A Fluorescent Furan-based Probe with Protected Functional Groups for Highly Selective and Non-Toxic Imaging of HT-29 Cancer Cells and 4T1 Tumors.

Most of the previously reported fluorescent organic probes for cancer cell and tumor imaging have significant limitations including chemical toxicity, structural instability, low Stokes shift value, and the inability for selective accumulations in tumors during in vivo imaging. To overcome the mentioned challenges, we synthesized the fluorescent probes with protected polar functional groups to enhance the non-toxicity nature and increase the selectivity toward tumors. In addition, the structural rigidity of the fluorescent probes was increased by embedding aromatic rings in the probe structure. This issue enables us to obtain ultrabright cell images due to enhanced fluorescence quantum yield (ΦFL) values. After synthesis and spectral characterizations, the applicability of two furan-based and imidazole-based fluorescent probes ( abbreviated as DCPEF and DBPPI, respectively) was investigated for ultrabright in vitro and in vivo imaging of cancer cells. The probe DCPEF shows the ΦFL value of 0.946 and the Stocks shift of 86 nm. In addition, probe DBPPI offers the ΦFL value of 0.400 and a Stocks shift of 150 nm. The MTT colorimetric cytotoxicity assay showed that probe DCPEF has minimal effects against HT-29 (cancer) and Vero (normal) cells. The probe DCPEF produced ultrabright fluorescence images from HT-29 cells. In addition, in vivo imaging of cancer cells showed that probe DCPEF selectively accumulates in the 4T1 tumor in mice. The spectral and chemical stability, minimal cytotoxicity, significant Stokes shift, and high degree of selectivity for tumor cells during in vivo imaging make DCPEF an appropriate candidate to be used as a standard probe for cancer cell imaging.

Reinvigorating aza-Michael reactions under ionic liquid catalysis: a greener approach.

Cholinium α-amino carboxylates, which debuted in the ionic liquid arena over a decade ago, exhibit superior stability and suitable physical properties relative to other RTILs. Although synthetic pursuits in such media, leveraging their dual role as solvents and catalysts, have been scarce so far, we herein illustrate their catalytic advantage in aza-Michael reactions in terms of low loading, acceleration and improved yields with respect to conventional conditions and other imidazolium-based ILs. These highly structured salts most likely act through multiple and cooperative non-covalent interactions. These mechanistic features have also been investigated through high-level computational analyses as well.

Ring Opening Polymerization Used for the Production of VOC Free High-Performance Ecofriendly Novel PBZ/PDA/CeO2 Nanocomposites.

This study analyzed the fabrication and characterization of polybenzoxazine/polydopamine/ceria as tertiary nanocomposites. To this end, a new benzoxazine monomer (MBZ) was fabricated based on the well-known Mannich reaction of naphthalene-1-amine, 2-tert-butylbenzene-1,4-diol and formaldehyde under ultrasonic-assisted process. Polydopamine (PDA) was used as dispersing polymer nanoparticles and surface modifier for CeO2 by in-situ polymerization of dopamine with the assistance of ultrasonic waves. Then, nanocomposites (NC)s were manufactured by in-situ route under thermal conditions. The FT-IR and 1H-NMR spectra confirmed the preparation of the designed MBZ monomer. The FE-SEM and TEM results showed the morphological aspects of prepared NCs and illustrated the distribution of CeO2 NPs in the polymer matrix. The XRD patterns of NCs showed the presence of crystalline phases of nanoscale CeO2 in an amorphous matrix. The TGA results reveal that the prepared NCs are classified as thermally stable materials.

Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome.

Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanisms driving CdLS phenotypes are not understood. In addition to its canonical role in sister chromatid cohesion, cohesin is implicated in the spatial organization of the genome. Here, we investigate the transcriptome of CdLS patient-derived primary fibroblasts and observe the downregulation of genes involved in development and system skeletal organization, providing a link to the developmental alterations and limb abnormalities characteristic of CdLS patients. Genome-wide distribution studies demonstrate a global reduction of NIPBL at the NIPBL-associated high GC content regions in CdLS-derived cells. In addition, cohesin accumulates at NIPBL-occupied sites at CpG islands potentially due to reduced cohesin translocation along chromosomes, and fewer cohesin peaks colocalize with CTCF.

Network Analysis of Lung Transcriptomics Reveals a Distinct B-Cell Signature in Emphysema.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by a combination of airways disease (bronchiolitis) and parenchymal destruction (emphysema), whose relative proportion varies from patient to patient. OBJECTIVES: To explore and contrast the molecular pathogenesis of emphysema and bronchiolitis in COPD. METHODS: We used network analysis of lung transcriptomics (Affymetrix arrays) in 70 former smokers with COPD to compare differential expression and gene coexpression in bronchiolitis and emphysema. MEASUREMENTS AND MAIN RESULTS: We observed that in emphysema (but not in bronchiolitis) (1) up-regulated genes were enriched in ontologies related to B-cell homing and activation; (2) the immune coexpression network had a central core of B cell-related genes; (3) B-cell recruitment and immunoglobulin transcription genes (CXCL13, CCL19, and POU2AF1) correlated with emphysema severity; (4) there were lymphoid follicles (CD20(+)IgM(+)) with active B cells (phosphorylated nuclear factor-κB p65(+)), proliferation markers (Ki-67(+)), and class-switched B cells (IgG(+)); and (5) both TNFRSF17 mRNA and B cell-activating factor protein were up-regulated. These findings were by and large reproduced in a group of patients with incipient emphysema and when patients with emphysema were matched for the severity of airflow limitation of those with bronchiolitis. CONCLUSIONS: Our study identifies enrichment in B cell-related genes in patients with COPD with emphysema that is absent in bronchiolitis. These observations contribute to a better understanding of COPD pathobiology and may open new therapeutic opportunities for patients with COPD.

Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that likely includes clinically relevant subgroups. OBJECTIVES: To identify subgroups of COPD in ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) subjects using cluster analysis and to assess clinically meaningful outcomes of the clusters during 3 years of longitudinal follow-up. METHODS: Factor analysis was used to reduce 41 variables determined at recruitment in 2,164 patients with COPD to 13 main factors, and the variables with the highest loading were used for cluster analysis. Clusters were evaluated for their relationship with clinically meaningful outcomes during 3 years of follow-up. The relationships among clinical parameters were evaluated within clusters. MEASUREMENTS AND MAIN RESULTS: Five subgroups were distinguished using cross-sectional clinical features. These groups differed regarding outcomes. Cluster A included patients with milder disease and had fewer deaths and hospitalizations. Cluster B had less systemic inflammation at baseline but had notable changes in health status and emphysema extent. Cluster C had many comorbidities, evidence of systemic inflammation, and the highest mortality. Cluster D had low FEV1, severe emphysema, and the highest exacerbation and COPD hospitalization rate. Cluster E was intermediate for most variables and may represent a mixed group that includes further clusters. The relationships among clinical variables within clusters differed from that in the entire COPD population. CONCLUSIONS: Cluster analysis using baseline data in ECLIPSE identified five COPD subgroups that differ in outcomes and inflammatory biomarkers and show different relationships between clinical parameters, suggesting the clusters represent clinically and biologically different subtypes of COPD.