An MTH1-targeted nanosystem for enhanced PDT via improving cellular sensitivity to reactive oxygen species.

Herein, we developed a strategy to attack the cancer cell defense system against reactive oxygen species to improve photodynamic therapy efficacy with a Ce6@MSN@MTH1 siRNA nanosystem, which was demonstrated to improve cellular sensitivity to reactive oxygen species through suppressing MTH1 protein in cancer cells.

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC.

BACKGROUND/AIMS: Programmed death ligand1(PD-L1) plays a role in the development and progression of non-small cell lung cancer (NSCLC). This study aimed to identify miRNA(s) that are responsible for regulation of expression of PD-L1 in NSCLC, and to investigate the role of PD-L1 in regulation of the cell cycle in NSCLC. METHODS: We predicted the target miRNA of PD-L1, which was miR-140, using the online tools TargetScan and miBase. In NSCLC cells obtained from clinical specimens, in addition to A549 and NCI-H1650 cell cultures, western blots were used to detect the level of expression of proteins, while real-time PCR was used to determine the level of expression of PD-L1, miR-140, cyclin E, and ß-actin. Transfection with miR-140 mimics, miR-140 inhibitors, and PD-L1 siRNA were conducted using commercial kits. To determine whether miR-140 directly binds PD-L1, a luciferase reporter gene with wild type or mutated PD-L1 was used. Cell viability was measured with the MTT assay, and PI staining was used for cell cycle analysis. RESULTS: We found low expression of miR-140 and high expression of PD-L1 and cyclin E in NSCLC cells. Over-expression of miR-140 suppressed the expression of PD-L1 by directly binding its 3' UTR, and was also associated with decreased expression of cyclin E and inhibition of cellular proliferation in A549 and NCI-H1650 cells. Inhibition of PD-L1, in the absence of manipulations to miR-140, also decreased the expression of cyclin E. CONCLUSION: We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.

Efficient Two-Photon Fluorescent Probe for Nitroreductase Detection and Hypoxia Imaging in Tumor Cells and Tissues.

Hypoxia plays an important role in tumor progression, and the development of efficient methods for monitoring hypoxic degree in living systems is of great biomedical importance. In the solid tumors, the nitroreductase level is directly corresponded with the hypoxic status. Many one-photon excited fluorescent probes have been developed for hypoxia imaging in tumor cells via the detection of nitroreductase level. However, two-photon excited probes are more suitable for bioimaging. In this work, a two-photon probe 1 for nitroreductase detection and hypoxic status monitoring in living tumor cells and tissues was reported for the first time. The detection is based on the fact that the nitro-group of probe 1 could be selectively reduced to an amino-group by nitroreductase in the presence of reduced NADH, following by a 1,6-rearrangement-elimination to release the fluorophore, resulting in the enhancement of fluorescence. The probe exhibited both one-photon and two-photon excited remarkable fluorescence enhancement (∼70-fold) for nitroreductase, which afforded a high sensitivity for nitroreductase, with a detection limit of 20 ng/mL observed. Moreover, the applications of the probe for fluorescent bioimaging of hypoxia in living cells and two-photon bioimaging in tissues were carried out, with tissue-imaging depths of 70-160 µm observed, which demonstrates its practical application in complex biosystems.

A rhodamine-appended water-soluble conjugated polymer: an efficient ratiometric fluorescence sensing platform for intracellular metal-ion probing.

Thewater-soluble CP was conjugatedwith a rhodamine spirolactam for the first time to develop a new FRET-based ratiometric fluorescence sensing platform(CP 1) for intracellular metal-ion probing. CP 1 exhibits excellent water-solubility with twowell-resolved emission peaks, which benefit ratiometric intracellular imaging applications.

[Development of safety climate measurement at workplace: validity and reliability assessment].

OBJECTIVE: To develop a measurement of safety climate at workplace and assess its validity and reliability. METHODS: According to the theory of preventive safety culture model, a scale including 7 dimensions of 27 items was developed. 342 workers were selected from among all workers of an artificial board factory and were investigated with the developed scale. Occupational accidents were recorded during the past year. Factor analysis, association validation and inter-item consistency test were applied to assess the scale validity and reliability. RESULTS: After the deletion of 6 items, 21 items composed the safety climate scale, which was loaded on 7 common factors: safety competence and consciousness, safety communication, organizational environment, management support, danger judgment, safety control measure and safety training. The cumulative contribution reached to 70.50%. All item communities (common factor variance) were above 0.6 except one item was 0.595. ANOVA showed that occupational accidents were associated with the safety climate score on total, danger judgment and safety control measure dimension (P < 0.05). There existed significant correlation between the safety climate total score and dimension scores (P < 0.01), the correlation coefficients were 0.700, 0.728, 0.705, 0.703, 0.354, 0.571 and 0.485 respectively. The safety climate scale total Cronbach's alpha coefficient, half-split Spearman-Brown coefficient, theta coefficient and omega coefficient indicated that the safety climate scale had good inter-item consistency among items. CONCLUSION: The measurement of safety climate at workplace is developed. It has good reliability and valid.