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A BODIPY-based fluorophore decorated with a gold specific reactive handle (e.g., 2-alkynylallyl alcohol) displayed a ratiometric fluorescence change in response to Au3+ ions with extraordinary selectivity over other competing metal species, including Hg2+, Cu2+, Zn2+ and Pd2+. By way of a gold-catalyzed intramolecular cyclisation-isomerisation reaction sequence, a BODIPY construct with an extended π-conjugation transformed into a new structure with a relatively short π-system. This unique chemical transformation was accompanied by, and resulted in, a dramatic shift in the emission and absorption wavelength, which could be monitored as distinct changes in the color of the solution's emission. Apart from its outstanding analytical performance in solution, including a quick response time (<10 s), unique specificity, a high-fold ratiometric change (62-fold), and a remarkably low detection limit (358 nM), the probe also proved useful in monitoring Au3+ ions in human cells and plants (e.g., Nicotiana benthamiana).
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A phenalenone based "turn on" probe was developed for selective and sensitive detection of Fe3+ ions in aqueous solutions. The thiophene-2-carboxaldehyde (receptor unit) was integrated into the 6-amino-1-phenalenone (6-AP) (signal reporter unit) through the C = N bond formation. The probe, 6-APT, operated through subsequent hydrolysis of the C = N bond induced by the coordination of Fe3+ ions to the heteroatoms to form highly fluorescent 6-AP. The probe displayed remarkable characteristics such as rapid response time (< 1 min), high analyte selectivity, and low limit of detection (1.3 µM). The sensing approach offered an accurate method for the detection of Fe3+ ions in real water samples (tap water and drinking water). In addition to the fluorometric response, the presence of Fe3+ ions can be monitored under daylight by the change in the color of the solution. Importantly, this study is the first example of a phenalenone-based sensor developed for metal ion sensing in literature.
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PURPOSE: The relentless rise in antimicrobial resistance is a major societal challenge and requires, as part of its solution, a better understanding of bacterial colonization and infection. To facilitate this, we developed a highly efficient no-wash red optical molecular imaging agent that enables the rapid, selective, and specific visualization of Gram-positive bacteria through a bespoke optical fiber-based delivery/imaging endoscopic device. METHODS: We rationally designed a no-wash, red, Gram-positive-specific molecular imaging agent (Merocy-Van) based on vancomycin and an environmental merocyanine dye. We demonstrated the specificity and utility of the imaging agent in escalating in vitro and ex vivo whole human lung models (n = 3), utilizing a bespoke fiber-based delivery and imaging device, coupled to a wide-field, two-color endomicroscopy system. RESULTS: The imaging agent (Merocy-Van) was specific to Gram-positive bacteria and enabled no-wash imaging of S. aureus within the alveolar space of whole ex vivo human lungs within 60 s of delivery into the field-of-view, using the novel imaging/delivery endomicroscopy device. CONCLUSION: This platform enables the rapid and specific detection of Gram-positive bacteria in the human lung.
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Fibras Ópticas , Staphylococcus aureus , Endoscopios , Bacterias Grampositivas , Humanos , Pulmón/diagnóstico por imagenRESUMEN
With the aid of bioorthogonal chemistry, we demonstrate the fabrication of synthetic dendrimers in situ around living cells. Using tetrazine dienophile and aminooxyl/hydrazide aldehyde chemistries, the density of functional groups on the dendrimers exponentially amplified intensities of fluorescent markers in antibody-targeted live cell imaging. This novel "swarming" approach highlights the power of bioorthogonal chemistry and provides a route to non-natural chemical structures on cells, paving the way for the generation of various artificial cellular nanostructures and scaffolds.
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OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have been determined as a new prognostic indicator of immunotherapy response in breast cancer (BC). The aim of this study is to investigate the effectiveness of imaging features in predicting the TIL levels in invasive BC patients. METHODS: A total of 158 patients with invasive BC were included in our study. All lesions were evaluated based on the BIRADS lexicon. US was performed for all the patients and 89 of them underwent MRI. The histologic stromal TIL (sTIL) levels were assessed and associations between the sTIL levels and imaging features were evaluated. RESULTS: Tumors with high sTIL levels had more circumscribed margins, round shape, heterogeneous echogenicity, and larger size on ultrasonography (p < 0.005). There was a statistically significant positive correlation between the sTIL levels and ADC value (p < 0.001). Tumors with high sTIL levels had significantly more homogeneous enhancement than the tumors with low sTIL levels (p = 0.001). Logistic regression analysis showed that the ADC was the most statistically significant parameter in predicting the sTIL levels (the odds ratio was 90.952; p = 0.002). The optimal cutoff value for ADC in predicting low and high sTIL levels was found to be 0.87 × 10-3 mm2 s-1 (AUC = 0.726, 73% specificity, and 60% sensitivity). CONCLUSIONS: Imaging findings, especially the ADC, may play an important role as an adjunct tool in cases of uncertain situations and may improve the accuracy of biopsy results. The prediction of sTIL levels using imaging findings may give an opportunity to predict prognosis. KEY POINTS: ⢠Preoperative assessment of TILs is an important biomarker of prognosis and treatment efficacy. ⢠ADC value can be a useful tool in distinguishing high and low sTIL levels as a non-invasive method. ⢠The prediction of sTIL levels using imaging findings may give an opportunity to predict prognosis and an optimal treatment for the BC patients.
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Neoplasias de la Mama/patología , Imagen de Difusión por Resonancia Magnética/métodos , Linfocitos Infiltrantes de Tumor/patología , Ultrasonografía Mamaria/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , PronósticoRESUMEN
Numerous optodes, with fluorophores as the chemical sensing element and optical fibres for light delivery and collection, have been fabricated for minimally invasive endoscopic measurements of key physiological parameters such as pH. These flexible miniaturised optodes have typically attempted to maximize signal-to-noise through the application of high concentrations of fluorophores. We show that high-density attachment of carboxyfluorescein onto silica microspheres, the sensing elements, results in fluorescence energy transfer, manifesting as reduced fluorescence intensity and lifetime in addition to spectral changes. We demonstrate that the change in fluorescence intensity of carboxyfluorescein with pH in this "high-density" regime is opposite to that normally observed, with complex variations in fluorescent lifetime across the emission spectra of coupled fluorophores. Improved understanding of such highly loaded sensor beads is important because it leads to large increases in photostability and will aid the development of compact fibre probes, suitable for clinical applications. The time-resolved spectral measurement techniques presented here can be further applied to similar studies of other optodes.
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Photodynamic inactivation of microorganisms has gained substantial attention due to its unique mode of action, in which pathogens are unable to generate resistance, and due to the fact that it can be applied in a minimally invasive manner. In photodynamic therapy (PDT), a non-toxic photosensitizer (PS) is activated by a specific wavelength of light and generates highly cytotoxic reactive oxygen species (ROS) such as superoxide (O2-, type-I mechanism) or singlet oxygen (1O2*, type-II mechanism). Although it offers many advantages over conventional treatment methods, ROS-mediated microbial killing is often faced with the issues of accessibility, poor selectivity and off-target damage. Thus, several strategies have been employed to develop target-specific antimicrobial PDT (aPDT). This includes conjugation of known PS building-blocks to either non-specific cationic moieties or target-specific antibiotics and antimicrobial peptides, or combining them with targeting nanomaterials. In this review, we summarise these general strategies and related challenges, and highlight recent developments in targeted aPDT.
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Antiinfecciosos/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/farmacología , Animales , Humanos , Concentración de Iones de Hidrógeno , Liposomas/química , Ratones , Micelas , Oligosacáridos/química , Péptidos/química , Polímeros/química , Oxígeno Singlete/química , Electricidad Estática , SuperóxidosRESUMEN
Recently, development of fluorescent nanoparticle-based probes for various bioimaging applications has attracted great attention. This work aims to develop a new type fluorescent nanoparticle conjugate and evaluate its cytotoxic effects on A549 and BEAS 2B cell lines. Throughout the study, ionically crosslinked chitosan nanoparticles (CNs) were conjugated with carboxylated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY-COOH). The results of conjugates (BODIPY-CNs) were investigated with regard to their physic-chemical, optical, cytotoxic properties and cellular internalization. The morphology of BODIPY-CNs was found to be spherical in shape and quite uniform having average diameter of 70.25 ± 11.99 nm. Cytotoxicty studies indicated that although BODIPY-COOH itself was quite toxic on both A549- and BEAS 2B-treated cells, CNs increased the cell viability of both cell lines via conjugation to BODIPY-COOH fluorescent molecule up to 67% for A549 and 74% for BEAS 2B cells. These results may suggest a possible utilization of the new fluorescent nanoparticle-based probe for bioimaging in biology and medicine.
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Bronquios/metabolismo , Quitosano/metabolismo , Colorantes Fluorescentes/metabolismo , Nanopartículas/metabolismo , Porfobilinógeno/análogos & derivados , Mucosa Respiratoria/metabolismo , Absorción Fisiológica , Bronquios/citología , Bronquios/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quitosano/efectos adversos , Quitosano/química , Diagnóstico por Imagen/efectos adversos , Dispersión Dinámica de Luz , Colorantes Fluorescentes/efectos adversos , Colorantes Fluorescentes/química , Humanos , Microscopía de Fuerza Atómica , Microscopía Confocal , Microscopía Electrónica de Rastreo , Nanopartículas/efectos adversos , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Porfobilinógeno/efectos adversos , Porfobilinógeno/química , Porfobilinógeno/metabolismo , Mucosa Respiratoria/citología , Mucosa Respiratoria/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
An ESIPT-based fluorescent dye, 3-hydroxyflavone, is chemically masked with an electrophilic cyanate motif in order to construct a fluorescent probe for cellular sulfur species. This novel probe structure, displays an extremely fast, highly sensitive and selective "turn-on" type fluorescent response toward H2S. We have also documented its utility for imaging of H2S in the living cells.
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Cianatos/química , Flavonoides/química , Colorantes Fluorescentes/química , Sulfuro de Hidrógeno/análisis , Sulfuro de Hidrógeno/química , Línea Celular Tumoral , Supervivencia Celular , Fluorescencia , Humanos , Estructura Molecular , Espectrometría de FluorescenciaRESUMEN
Drawing upon a consecutive amide coupling and intramolecular cyclisation pathway, a one-pot, straightforward synthetic route has been developed for a range of pyrazole fused γ-pyrone derivatives. The reaction mechanism proposed for the chemoselective formation of γ-pyranopyrazole is furthermore fully supported by experimental and computational studies.
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A fluorescent probe that displays a ratiometric fluorescence response towards gold and mercury ions has been devised. Emitting at a relatively longer wavelength, the conjugated form of the fluorescent dye transforms in the presence of the gold or mercury ions into a new dye, the molecular structure of which lacks the conjugation and consequently emits at a distinctly shorter wavelength.
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A significant compound in living organisms, hydrogen peroxide (H2O2) plays a dual role as a signalling molecule in cellular communication and as a pivotal biomarker in assessing disease and oxidative stress. Thus, the detection of abnormal changes in H2O2 levels is essential to understanding its function and involvement in biological systems. The growing demand to meet the specific needs for applications, particularly in biological systems, has sharpened focus on highly sensitive, highly selective molecular sensors and, in turn, heightened interest in these diagnostic tools with innovative designs. In our study, 2-aminophenalenone (2-AP) was used for the first time as a fluorophore in a fluorescent probe. The 2-APB molecule obtained from the reaction of 2-AP with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl chloroformate exhibited a highly selective and sensitive (i.e. 62 nM) detection profile for H2O2 compared with the other reactive oxygen species, anions, and metal cations. Moreover, offering naked-eye detection in aqueous solutions, 2-APB demonstrated excellent sensing performance, detection and real-time monitoring in relation to exogenous H2O2 in cells and endogenous H2O2 in zebrafish embryos.
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Colorantes Fluorescentes , Peróxido de Hidrógeno , Animales , Pez Cebra , Especies Reactivas de Oxígeno , Estrés OxidativoRESUMEN
Wearable bioelectronics represents a significant breakthrough in healthcare settings, particularly in (bio)sensing which offers an alternative way to track individual health for diagnostics and therapy. However, there has been no notable improvement in the field of cancer, particularly for skin cancer. Here, a wearable bioelectronic patch is established for transdermal sensing of the melanoma biomarker, tyrosinase (Tyr), using a microneedle array integrated with a surface-bound chemo-responsive smart probe to enable target-specific electrochemical detection of Tyr directly from human skin tissue. The results presented herein demonstrate the feasibility of a transdermal microneedle sensor for direct quantification of enzyme biomarkers in an ex vivo skin model. Initial performance analysis of the transdermal microneedle sensor proves that the designed methodology can be an alternative for fast and reliable diagnosis of melanoma and the evaluation of skin moles. The innovative approach presented here may revolutionize the landscape of skin monitoring by offering a nondisruptive means for continuous surveillance and timely intervention of skin anomalies, such as inflammatory skin diseases or allergies and can be extended to the screening of multiple responses of complementary biomarkers with simple modification in device design.
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Monofenol Monooxigenasa , Agujas , Dispositivos Electrónicos Vestibles , Humanos , Monofenol Monooxigenasa/metabolismo , Piel/metabolismo , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Biomarcadores/metabolismo , Biomarcadores/análisis , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Parche Transdérmico , Melanoma/metabolismo , Epidermis/metabolismo , Técnicas Electroquímicas/métodosRESUMEN
A rhodamine-based fluorescent probe, functionalized with an alkyne moiety, shows highly selective recognition towards Au(i) and Au(iii) ions over other metal ions. Probe is successfully employed for the determination of residual gold species in synthetic samples and monitoring the accumulation of gold ions in living cells.
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Técnicas de Química Analítica/instrumentación , Oro/análisis , Oro/química , Rodaminas/química , Catálisis , Supervivencia Celular , Colorantes Fluorescentes/química , Células HCT116 , HumanosRESUMEN
A new "turn on" fluorescent probe for the rapid and selective detection of Au3+ ions over other metal ions was developed. The probe design was constructed on a BODIPY-2-aminopyridine skeleton showing a weak fluorescence emission signal which increased substantially after the coordination of Au3+ ions. The probe displayed remarkable sensing performances such as a low limit of detection (17 nM), a short response time (<1 min), and ability in a wide range of pH's (6-11). The designed probe was found to have 2:1 coordination stoichiometry according to Job's plot analysis and most importantly to interact reversibly with Au3+ ions.
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Two methods involving the rhodium-catalyzed reaction of 2-en-4-yne acetates and the palladium-catalyzed reaction of 2-en-4-yne carbonates with organoboronic acids were investigated; both afforded exclusively the (E)-configured vinylallenes. The coordinative interaction of the rhodium with the acetate group promoted the δ-elimination of Rh(I)-OAc from the alkenylrhodium intermediate II in both syn and anti modes, with the syn-elimination being the major path. DFT calculations revealed that a conformer of this intermediate (II), which can lead to the (E)-configured vinylallene product via the syn-elimination mode, is energetically the most favorable conformer. The rhodium-catalyzed procedure is not applicable to reactions involving (E)-configured enyne acetates, because the geometry of the alkenylrhodium intermediate that is derived from the corresponding (E)-enyne acetate would not allow such coordinative interaction to occur. The palladium-catalyzed method, which proceeds through formation of the σ-vinylallenylpalladium intermediate, B, is suitable for both the (E)- and (Z)-configured enyne carbonates and appears to have a wider scope for both organoboronic acids and enyne substrates. The palladium-catalyzed reaction of an enantiomerically enriched enyne carbonate proceeded with racemization.
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We devised a new generation of halogen-based triplet sensitisers comprising geminal dibromides at the vinyl backbone of a BODIPY fluorophore. Incorporating geminal dibromides into the π-conjugation of BODIPY enhanced intersystem crossing due to the heavy atom effect, which in turn improved the extent of excited triplet states.
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Antineoplásicos/farmacología , Compuestos de Boro/farmacología , Bromuros/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Compuestos de Vinilo/farmacología , Células A549 , Antineoplásicos/química , Compuestos de Boro/química , Bromuros/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Imagen Óptica , Fármacos Fotosensibilizantes/química , Compuestos de Vinilo/químicaRESUMEN
The clinically used antifungal polyene amphotericin B was conjugated, via the mycosamine and the aglycon moieties, to fluorophores. The Cy5 conjugated probe showed selective labelling of fungi in the presence of bacteria, allowing multiplexed imaging and identification of microbial species in a co-culture of fungi and Gram-positive and Gram-negative bacteria.
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Anfotericina B/química , Colorantes Fluorescentes/química , Hongos/aislamiento & purificación , Antifúngicos , Bacterias , Técnicas de Cocultivo , Microscopía Confocal/métodos , Estructura MolecularRESUMEN
PURPOSE: The purpose of this study was to compare the multifocal (MF)/multicentric (MC) breast cancers with unifocal (UF) breast cancers in terms of tumour characteristics, treatment methods, loco-regional recurrence and survival rates. METHODS: Patients who were treated with a diagnosis of early-stage breast cancer (stage I,II) and had regular follow-up were included in the study. MF tumours were defined as having more than one tumour focus in the same quadrant, whereas MC tumours refered to the presence of more than one tumour focus in different quadrants. RESULTS: In total, 1865 patients with invasive breast cancer were evaluated, 1493 (80.1%) of whom had UF cancer, 330 (17.7%) had MF cancer, and 42 (2.3%) had MC cancer. After comparing the groups with each other, it was seen that MF and MC breast cancers occurred more often at early ages and that lymph node invasion (LNI) was greater. No differences were seen between the 3 groups in terms of local recurrence-free survival (RFS) and overall survival (OS) rates . In multivariate analysis, it was found that MF and MC tumours had no impact on local recurrence and OS. In multivariate analysis, it was understood that HER2 positivity and triple-negative breast cancer (TNBC) had an impact on local recurrence, and age, lymphovascular invasion (LVI), T3 tumour, lymph node positivity and TNBC subtype had an impact on OS. CONCLUSION: Although MC and MF tumours show aggressive features such as high lymph node positivity and LVI, they have similar loco-regional recurrence and survival rates to UF tumours.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Tasa de SupervivenciaRESUMEN
Irritable bowel syndrome (IBS) is a common disorder worldwide, but the diagnosis is often overlooked. This study aimed to evaluate the sociodemographic characteristics of IBS patients and the relationship between IBS and fibromyalgia. 202 patients with gastrointestinal system complaints who were admitted to Sisli Hamidiye Etfal Trainnig and Research Hospital, Family Medicine Clinic were included in the study. P < 0.05 was considered statistically significant. Fibromyalgia was associated with IBS in 26.7% of the participants. There was a positive correlation between the incidence of fibromyalgia and use of medication due to IBS, change in stool frequency, generalized pain, frequent illness, headache, excessive stress cancer anxiety , workforce loss due to IBS symptoms and fibromyalgia (p < 0.05). The presence of generalized pain, among IBS symptoms, caused the most robust increase in the likelihood of fibromyalgia (80%). The symptoms which were increasing the possibility of fibromyalgia were mostly generalized pain, high WHOQOL total score, family history of cancer, and loss of workforce at admission. IBS is a condition that affects the daily life quality of individuals and is often a condition that can be confused or associated with other diseases. Primary care physicians should approach patients holistically, especially in patients with generalized pain, family history of cancer, loss of workforce at admission, and more careful about fibromyalgia in patients with high WHOQOL total score. This awareness will increase the chances of early diagnosis and treatment of patients and will provide less cost but more effective treatment.