86, 2015 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-25574692

RESUMO

Colloidal quantum dots (QDs) stand among the most attractive light-harvesting materials to be exploited for solution-processed optoelectronic applications. To this aim, quantitative replacement of the bulky electrically insulating ligands at the QD surface coming from the synthetic procedure is mandatory. Here we present a conceptually novel approach to design light-harvesting nanomaterials demonstrating that QD surface modification with suitable short conjugated organic molecules permits us to drastically enhance light absorption of QDs, while preserving good long-term colloidal stability. Indeed, rational design of the pendant and anchoring moieties, which constitute the replacing ligand framework leads to a broadband increase of the optical absorbance larger than 300% for colloidal PbS QDs also at high energies (>3.1 eV), which could not be predicted by using formalisms derived from effective medium theory. We attribute such a drastic absorbance increase to ground-state ligand/QD orbital mixing, as inferred by density functional theory calculations; in addition, our findings suggest that the optical band gap reduction commonly observed for PbS QD solids treated with thiol-terminating ligands can be prevalently ascribed to 3p orbitals localized on anchoring sulfur atoms, which mix with the highest occupied states of the QDs. More broadly, we provide evidence that organic ligands and inorganic cores are inherently electronically coupled materials thus yielding peculiar chemical species (the colloidal QDs themselves), which display arising (opto)electronic properties that cannot be merely described as the sum of those of the ligand and core components.


Assuntos
Absorção de Radiação , Chumbo/química , Fenômenos Ópticos , Pontos Quânticos/química , Sulfetos/química , Coloides , Ligantes , Luz , Modelos Moleculares , Conformação Molecular , Termodinâmica
10.
Intern Emerg Med ; 9(7): 749-57, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24362623

RESUMO

The objective of the study was to determine the accuracy of phospholipase A2 group II (PLA2-II), interferon-gamma-inducible protein 10 (IP-10), angiopoietin-2 (Ang-2), and procalcitonin (PCT) plasma levels in early ruling in/out of sepsis among systemic inflammatory response syndrome (SIRS) patients. Biomarker levels were determined in 80 SIRS patients during the first 4 h of admission to the medical ward. The final diagnosis of sepsis or non-infective SIRS was issued according to good clinical practice. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for sepsis diagnosis were assessed. The optimal biomarker combinations with clinical variables were investigated by logistic regression and decision tree (CART). PLA2-II, IP-10 and PCT, but not Ang-2, were significantly higher in septic (n = 60) than in non-infective SIRS (n = 20) patients (P ≤ 0.001, 0.027, and 0.002, respectively). PLA2-II PPV and NPV were 88 and 86%, respectively. The corresponding figures were 100 and 31% for IP-10, and 93 and 35% for PCT. Binary logistic regression model had 100% PPV and NPV, while manual and software-generated CART reached an overall accuracy of 95 and 98%, respectively, both with 100% NPV. PLA2-II and IP-10 associated with clinical variables in regression or decision tree heterogeneous models may be valuable biomarkers for sepsis diagnosis in SIRS patients admitted to medical ward (MW). Further studies are needed to introduce them into clinical practice.


Assuntos
Sepse/sangue , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Árvores de Decisões , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Modelos Logísticos , Masculino , Projetos Piloto
11.
Curr Drug Metab ; 14(5): 565-82, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23687927

RESUMO

Aptamer researches applied to the treatment of human cancers have increased since their discovery in 1990. This is due to different factors including: 1) the technical possibility to select, by SELEX-based procedures, specific aptamers targeting virtually any given molecule, 2) the aptamer favorable bio-activity in vivo, 3) the low production costs and 4) the ease synthesis and storage for the marketing. In the field of cancer treatments, aptamers have been studied as tumor-specific agents driving drugs into cancer cells; additionally they have been used as anti-neoplastic agents, able to inhibit tumor cell growth and dissemination when administered alone or in combination with conventional anti-neoplastic drugs. Aptamers are gaining an increased interest for pharmaceutical companies and some of them are under clinical evaluation trials. In this review we update the findings about the use of aptamers as "escort" molecules able to drive drugs into the cells and as antineoplastic drugs. Current anti-neoplastic treatments suffer from the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemotherapies into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemotherapies. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use.


Assuntos
Antineoplásicos/administração & dosagem , Aptâmeros de Nucleotídeos/química , Sistemas de Liberação de Medicamentos , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Ensaios Clínicos como Assunto , Desenho de Fármacos , Indústria Farmacêutica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia
12.
J Thromb Thrombolysis ; 34(4): 506-12, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22592842

RESUMO

Therapy with Vitamin K antagonists (VKA) effectively reduces the thrombosis risk in many clinical conditions. Genetic variants of vitamin K epoxide reductase (VKORC-1) are associated with increased VKA effect and bleeding risk. It is unknown whether these variants could also affect the long-term outcome in patients with high-dosage oral anticoagulation and/or more difficult adherence to the therapeutic INR range. Hundred and twenty-four patients with mechanical heart valve replacement assuming VKA were genotyped for VKORC-1 -1639G>A (Rs9923231) polymorphism. Hemorrhage, venous thrombosis and atherothrombotic events were retrospectively assessed for a 6-year period. Furthermore, stability of their INR in relationship with the VKORC-1 genotype was investigated day-by-day for 3 months. No differences were observed in hemorrhage and venous thrombosis events according to rs 9923231. GG genotype carriers (n = 41) had no atherothrombotic events, while 4 strokes, 4 TIA and 3 AMI were diagnosed in A carriers (n = 83; P = 0.0008). During the daily observation period, A allele carriers had lower VKA requirements (4.7, 3.7, 2.2 mg/day for GG/GA/AA genotype respectively; P = 0.00001), higher mean INR (2.7, 2.8, 2.9; P = 0.05) and a higher number of examinations above the therapeutic range than GG carriers (17 % vs. 0 % in GG genotype, P = 0.036). Conversely, patients with GG genotype had a more stable dosage of VKA (P = 0.006) and a higher percentage of examinations under the therapeutic range (51, 43 and 36 % in GG, GA and AA genotype, respectively, P = 0.040). In patients with high dosage VKA, VKORC-1 polymorphism is associated to a different warfarin dosage, anticoagulation level, time spent outside the therapeutic range and, in the long-term, a different incidence of atherothrombotic events.


Assuntos
Anticoagulantes/administração & dosagem , Próteses Valvulares Cardíacas , Oxigenases de Função Mista/genética , Polimorfismo Genético , Varfarina/administração & dosagem , Administração Oral , Idoso , Feminino , Seguimentos , Hemorragia/etiologia , Hemorragia/genética , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/genética , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genética , Fatores de Tempo , Trombose Venosa/etiologia , Trombose Venosa/genética , Vitamina K/antagonistas & inibidores , Vitamina K Epóxido Redutases
13.
Dig Liver Dis ; 43(12): 1006-14, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21831731

RESUMO

BACKGROUND: No effective therapy is available for hepatocellular carcinoma. To identify novel therapeutic strategies, we explored the effects of the depletion of E2F1, cyclin E1-E2 whose inter-relationships in hepatocellular carcinoma cell proliferation have never been defined. METHODS: siRNA-mediated depletion of the targets was studied in the hepatocellular carcinoma cells HepG2, HuH7 and JHH6 characterized by high, medium and low hepatocyte differentiation grade, respectively; a model of normal human hepatocytes was also considered. RESULTS: The depletion of each target mRNA reduced the levels of the other two mRNAs, thus demonstrating a close regulatory control, also confirmed by over-expression experiments. At the protein level, an exception to this trend was observed for cyclinE1 whose amount increased upon cyclin E2 (HepG2, HuH7, JHH6) and E2F1 (HepG2) depletion. In HepG2, reduced cyclinE1 proteolysis accounted for this observation. Additionally, cyclin E1-E2-E2F1 targeting decreased the levels of cyclin A2 mRNA and of the hyper-phosphorylated form of pRb thus leading to an S-phase cell decrease; migration was impaired as well. Finally, the model of human hepatocytes used was clearly less affected by target mRNAs depletion than hepatocellular carcinoma cells. CONCLUSION: Our data provide novel mutual relationships amongst cyclin E1-E2-E2F1 and indicate their role in sustaining hepatocellular carcinoma cell proliferation/migration, validating the concept of an anti-cyclin E1-E2-E2F1 therapeutic approach for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/metabolismo , Ciclina E/metabolismo , Ciclinas/metabolismo , Fator de Transcrição E2F1/metabolismo , Proteínas Oncogênicas/metabolismo , RNA Mensageiro/metabolismo , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Ciclina A2/genética , Ciclina A2/metabolismo , Ciclina E/genética , Ciclinas/genética , Regulação para Baixo , Fator de Transcrição E2F1/genética , Células Hep G2 , Humanos , Proteínas Oncogênicas/genética , Interferência de RNA , RNA Interferente Pequeno , Pontos de Checagem da Fase S do Ciclo Celular
14.
Chem Commun (Camb) ; 47(37): 10425-7, 2011 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-21853176

RESUMO

Selective nucleophilic substitution on a perfluorophenyl unit comprising a BODIPY fluorophore using an alkanethiol or a primary amine offers a quantitative fluorophore labelling strategy, while retaining high photostability and emission quantum yields approaching unity.


Assuntos
Aminas/química , Compostos de Boro/química , Corantes Fluorescentes/química , Hidrocarbonetos Fluorados/química , Compostos de Sulfidrila/química , Espectrometria de Fluorescência
15.
Atherosclerosis ; 215(1): 153-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21232745

RESUMO

OBJECTIVE: To assess the association of matrix metalloproteinases (MMP) genetic polymorphism (PM) with plaques vulnerability and clinical outcome of acute vascular events. METHODS: MMP-1 (-1607 G in/del), MMP-3 (-1171 A in/del), and MMP-9 microsatellite ((13-26) CA repeats around -90) PMs have been determined (i) in 204 patients with cerebrovascular disease to assess the association with features of vulnerability in carotid plaques and prevalence of stroke, (ii) in 208 patients with UA/NSTEMI to assess the association with in-hospital clinical outcome. RESULTS: Plaques from carriers of MMP-1 G insertion showed significantly smaller plaques and thicker fibrous cap. In CVD patients carrying such variant, Odds Ratio for previous stroke was 0.27 (95%C.I. 0.13-0.56, P=0.0002) and, in UA/NSTEMI patients, the risk of Major Adverse Cardiac Events (MACE, persistent angina, NSTEMI, and vascular death) was 0.22 (95%C.I. 0.11-0.44, P<0.0001). No variants in MMP-3 PM were associated to differences in either plaque features or clinical outcome. Carriers of MMP-9≥22 repeats in the microsatellite had larger plaques and lipid core. In CVD patients with such variant, Odds Ratio for stroke was 2.2 (95%C.I. 1.1-4.4) and, in UA/NSTEMI patients, MACE risk was 4.1 (95%C.I. 2.3-7.4, P<0.0001). Persistent angina and NSTEMI separately provided comparable results. CONCLUSIONS: Carriers of MMP-1 G insertion show smaller and more stable plaques, as well as better prognosis in acute vascular events, while patients with ≥22 repeats in MMP-9 have larger necrotic core and worse prognosis in UA/NSTEMI.


Assuntos
Angina Instável/genética , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Infarto do Miocárdio/genética , Placa Aterosclerótica/genética , Acidente Vascular Cerebral/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Polimorfismo Genético , Acidente Vascular Cerebral/patologia
16.
Curr Drug Metab ; 12(1): 11-23, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21222588

RESUMO

The RNA interference (RNAi) is a biological process by which a double stranded RNA (dsRNA also called small interfering RNA - siRNA) triggers the sequence-dependent degradation of a target RNA within the cellular environment. Thus siRNAs can be used to combat the expression of deleterious gene(s) causing disease or to destroy invading pathogen RNAs. Despite their enormous therapeutic potential, the use of siRNA as drugs presents two major problems: the difficulties to identify optimal delivery systems and the possible induction of different unwanted side effects. In this review, after presenting an overview about the mechanisms ruling the process of RNAi, we focus the attention on the description of the strategies developed to optimise systemic siRNA delivery; in this sense, considerations about the attempts to improve siRNA stability in the biological environment, the development of synthetic vectors for siRNA delivery, the siRNA bio-distribution and pharmacokinetics together with the selection of siRNA targeted delivery systems, are discussed. Since in the optimisation of the siRNA delivery systems the minimization of siRNA side effects should not be neglected, in the last part of the review we consider the problems related to the possible induction of siRNA mediated side effects focusing on the so called microRNA like off-targeting.


Assuntos
Inativação Gênica , Técnicas de Transferência de Genes , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/efeitos adversos , Animais , Transporte Biológico , Regulação da Expressão Gênica , Técnicas de Transferência de Genes/efeitos adversos , Vetores Genéticos , Humanos , MicroRNAs/efeitos adversos , Interferência de RNA , Estabilidade de RNA , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/uso terapêutico , Distribuição Tecidual
17.
J Am Chem Soc ; 133(2): 316-25, 2011 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-21182256

RESUMO

The self-assembly of a blue-emitting light-harvesting organogelator and specifically designed highly fluorescent tetracenes yields nanofibers with tunable emissive properties. In particular, under near-UV excitation, white light emission is achieved in organogels and dry films of nanofibers. Confocal fluorescence microspectroscopy demonstrates that each individual nanofiber emits white light. A kinetic study shows that an energy transfer (ET) occurs between the blue-emitting anthracene derivative and the green- and red-emitting tetracenes, while inter-tetracene ETs also take place. Moreover, microscopy unravels that the nanofibers emit polarized emission in the blue spectral region, while at wavelengths higher than 500 nm the emission is not significantly polarized.


Assuntos
Luz , Nanofibras/química , Naftacenos/síntese química , Transferência de Energia , Cinética , Microscopia Confocal , Estrutura Molecular , Naftacenos/química , Soluções
18.
J Am Coll Cardiol ; 56(11): 827-37, 2010 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-20813280

RESUMO

The prevalence of atrial fibrillation (AF) is related to age and is projected to rise exponentially as the population ages and the prevalence of cardiovascular risk factors increases. The risk of ischemic stroke is significantly increased in AF patients, and there is evidence of a graded increased risk of stroke associated with advancing age. Oral anticoagulation (OAC) is far more effective than antiplatelet agents at reducing stroke risk in patients with AF. Therefore, increasing numbers of elderly patients are candidates for, and could benefit from, the use of anticoagulants. However, elderly people with AF are less likely to receive OAC therapy. This is mainly due to concerns about a higher risk of OAC-associated hemorrhage in the elderly population. Until recently, older patients were under-represented in randomized controlled trials of OAC versus placebo or antiplatelet therapy, and therefore the evidence base for the value of OAC in the elderly population was not known. However, analyses of the available trial data indicate that the expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. An important caveat with warfarin treatment is maintenance of a therapeutic international normalized ratio, regardless of the age of the patient, where time in therapeutic range should be > or =65%. Therefore, age alone should not prevent prescription of OAC in elderly patients, given an appropriate stroke and bleeding risk stratification.


Assuntos
Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores Etários , Humanos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
20.
Biochimie ; 92(5): 455-63, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20144681

RESUMO

For hepatocellular carcinoma (HCC), a leading cause of cancer death world-wide, there is no effective therapy especially for the advanced stage of the disease. Thus, we started the investigations about a novel anti HCC approach based on the depletion of the transcription factor serum response factor (SRF) in HCC cell lines; SRF choice was based on its recently proposed contribution to HCC tissue development and on its important role in cell proliferation. SRF depletion, obtained by a siRNA (siSRF797), was studied in two HCC cell lines, i.e. HepG2 and JHH6 assigned to high and low hepatocytic differentiation grade on the base of the capacity to synthesize albumin. In the HCC cell lines examined, siSRF797 reduced both the mRNA and protein levels of SRF without inducing unspecific interferon response or cytotoxicity. Moreover, SRF depletion induced the reduction of S-phase cells and a decrease in cell number and vitality. Particularly in HepG2, cell growth impairment was paralleled by the decrease of the levels of the transcription factor E2F1 together with some of its regulated genes. In HepG2 but not in JHH6, SRF depletion was associated with apoptosis. Finally, in both HepG2 and JHH6, the combined administration of siSRF797 and bortezomib, a proteasome inhibitor whose therapeutic potential for HCC is considered attractive, further reduced cell viability compared to either siSRF797 or bortezomib treatment alone. In conclusion, SRF depletion affects the expansion of the high and low differentiation grade HCC cells HepG2 and JHH6. These results can pave the way to understand the role of SRF in HCC development and possibly to identify novel anti HCC therapeutic strategies.


Assuntos
Carcinoma Hepatocelular/patologia , Proliferação de Células , Inativação Gênica , Neoplasias Hepáticas/patologia , Fator de Resposta Sérica/metabolismo , Apoptose , Sequência de Bases , Western Blotting , Ciclo Celular , Linhagem Celular Tumoral , Primers do DNA , Técnicas de Silenciamento de Genes , Genes cdc , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Resposta Sérica/genética
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