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1.
Anal Chem ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32192346

RESUMO

Accurate and sensitive imaging of hypoxia associated with inflammatory bowel disease (IBD) is significant for the precise diagnosis and treatment of this disease, but it remains a challenge for traditional hypoxia-activatable fluorescence probes because of a more moderate hypoxic state during IBD than under other pathological conditions. To address this issue, herein, we designed a hypoxia-activatable and cytoplasmic protein-powered fluorescence cascade amplifier, named HCFA, to image hypoxia associated with IBD in vivo. In our design, a 4-aminobenzoic acid (azo)-modified mesoporous silica nanoparticle (MSN) was used as a container to load black hole quencher 2 (BHQ2) and cytoplasmic protein-binding squarylium dye (SQ); then, the ß-cyclodextrin polymer (ß-CDP) combined with azo through a host-guest interaction to form HCFA. Upon passive stagnation in the inflamed tissue of IBD, the azo band would be cleaved under a hypoxic microenvironment, and SQ was released to activate the fluorescence of HCFA. Moreover, the unconstrained SQ can bind with cytoplasmic protein to exhibit drastic fluorescence intensity enhancement, realizing the fluorescence signal amplification for imaging of hypoxia. When one takes advantage of the large load capacity of MSN and the unique property of SQ, HCFA can sense oxygen levels in the range of 0% to 10%. Meanwhile, the fluorescence imaging results demonstrate that HCFA can sensitively distinguish different levels of cellular hypoxia and monitor the variations of hypoxia in vivo, highlighting HCFA as a promising tool for the detection of hypoxia associated with IBD.

2.
Anal Chem ; 92(5): 3555-3562, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008316

RESUMO

Tiagabine hydrochloride (TGB) is a clinically frequently used drug for anticonvulsion and reducing epileptic frequency. Over administration of TGB could bring about adverse effects, such as speech disorder, depression, and even suicidal tendencies. Therefore, accessible and sensitive assay for analysis of TGB becomes an urgent need toward guiding clinical medication. Here, we present the first report on fluorescence turn-on detection of TGB in urine testing. In this protocol, a fluorescent dye, perylene tetracarboxylic acid imide derivative (PTAI), is found specifically occupying the Sudlow site II of human serum albumin (HSA) and displays a new phenomenon of binding-induced quenching (BIQ). In presence of TGB, competitive binding of the TGB to the site II of HSA will trigger release of PTAI, thus successfully lighting up the fluorescence of PTAI. This label-free assay enjoys a broader working range (1-350 µM) and lower detection limit (0.218 µM) than the traditional liquid chromatography method and is uninterfered by the miscellaneous in the artificial urine. The BIQ probe highlights the merits of HSA as a quencher and a molecular recognition unit, and it opens up a way for studying drug-HSA interaction mechanism and noninvasive pharmaceutical testing.

3.
Oncol Rep ; 43(2): 471-480, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894345

RESUMO

The present study aimed to investigate the effect of miR­449a­mediated Notch signaling pathway on the proliferation, apoptosis and invasion of papillary thyroid carcinoma cells. Human papillary thyroid carcinoma cell line TPC­1 was selected, and cells were grouped and transfected: Control group (without any treatment), negative control (NC) group (transfection with NC plasmid), miR­449a mimic group (transfection with miR­449a mimic), miR­449a inhibitor group (transfection with miR­449a inhibitor), DAPT group (addition of γ­secretase inhibitor DAPT to inhibit the Notch signaling pathway), and miR­449a inhibitor + DAPT group (transfection with miR­449a inhibitor and addition of DAPT). The target relationship between miR­449a and Notch1 was detected by dual­luciferase reporter assay. qRT­PCR and western blotting were used to assess the expression of miR­449a, Notch1 and Jagged1 in cells. Cell proliferation was detected using EdU; the cell cycle and apoptosis were detected by flow cytometry; cell invasion ability was detected by Transwell assay. PCNA, MMP­2, MMP­9, Bcl­2 and Bax mRNA and protein expression were assessed by qRT­PCR and western blotting. The results revealed that miR­449a negatively regulated Notch1. Compared with the control group, there was significantly increased miR­449a expression in the miR­449a mimic group, and there was significantly decreased expression of Notch1, Jagged1, PCNA, MMP­2, MMP­9 and Bcl­2, increased Bax, reduced cell proliferation, increased G1­phase cell fraction, decreased S­phase cell fraction, an increased apoptosis rate, and decreased invasion ability in the miR­449a mimic group and DAPT group (all P<0.05). However, the results in the miR­449a inhibitor group were the opposite of those in miR­449a mimic group (all P<0.05). There was no significant difference in cell proliferation, apoptosis and invasion in the NC group and miR­449a inhibitor + DAPT group compared to the control group (all P>0.05). miR­449a overexpression can inhibit Notch signaling pathway, thereby inhibiting the proliferation and invasion of papillary thyroid carcinoma cells and promoting cell apoptosis.

4.
Chem Commun (Camb) ; 56(12): 1843-1846, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31950937

RESUMO

As the most abundant protein in blood, human serum albumin (HSA) is usually regarded as an interferent in clinical molecular diagnosis. Herein, we report that HSA is an endogenous signal amplifier for the detection of the prostate-specific antigen (PSA) in human plasma. This is the first study to utilize intrinsic biological components as the signal amplifier in blood tests.


Assuntos
Antígeno Prostático Específico/sangue , Albumina Sérica Humana/química , Butiratos/química , Corantes Fluorescentes/química , Humanos , Modelos Moleculares , Espectrometria de Fluorescência
5.
Chem Commun (Camb) ; 56(9): 1349-1352, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31904042

RESUMO

Herein, a novel two-photon ratiometric fluorescence assay was proposed for monitoring endogenous steroid sulfatase (STS) activity, which could be applied for the ratiometric imaging of STS activity in the endoplasmic reticulum of living cells and tissues and also could be used to distinguish estrogen-dependent tumor cells from other types of cells.


Assuntos
Corantes Fluorescentes/química , Naftalimidas/química , Esteril-Sulfatase/análise , Animais , Linhagem Celular Tumoral , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/toxicidade , Células HEK293 , Humanos , Limite de Detecção , Microscopia de Fluorescência/métodos , Simulação de Acoplamento Molecular , Naftalimidas/metabolismo , Naftalimidas/toxicidade , Fótons , Ligação Proteica , Esteril-Sulfatase/metabolismo
6.
Sensors (Basel) ; 20(2)2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31963953

RESUMO

The precision of target-based registration is related to the geometry distribution of targets, while the current method of setting the targets mainly depends on experience, and the impact is only evaluated qualitatively by the findings from empirical experiments and through simulations. In this paper, we propose a new quantitative evaluation model, which is comprised of the rotation dilution of precision (, assessing the impact of targets' geometry distribution on the rotation parameters) and the translation dilution of precision (, assessing the impact of targets' geometry distribution on the translation parameters). Here, the definitions and derivation of relevant formulas of the and are given, the experience conclusions are theoretically proven by the model of and , and an accurate method for determining the optimal placement location of targets and the scanner is proposed by calculating the minimum value of and . Furthermore, we can refer to the model ( and ) as a unified model of the geometric distribution evaluation model, which includes the model in GPS.

7.
Anal Chem ; 92(3): 2649-2655, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31920078

RESUMO

On the basis of a target microRNA (miRNA)-responsive DNA hydrogel, a novel surface-enhanced Raman scattering (SERS) sensor array with nine sensor units that can detect multiple cancer-related miRNAs in one sample was developed. The target miRNA-responsive DNA hydrogel was first formed in each sensor unit to realize the construction of the DNA hydrogel-based SERS sensor array. Initially, because of the blocking of the streptavidin (SA)-modified sensor units by the formed DNA hydrogel, the SERS tags (biotin/4-mercaptobenzonitrile-functionalized AuAg alloy nanoparticles (B/M-AuAgNPs)) could not pass through the hydrogel and bind to the SA-modified sensor surface; thus, obvious Raman signals could not be observed. After the introduction of the target miRNA, DNA hydrogels of the corresponding sensor unit were disintegrated accordingly, and SERS tags were able to pass through the hydrogel to be captured onto the SA-modified detection surface, thus resulting in strong Raman signals and the detection of target miRNA. The assay is validated under clean buffer conditions as well as in serum. This target miRNA-responsive DNA hydrogel-based SERS sensor array has attractive application prospects in cancer typing via blood miRNA measurements.

8.
Anal Chem ; 92(1): 583-587, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31818103

RESUMO

Herein, we describe a novel two-photon excitation/red emission-based ratiometric pH nanosensor consisting of a pH-sensitive two-photon dye and Tm3+-doped upconversion nanoparticles (UCNP). The fluorescence emission ratio between the dye (610 nm) and UCNPs (810 nm) (I610/I810) provides a linear indicator of pH values in the range from pH 4.0 to 6.5 with high sensitivity. These nanoprobes selectively accumulate in the lysosomes of cells, making them suitable for lysosomal pH tracking. This pH nanoprobe has been successfully applied in visualizing chemically stimulated changes of intracellular pH in living cells and tissues.

9.
Headache ; 59(10): 1743-1752, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31675102

RESUMO

OBJECTIVE: To assess the onset of efficacy for fremanezumab in chronic migraine by evaluating pain-related clinical measures at different time points. BACKGROUND: Faster onset of efficacy of preventive treatments could benefit patients with migraine. Fremanezumab is a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, a neuropeptide involved in the pathophysiology of migraine. In 12-week clinical trials, subcutaneous fremanezumab significantly reduced the frequency of migraine headaches, headache hours, and headaches in general, without serious treatment-related adverse events. New drug classes of migraine preventive treatment demonstrate markedly different clinical profiles from standard-of-care treatments. METHODS: In this double-blind phase III study, eligible patients were randomized 1:1:1 to receive subcutaneous injections of fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline, 225 mg at weeks 4 and 8), or placebo at each time point. This study included secondary, exploratory, and post hoc analyses of the primary trial, evaluating the change in headache days of at least moderate severity or migraine days during the first 4 weeks of the trial. RESULTS: A total of 1130 patients were randomized (fremanezumab quarterly, n = 376; fremanezumab monthly, n = 379; or placebo, n = 375). During the 4-week period after the first dose, the mean number of monthly headache days of at least moderate severity was reduced for the all-fremanezumab group (mean reduction [95% confidence interval]: -4.6 days [-5.1, -4.1]) compared with the placebo group (-2.3 days [-2.9, -1.6]; P < .0001). Treatment effects were observed at Week 1 for the all-fremanezumab group (-1.1 days [-1.3, -1.0]) vs placebo (-0.5 days [-0.7, -0.3]; P < .0001), with separation from placebo by Day 2 (P = .003). Similar effects were observed for the monthly average number of migraine days and mean number of monthly headache hours. CONCLUSIONS: The early onset of efficacy of fremanezumab may have the potential to improve patient compliance and clinical outcomes.

10.
Anal Chem ; 91(24): 15599-15607, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31762260

RESUMO

A new triplex-functionalized DNA tetrahedral nanoprobe is proposed herein for monitoring pH and messenger RNA (mRNA) in living cells. Different from traditional DNA tetrahedron-based nanoprobes, DNA triplex was employed to serve as important conformational conversion elements. Inspired by the low extracellular pH in tumor cells, the mRNA-targeted H1 and H2 were stably assembled on the extended short hairpin probes of DNA tetrahedron via Hoogsteen bonding to form DNA triplex. Due to the high intracellular pH and presence of target mRNA, hybridization chain reaction (HCR) was triggered between H1 and H2 which were released from the dissociation of DNA triplex, and the generated long double-stranded DNA activated a Föster resonance energy transfer (FRET) signal indicating target mRNA expression even at very low contents. By combining the distinguishing feature of DNA triplex structure (pH-responsive) and HCR (signal amplification), sensitive imaging of intracellular pH and tumor-related mRNA can be realized. As a further application, dynamic imaging of intracellular pH and mRNA during "mitochondria-dependent" pathway apoptosis was successfully achieved in human breast cancer cells, which indicated huge potential of our proposed nanoprobe in early diagnosis and treatment of diseases.

11.
Anal Chem ; 91(23): 15179-15186, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31713419

RESUMO

Fluorescence amplification is critical for in situ and real-time detection of intracellular low abundance biological species. However, current intracellular amplification techniques mainly rely on synthetic nucleic acid-based nanodevices, manipulating them in living cells remains challenging. To solve this problem, herein, a new signal amplification concept named cytoplasmic protein-powered in situ fluorescence amplification (CPFA) is proposed. CPFA takes cytoplasmic protein as cell-self-power for signal amplification enabling it to operate in living cells. To establish a prototype of CPFA, an amplifiable sensor for hydroxyl radicals (•OH) was designed by entrapping the screened cytoplasmic protein-enhanced fluorophore (PBF1) inside mesoporous silica (MSN) nanocontainer with ssDNA/PTAD-based signal switch. When encountered with •OH in living cells, the ssDNA was cleaved to separate PTAD from MSN, liberating multiple copies of the loaded PBF1 to light up the fluorescence. Furthermore, these released PBF1 molecules can instantly bind with cytoplasmic proteins to amplify their fluorescence signals. Take advantage of this two-stage amplification mode, the sensor in response to •OH exhibited remarkable fluorescence enhancement (near 400-fold) in cell lysates, and the •OH was linearly determined from 0 to 800 nM with a detection limit of 6.4 pM. Moreover, this sensor can track basal level and fluctuation of •OH in living cells on account of its high sensitivity. To our knowledge, this is the first effort to use cytoplasmic protein for amplifying detection signals, which will provide a new dimension to current methodologies for low-abundance biomarkers discovery and regulation for chemical biology and medical diagnostics.

12.
Cephalalgia ; : 333102419885905, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752521

RESUMO

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody targeting calcitonin gene-related peptide, has demonstrated efficacy for the preventive treatment of migraine in adults. OBJECTIVE: To evaluate the effect of fremanezumab treatment on acute headache medication use and migraine-associated symptoms in patients with episodic migraine. METHODS: In the Phase 3 HALO trial, patients with episodic migraine were randomized to receive subcutaneous fremanezumab monthly (225 mg at baseline, weeks 4 and 8), fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), or placebo over a 12-week period. The secondary endpoint was change from baseline in the monthly number of days with use of any acute headache mediation or migraine-specific acute headache medication; exploratory endpoints were change from baseline in the monthly number of days with nausea or vomiting, photophobia, or phonophobia. RESULTS: Of 875 patients randomized, 865 were included in the analysis (monthly, n = 287; quarterly, n = 288; placebo, n = 290). Baseline mean ± standard deviation days with: Any acute headache medication use (monthly: 7.7 ± 3.4; quarterly: 7.8 ± 3.7; placebo: 7.7 ± 3.6), migraine-specific acute headache medication use (6.1 ± 3.1; 6.6 ± 3.1; 7.1 ± 3.0), nausea or vomiting (4.5 ± 3.6; 4.9 ± 3.7; 4.5 ± 3.3) and photophobia and phonophobia (5.5 ± 4.1; 6.3 ± 4.1; 6.0 ± 3.9) were similar among treatment arms. Fremanezumab reduced the number of days of acute headache medication use ([least-squares mean change vs. placebo] monthly: -1.4 [95% confidence interval: -1.84, -0.89], p < 0.001; quarterly: -1.3 [-1.76, -0.82], p < 0.001) and migraine-specific acute headache medication use (monthly: -2.2 [-2.80, -1.56], p < 0.001; quarterly: -2.2 [-2.81, -1.58], p < 0.001) compared with placebo. Fremanezumab also reduced nausea or vomiting, photophobia, and phonophobia compared with placebo. CONCLUSIONS: Fremanezumab reduced the need for acute headache medications, including migraine-specific medications, while treating migraine-associated symptoms in patients with episodic migraine. TRIAL REGISTRATION: Clinicaltrials.gov NCT02629861.

13.
Anal Chem ; 91(24): 15974-15981, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31755263

RESUMO

Fluorescence molecular imaging has attracted increasing attention due to its various advantages. Lots of fluorophores have been developed to meet various molecular imaging needs. However, it is still inconvenient due to the lack of excellent fluorophores with an optically tunable group for biological molecular imaging. Here a new platform of a versatile long wavelength fluorophore with an optically tunable hydroxyl group was successfully developed by regulating molecular planarity and the twisted intramolecular charge transfer effect with a protected and deprotected hydroxyl group approach via "step by step" modifying strategy. As an excellent representative of this new type of fluorophore, LDOH-4 possesses good chemical and optical properties and shows a potential application prospect. As a proof-of-concept, a nitroreductase-activated TP fluorescent probe LDO-NTR was designed, which not only sensitively recognizes NTR with more than 310-fold response signal enhancement in vitro but also tracks NTR in a hypoxia tumor mouse model in vivo by using two-photon imaging. It is hopeful that the long wavelength fluorophore with the optically tunable hydroxyl group can serve as a useful platform to extend capable detection tools in biological chemistry and biomedical applications.

14.
Analyst ; 144(21): 6254-6261, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31560359

RESUMO

As VEGF mRNA is an endothelial cell-specific mitogen and a key regulator of angiogenesis in a variety of physiological and pathological processes, high expression levels of VEGF messenger RNA (mRNA) contribute to VEGF-driven angiogenesis in the hypoxic areas of solid tumors and then disrupt the vascular barrier, which may potentiate tumor cell extravasation. Thus, monitoring the changes in VEGF mRNA is necessary to understand the genetic programme under hypoxic conditions and thus facilitate risk assessment and risk reduction in hypoxic environments. Herein, a new fluorescent nanoprobe based on azoreductase-responsive functional metal-organic frameworks (AMOFs) was developed to realize the imaging of VEGF mRNA under hypoxic conditions. Since the azobenzene units in the AMOFs can be reduced to amines by the highly expressed azoreductase in an oxygen-deficient environment, the VEGF mRNA-targeted molecular beacon (MB), which is adsorbed on the surface of AMOFs via electrostatic interactions, can be released due to the structural damage of AMOFs. Moreover, TAMRA (carboxytetramethylrhodamine, donor) and Cy5 (acceptor) were close to each other due to the stem-loop conformation of MB, thus inducing high fluorescence energy resonance transfer (FRET) efficiency. Upon the addition of VEGF mRNA, the hybridization of VEGF mRNA destroyed the stem-loop conformation of MB, and then, the two fluorophores labeled on MB were separated with low FRET efficiency. This constructed fluorescent nanoprobe enables the quantitative analysis and in situ imaging of the VEGF mRNA level in living cells under hypoxic conditions. We expect that it will offer a potentially rich opportunity to understand the physiological processes of genetic programme.


Assuntos
Hipóxia Celular/fisiologia , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , NADH NADPH Oxirredutases/química , RNA Mensageiro/análise , Fator A de Crescimento do Endotélio Vascular/genética , Carbocianinas/química , Peptídeos Penetradores de Células/síntese química , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/toxicidade , DNA/química , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/toxicidade , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Hibridização de Ácido Nucleico , RNA Mensageiro/genética , Rodaminas/química
15.
Lancet ; 394(10203): 1030-1040, 2019 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-31427046

RESUMO

BACKGROUND: Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications. METHODS: The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed. FINDINGS: Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterly fremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI -3·8 to -2·4]; p<0·0001) and with monthly fremanezumab (LSM change -4·1 [0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverse events were similar for placebo and fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab. INTERPRETATION: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications. FUNDING: Teva Pharmaceuticals.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Transtornos de Enxaqueca/prevenção & controle , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Peptídeo Relacionado com Gene de Calcitonina/agonistas , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
16.
ACS Omega ; 4(5): 9074-9080, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459995

RESUMO

Fluorescent probes physisorbed on nanomaterials have emerged as a kind of useful and facile sensing platform for biological important molecules. However, nonspecific displacement in the physisorption systems is a non-negligible problem for the intracellular analysis. MIL (Materials of Institut Lavoisier), a subclass of metal-organic frameworks (MOFs), has high porosity, large surface area, and intriguing three-dimensional (3D) nanostructure with promising biological and biomedical applications such as molecular detection and drug delivery. Herein, we report MIL/aptamer-FAM as a nanosensor capable of resisting nonspecific displacement for intracellular adenosinetriphosphate (ATP) sensing and imaging. In this approach, by virtue of the remarkable quenching capability, high affinity of aptamers, and dramatic capability of resisting nonspecific displacement of 3D MIL-100, the assay and imaging of ATP in living cells were realized. Our results demonstrated that the MIL/aptamer-FAM nanosensor not only shows high selectivity for the detection of ATP in buffer but also is able to act as a "signal-on" nanosensor for specific imaging of ATP in living cells. The strategy reported here opens up a new way to develop MOF-based nanosensors for intracellular delivery and metabolite detection.

17.
ACS Appl Mater Interfaces ; 11(30): 26684-26689, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31276362

RESUMO

Here, we have developed a new colorimetric and luminescence nanosensor, based on upconversion nanoparticles (UCNPs), for in vitro and ex vivo measurement of carbon monoxide (CO). The nanoprobe has two strong fluorescence emission peaks in the UCNP core to excite fluorophores at 540 and 800 nm. The CO-responsive palladium ion-bounded rhodamine B derivatives (Pd-RBDs) are encapsulated in the mesoporous silica (mSiO2) shell and the particles outside the cyclodextrin (CD) layer. Reduction of palladium ions by CO results in the release of palladium from the Pd-RBDs, thereby inducing the closure of the spiro ring of the RBD and the accompanying reduction of rhodamine B (RB) absorption at 500-600 nm overlapping with the luminescence spectrum of UCNPs maximized at 540 nm. Therefore, the I540/I800 ratio of the nanoprobe will increase when CO is present, making it possible to quantitatively measure CO. Besides working in a clean buffer environment with known [CO], this method was evaluated using living cells and tissue sections. Additionally, these probes were also successfully used to investigate the CO-related protective activity of anti-hepatic ischemia-reperfusion injury (HIRI) oligopeptides.


Assuntos
Monóxido de Carbono/isolamento & purificação , Nanopartículas/química , Oligopeptídeos/farmacologia , Dióxido de Silício/química , Monóxido de Carbono/química , Humanos , Fígado/efeitos dos fármacos , Luminescência , Oligopeptídeos/química , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Rodaminas/química
18.
ACS Sens ; 4(8): 2124-2130, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31313911

RESUMO

Detection of biomarkers in complex samples is a significant health plan strategy for medical diagnosis, therapy monitoring, and health management. However, high background noise resulting from impurities and other analytes in complex samples has hampered the improvement of detection sensitivity and accuracy. Herein, an ultralow background biochip based on time-gated luminescent probes supported by photonic crystals (PCs) was successfully developed for detection of bladder cancer (BC)-related miRNA biomarkers with high sensitivity and specificity in urine samples. Coupled with the time-gated luminescence of long-lifetime luminescence probes and the luminescence-enhanced capability of PCs, the short-lived autofluorescence can be efficiently removed; thus, the detection sensitivity will be significantly improved. Benefiting from these merits, a detection limit of 26.3 fM is achieved. Furthermore, the biochip exhibits excellent performance in urinary miRNA detection, and good recoveries are also obtained. The developed biochip possesses unique properties of ultralow background and luminescence enhancement, thus offering a suitable tool for the detection of BC-related miRNA in urine. With rational design of probe sequences, the biochip holds great potential for many other biomarkers in real patient samples, making it valuable in areas such as medical diagnosis and disease evaluation.

19.
J Food Biochem ; 43(2): e12719, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31353663

RESUMO

Rosmarinic acid (RA), commonly found in Nepetoidae subfamily of Lamiaceae family, possesses various biological activities. To expand its application, RA was modified by esterification with methyl (me), propyl (pro), and hexyl (hex) alcohols and then tested antibacterial, α-glucosidase inhibitory, and lipid accumulation suppression activities. Consequently, RA derivatives enhanced antibacterial activity, especially the RA-pro and RA-hex, which effectively inhibited the growth of Bacillus cereus rather than tannic acid, a natural antibacterial agent. RA-hex also inhibited α-glucosidase inhibitory activity greater than luteolin. By computational molecular docking, dihydroxyphenyl group and hexyl group were selected as essential groups for interaction with the active site of α-glucosidase through hydrogen bonding and hydrophobic interaction, contributing to the great inhibitory activity. Furthermore, RA-pro and RA-hex effectively suppressed lipid accumulation of 3T3-L1 cells, superior to EGCG, a well-known anti-obesity phytochemical. These biological effects of RA derivatives commonly attributed to hydrophobicity, hydrogen bonding, and steric bulkiness of the side chain. PRACTICAL APPLICATIONS: Rosmarinic acid (RA), a fundamental compound in the family Lamiaceae, is one of powerful naturally occurring antioxidants as well as other biological activities. Furthermore, its abundance in nature was also high in amount in the plant kingdom. So, natural RA can be one of possible natural resources for creating potent natural drugs and biologically useful substances after chemical modification. Studies on various biological activities may intensively expand usage and application of RA. In this study, RA was derivatized to corresponding ester such as methyl, propyl, and hexyl alcohols with higher hydrophobicity, and found great antibacterial, α-glucosidase inhibitory, and lipid accumulation suppression activities. RA-pro and RA-hex significantly suppressed lipid accumulation and cell differentiation. Therefore, RA derivatives with multiple biological activities have the potential to be applied in the food and pharmaceutical industries as food ingredients and supplements.

20.
Stem Cell Res Ther ; 10(1): 229, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358069

RESUMO

The skin has important barrier, sensory, and immune functions, contributing to the health and integrity of the organism. Extensive skin injuries that threaten the entire organism require immediate and effective treatment. Wound healing is a natural response, but in severe conditions, such as burns and diabetes, this process is insufficient to achieve effective treatment. Epidermal stem cells (EPSCs) are a multipotent cell type and are committed to the formation and differentiation of the functional epidermis. As the contributions of EPSCs in wound healing and tissue regeneration have been increasingly attracting the attention of researchers, a rising number of therapies based on EPSCs are currently under development. In this paper, we review the characteristics of EPSCs and the mechanisms underlying their functions during wound healing. Applications of EPSCs are also discussed to determine the potential and feasibility of using EPSCs clinically in wound healing.

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