Dicyanoisophorone-based near-infrared fluorescent probe with large Stokes shift for the monitoring and bioimaging of hypochlorite.

Hypochlorite (ClO-), as one of reactive oxygen species (ROS), is closely linked to various illnesses and is essential for the proper functioning of immune system. Hence, monitoring and assessing ClO- levels in organisms are extremely important for the clinical diagnosis of ClO--related disorders. In this study, a novel ClO--selective fluorescent probe, DCP-ClO, was synthesized with dicyanoisophorone-xanthene unit as parent fluorophore, which displayed excellent selectivity towards ClO-, near-infrared emission (755 nm), large Stokes shift (100 nm), real-time response to ClO-, high sensitivity (LOD = 3.95 × 10-8 M), and low cytotoxicity. The recognition mechanism of DCP-ClO towards ClO- was confirmed to be a typical ICT process by HPLC-MS, HR-MS, 1H NMR and theoretical calculations. Meanwhile, DCP-ClO demonstrated remarkable efficacy in monitoring ClO- levels in water samples and eye-catching ability in imaging endogenous/exogenous ClO- in living organisms, which verified its potential as a powerful tool for the recognition of ClO- in complex biological systems.

New Near-Infrared Fluorescence Imaging Platform with Large Stokes Shift for Carboxylesterase 2 Detection in Thyroid Cancer and Inflammatory Diseases Diagnosis.

Development of new near-infrared fluorophores is one of the eternal themes in the field of biosensing and biological imaging. In this work, we constructed a novel fluorophore platform MOR by replacing methylindole of hemicyanine fluorophore (CyR) with benzoxazole to acquire better fluorescence characteristics. Based on the platform, a near infrared (NIR) fluorescent probe MOR-CES2 was synthesized for the specific "off-on" response to carboxylesterase 2 (CES2). The probe exhibited excellent properties including near-infrared emission (735 nm), large Stokes shift (105 nm), high sensitivity (LOD, 0.3 ng/mL), and rapid response (15 min). The successful application of MOR-CES2 in biological imaging of CES2 in mice with thyroid cancer and inflammatory bowel disease demonstrated that the probe could identify cancer cells and tissues and sensitively respond to inflammation. The results proved the potency of MOR-CES2 as an efficient imaging tool to assist in the surgical resection of CES2-related tumors.

GDF11 upregulation independently predicts shorter overall-survival of uveal melanoma.

Growth differentiation factor 11 (GDF11), is a member of the transforming growth factor-beta (TGF-ß) superfamily and bone morphogenetic protein (BMP) subfamily. In this study, we aimed to assess the expression profile of GDF11, its prognostic value in terms of OS, as well as the potential mechanisms leading to its dysregulation in uveal melanoma. A retrospective study was conducted using our primary data and genetic, clinicopathological and overall survival (OS) data from the Cancer Genome Atlas-Uveal Melanoma (TCGA-UVM). Results showed that GDF11 expression was significantly higher in tumor tissues compared with that in adjacent normal tissues. High GDF11 expression was associated with uveal melanoma in advanced stages (IV), epithelioid cell dominant subtype, as well as extrascleral extension. Univariate analysis showed that older age, epithelioid cell dominant, with extrascleral extension and increased GDF11 expression were associated with unfavorable OS. Multivariate analysis confirmed that GDF11 expression was an independent prognostic indicator of unfavorable OS (HR: 1.704, 95%CI: 1.143-2.540, p = 0.009), after adjustment of age, histological subtypes and extrascleral extension. Among the 80 cases of uveal melanoma, only 3 cases had low-level copy gain (+1) and 2 cases had heterozygous loss (-1). No somatic mutations, including SNPs and small INDELs were observed in GDF11 DNA. The methylation of these four CpG sites had weakly (cg22950598 and cg23689080), moderately (cg09890930), or strongly (cg05511733) negative correlation with GDF11 expression. In addition, the patients with high methylation of these four sites had significantly better OS compared to the group with low methylation. Based on these findings, we infer that methylation modulated GDF11 expression might be a valuable prognostic biomarker regarding OS in uveal melanoma.

Clinical efficacy of intravitreal ranibizumab in early and mid-idiopathic choroidal neovascularization.

Background. To compare visual outcomes and spectral-domain optical coherence tomography results following intravitreal ranibizumab treatment for early and mid-idiopathic choroidal neovascularization (ICNV). Methods. This retrospective, case-controlled study examined 44 patients with ICNV in one eye initially treated with intravitreal ranibizumab (0.5 mg). Further intravitreal treatments were administered as necessary. Patients were divided into two groups according to disease duration, that is, ≤3 months or 3-6 months (early and mid-groups), and the data were compared. Results. All patients completed at least 12 months of follow-up. Significant differences were observed between the groups in best-corrected visual acuity and in central macular thickness (CMT) reduction at all five follow-up visits. At the last follow-up (12 months), 19 early group eyes (79.1%) and 10 mid group eyes (50.0%) had statistically significant visual gains of >15 early treatment diabetic retinopathy study (ETDRS) letters (χ (2) = 4.130, P = 0.042). The mean number of injections was significantly higher (P = 0.0001) in the mid group (2.53 ± 1.76) than in the early group (1.22 ± 1.01). Conclusions. Early intravitreal ranibizumab for ICNV can result in better visual prognoses, more obvious decreases in CMT, and fewer injections.

Comparison of clinical efficacy of intravitreal ranibizumab with and without triamcinolone acetonide in macular edema secondary to central retinal vein occlusion.

PURPOSE: To compare visual outcomes and spectral-domain optical coherence tomography results following treatment with intravitreal ranibizumab (IVR) or IVR combined with intravitreal triamcinolone acetonide (IVTA) for macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: This prospective, case-controlled study examined 57 eyes (57 patients) with ME secondary to CRVO, which were treated with IVR (0.5 mg, n = 30 eyes) or IVR (0.5 mg) and IVTA (1 mg, n = 27 eyes) as the initial therapy. Further intravitreal treatment was administered as necessary. RESULTS: All 57 patients completed at least 6 months of follow-up. At baseline, mean ( ± standard error) best-corrected visual acuity (BCVA) was 45.8 ± 23.2 letters in the IVR group and 47.3 ± 19.3 letters in the IVR + IVTA group (p = 0.790). Significant improvement in BCVA over baseline was observed in both groups at all six study visits (IVR group: p = 0.0003, 0.0001, 0.0018, 0.0145, 0.0107, 0.005; IVR + IVTA group: p = 0.0001, 0.0001, 0.0004, 0.0068, 0.0007, 0.0002), with no significant BCVA differences between groups. Significant reduction in mean central subfield thickness, compared with baseline, was also observed in both groups at all six study visits (IVR group, p = 0.0001; IVR + IVTA group, p = 0.0001), with no significant difference between groups in the magnitude of macular thickness reduction. The mean number of injections was significantly higher (p = 0.0001) in the IVR group (4.23 ± 0.56) than in the IVR + IVTA group (3.42 ± 0.41). CONCLUSIONS: Treating ME secondary to CRVO with IVR or IVR + IVTA had similar effects on central macular thickness and BCVA in patients with ME secondary to CRVO over a 6-month follow-up period. The mean number of intravitreal injections was higher in the IVR group than in the IVR + IVTA group.