Showing papers by "Bao-Xiang Zhao published in 2018"

A near-infrared ratiometric fluorescent probe for rapid and selective detection of hypochlorous acid in aqueous solution and living cells

Abstract: A new ratiometric fluorescent probe (XWJ) was developed on the basis of Forster resonance energy transfer (FRET). The probe constructed by dansyl and 2-(3,5,5-trimethylcyclohex-2-en-1-ylidene) malononitrile, exhibited a higher efficiency of energy transfer (up to 93.59%). The probe emerged excellent sensitivity and selectivity toward hypochlorous acid (HOCl). In particular, upon addition of HOCl, the probe can reveal a clear response in 25 s and manifest an obvious change in fluorescence colour from red to bright yellow, which could be recognized by naked eyes. Furthermore, the calibration curve is linear in the concentration range of 0–55 μM with the detection limit of 0.19 μM, which means that the probe can detect HOCl in low concentration. Besides, the fluorescence emission of the acceptor arises near-infrared region (NIR) and the probe possesses a large pseudo Stokes shift (300 nm) and well-separated dual emission (550/670 nm). The probe showed outstanding sensitivity and selectivity toward HOCl in cell imaging.

A new lipid droplets-targeted fluorescence probe for specific detection of SO2 derivatives in living cells

Abstract: A new lipid droplets-targeted fluorescence probe (HTF) for SO2 derivatives (HSO3−/SO32−) is developed based on FRET platform, in which a dansyl and 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene) malononitrile (TCF) derivative were combined by piperazine moiety. Besides a large Stokes shift (155 nm), probe HTF possesses high selectivity toward SO2 derivatives over other common anions or biothiols and excellent sensitivity with low detection limit (66 nM). The sensing mechanism was proposed to involve nucleophilic addition reaction of HSO3− to C C double bond, which was confirmed by 1H NMR titration and HR-MS spectra. Furthermore, HTF showed a low cytotoxicity and excellent lipid droplets-targeting in living cells. Its ratiometric fluorescence imaging hinted a good latent application for the monitor of exogenous and endogenous bisulfite in living cells.

A new water-soluble and mitochondria-targeted fluorescence probe for ratiometric detection of hypochlorous acid in living cells

Abstract: A new FRET-based ratiometric fluorescence probe for hypochlorous acid was developed. The FRET platform was constructed by a coumarin moiety as the energy donor and (E)-4-(4-(dialkylamino)styryl)-1-methylpyridin-1-ium iodide as the energy acceptor in which double bonds was recognition group for hypochlorous acid. Significantly, the water-soluble probe showed good selectivity, sensitivity, and lower detection limit (89 nM) for hypochlorous acid in optimal working condition. Moreover, the probe with good photo-stability and lower toxicity could successfully detect exogenous and endogenous hypochlorous acid and target mitochondria in living cells.

A pH probe inhibits senescence in mesenchymal stem cells.

Abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) are gradually getting attention because of its multi-directional differentiation potential, hematopoietic support, and promotion of stem cell implantation. However, cultured BMSCs in vitro possess a very limited proliferation potential, and the presence of stem cell aging has substantially restricted the effect together with the efficiency in clinical treatment. Recently, increasing attention has been paid to the connection between cellular aging and lysosomal acidification as new reports indicated that vacuolar H+-ATPase (v-ATPase) activity was altered and lysosomal pH was dysregulated in the process of cellular aging. Therefore, promoting lysosomal acidification might contribute to inhibition of cell senescence. Our previous studies showed that a novel small molecule, 3-butyl-1-chloro imidazo [1, 5-a] pyridine-7-carboxylic acid (SGJ), could selectively and sensitively respond to acidic pH with fast response (within 3 min), but whether SGJ can promote lysosomal acidification and inhibit senescence in BMSCs is unknown. Rat BMSCs were cultured based on our system that had been already documented. BMSCs were treated with SGJ and/or Bafilomycin-A1 (Baf-A1). The co-localization between SGJ and lysosomes was assessed by a confocal microscope. Acridine orange (AO) staining and the Lysosensor™ Green DND-189 reagents were used for indicating changes in lysosomal concentration of H+. Changes of senescence were detected by immunoblotting of p21 and senescence-associated beta-galactosidase (SA-β-gal) staining as well as immunofluorescence assay of senescence-associated heterochromatin foci (SAHF). Changes of autophagy were detected by immunoblotting of MAP1LC3 (LC3B) and SQSTM1 (p62). Cell proliferation was determined by flow cytometry. Cell viability was calculated by sulforhodamine B assay (SRB). The V0 proton channel of v-ATPase was knocked down by transfecting with its small interfering RNA (si-ATP6V0C). Our work showed that SGJ can promote lysosomal acidification and inhibit senescence in BMSCs. Firstly, SGJ and lysosomes were well co-located in senescent BMSCs with the co-localization coefficient of 0.94. Secondly, SGJ increased the concentration of H+ and the protein expression of lysosome-associated membrane protein 1 (LAMP1) and lysosome-associated membrane protein 2 (LAMP2). Thirdly, SGJ suppressed the expression of p21 in the senescent BMSCs and reduced SA-β-gal positive cells. Fourthly, SGJ promoted senescent BMSCs’ proliferation and protein level of LC3B but reduced the p62/SQSTM1 protein level. Furthermore, experimental group pretreated with 20 μM SGJ showed a stronger red fluorescent intensity, thinner cell morphology, less SA-β-gal positive cell, and less p21 protein level as well as higher cell viability in the presence of Baf-A1. Notably, ATP6V0C knockdown decreased the activity of v-ATPase and SGJ increased the concentration of H+. Our work showed that SGJ could inhibit senescence in BMSCs and protect lysosomes by promoting expression of LAMP1 and LAMP2. Meanwhile, SGJ could promote autophagy. Furthermore, our study also suggested that SGJ was a new Baf-A1 antagonist because SGJ could target and occupy the V0 proton channel of v-ATPase.

Postcontrast T1 Mapping for Differential Diagnosis of Recurrence and Radionecrosis after Gamma Knife Radiosurgery for Brain Metastasis.

Abstract: BACKGROUND AND PURPOSE: The differential diagnosis of radionecrosis and tumor recurrence in brain metastases is challenging. We investigated the diagnostic efficiency of postcontrast T1 mapping in solving this problem. MATERIALS AND METHODS: Between March 2016 and June 2017, fifty-six patients with brain metastases who underwent contrast-enhanced cerebral T1 mapping were recruited for this prospective study. The findings revealed new enhancement after gamma knife radiosurgery. The subjects were assigned to radionecrosis and recurrence groups based on follow-up (median, 11.5 months) and histopathologic results. T1 values of lesions 5 (T1 5min ) and 60 (T1 60min ) minutes after administration of contrast agent and their difference (T1 differ ) were compared between the 2 groups with the 2-tailed Mann-Whitney U test. Receiver operating characteristic curves were used to determine the optimum cutoff values for differential diagnosis. RESULTS: There were significant differences between the 2 groups in T1 5min , T1 60min , and T1 differ values ( P = .012, P = .004, and P 5min and T1 60min , T1 differ exhibited greater sensitivity and specificity ( P differ value for differential diagnosis was 71.1 ms (area under the curve = 0.97; 95% CI, 0.93–1.00), with sensitivity and specificity of 81.5% and 96.5%, respectively. CONCLUSIONS: Postcontrast T1 mapping is optimal for the differential diagnosis of radionecrosis and tumor recurrence. Among T1 parameters, T1 differ is the most powerful parameter for differential diagnosis. Advantages in terms of quantitative analysis and high resolution portend the wide use of postcontrast T1 mapping in the future.