Carbon Nanostructure-Based DNA Sensor Used for Quickly Detecting Breast Cancer-Associated Genes.

The early diagnosis of breast cancer highly relies on the detection of mutant DNA at low concentrations. Förster resonance energy transfer (FRET) quenching may offer a solution to quickly detect a small amount of single-strand DNA (ssDNA) through the combination of nanomaterials with special luminescence and unique structures of DNA double helix structure. Here, carbon quantum dots (CDs) modified with Capture ssDNA act as the FRET donor which interact with the two-dimensional fluorescence quencher, i.e., graphene oxide nanosheets (GO), to detect breast cancer-associated Target ssDNA at a low concentration. CDs bioconjugated with the designed Capture ssDNA (named CDs-Capture ssDNA) have the maximum fluorescence intensity (Imax) at the emission (λem) = 510 nm. The fluorescence of CDs-Capture ssDNA is quenched, while they interact with GO due to the π-π* interaction between ssDNA and GO. In the presence of Target ssDNA, the Imax is restored because of the stronger interaction between Target ssDNA and CDs-Capture ssDNA through the hydrogen bond. The restored fluorescence intensity of CDs has a linear relationship with the concentration of Target ssDNA from 0.25 to 2.5 µM with a detection limit around 0.24 µM. The selectivity of the sensing system has been further evaluated by testing the 3-base mismatched and non-base matched in which efficient restoration of photoluminescence of the sensing system cannot be observed. This carbon nanostructure-based DNA sensing system offers a user-friendly and quick detection of single-strand DNA at lower concentration.

Design and Development of Nanomaterial-Based Drug Carriers to Overcome the Blood-Brain Barrier by Using Different Transport Mechanisms.

Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood-brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.

Active Compound of Pharbitis Semen (Pharbitis nil Seeds) Suppressed KRAS-Driven Colorectal Cancer and Restored Muscle Cell Function during Cancer Progression.

Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer (CRC) is notorious to target with drugs and has shown ineffective treatment response. The seeds of Pharbitis nil, also known as morning glory, have been used as traditional medicine in East Asia. We focused on whether Pharbitis nil seeds have a suppressive effect on mutated KRAS-driven CRC as well as reserving muscle cell functions during CRC progression. Seeds of Pharbitis nil (Pharbitis semen) were separated by chromatography and the active compound of Pharbitis semen (PN) was purified by HPLC. The compound PN efficiently suppressed the proliferation of mutated KRAS-driven CRC cells and their clonogenic potentials in a concentration-dependent manner. It also induced apoptosis of SW480 human colon cancer cells and cell cycle arrest at the G2/M phase. The CRC related pathways, including RAS/ERK and AKT/mTOR, were assessed and PN reduced the phosphorylation of AKT and mTOR. Furthermore, PN preserved muscle cell proliferation and myotube formation in cancer conditioned media. In summary, PN significantly suppressed mutated KRAS-driven cell growth and reserved muscle cell function. Based on the current study, PN could be considered as a promising starting point for the development of a nature-derived drug against KRAS-mutated CRC progression.

Self-illumination of Carbon Dots by Bioluminescence Resonance Energy Transfer.

Carbon-dots (CDs), the emerging fluorescent nanoparticles, show special multicolor properties, chemical stability, and biocompatibility, and are considered as the new and advanced imaging probe in replacement of molecular fluorophores and semiconductor quantum dots. However, the requirement of external high power light source limits the application of fluorescent nanomaterials in bio-imaging. The present study aims to take advantage of bioluminescence resonance energy transfer mechanism (BRET) in creating self-illuminating C-dots. Renilla luciferase (Rluc) is chosen as the BRET donor molecule. Conjugation of Renilla luciferase and C-dots is necessary to keep their distance close for energy transfer. The optimal condition for achieving BRET is investigated by studying the effects of different factors on the performance of BRET, including the type of conjugation, concentration of carbon dots, and conjugation time. The linear relationship of BRET efficiency as a function of the amount of C-dots in the range of 0.20-0.80 mg/mL is observed. The self-illuminating carbon dots could be applied in bioimaging avoiding the tissue damage from the external high power light source.

The health-related quality of life of nursing workers: A cross-sectional study in medical institutions.

AIMS: This study aimed to evaluate the health-related quality of life of nursing workers and influential factors. BACKGROUND: Nursing workers are under great occupational stress. However, few population-level studies of nursing workers' health conditions have been reported from China. DESIGN: This was a cross-sectional study conducted in 12 medical institutions in east China between January and March 2015. METHODS: Social-demographic information, nursing workers' work-related information and health-related quality of life using the Chinese (mainland) version of the Short Form 36 health survey were collected by a self-administrated questionnaire. RESULTS: Nursing workers reported significantly lower scores of the vitality, mental health dimensions, and mental component summary of the Short Form 36 survey compared with general population reference values. They scored significantly higher for five other dimensions and comparably for the physical role dimension. Pre-job training, families' positive attitudes to their job, and good relationships with clients were positively related with nursing workers' mental well-being. CONCLUSION: To promote nursing workers' mental health, compulsory work-related training, voluntary psychological counselling, and targeted legislation are needed.

Integration of Nanomaterials and Bioluminescence Resonance Energy Transfer Techniques for Sensing Biomolecules.

Bioluminescence resonance energy transfer (BRET) techniques offer a high degree of sensitivity, reliability and ease of use for their application to sensing biomolecules. BRET is a distance dependent, non-radiative energy transfer, which uses a bioluminescent protein to excite an acceptor through the resonance energy transfer. A BRET sensor can quickly detect the change of a target biomolecule quantitatively without an external electromagnetic field, e.g., UV light, which normally can damage tissue. Having been developed quite recently, this technique has evolved rapidly. Here, different bioluminescent proteins have been reviewed. In addition to a multitude of bioluminescent proteins, this manuscript focuses on the recent development of BRET sensors by utilizing quantum dots. The special size-dependent properties of quantum dots have made the BRET sensing technique attractive for the real-time monitoring of the changes of target molecules and bioimaging in vivo. This review offers a look into the basis of the technique, donor/acceptor pairs, experimental applications and prospects.

Cordyceps militaris Grown on Germinated Soybean Suppresses KRAS-Driven Colorectal Cancer by Inhibiting the RAS/ERK Pathway.

Cordyceps militaris is a commonly used medicinal mushroom containing various therapeutic effects such as anti-inflammatory, anti-allergic, and anti-cancer activities. This study examined whether Cordyceps militaris on germinated soybeans (GSC) has a suppressive effect on a v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer which is notorious for its un-druggable features and the ineffectiveness of conventional therapies against it. GSC extract was prepared and its proximate composition and amino acids were analyzed. The suppressive effects were investigated with the KRAS-driven colorectal cancer cell-line, SW480. SW480 proliferation, clonogenic potential, apoptosis, and the RAS/extracellular signal-regulated kinase (ERK) pathway under the GSC treatment were analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, flow cytometry, and Western blot, respectively. An in vivo experiment with the SW480 xenograft mouse model was performed. As a result, GSC suppressed cell proliferation by inducing the apoptosis of KRAS-driven colorectal cancer cells and inhibited clonogenic capabilities. The decrease of KRAS and ERK phosphorylation was detected by Western blot. Tumor growth was significantly suppressed when GSC was introduced to the tumor-xenograft mouse model. In conclusion, GSC suppressed KRAS-driven colorectal cancer growth both in vitro and in vivo, and can be used as an alternative or simultaneous approach in colorectal cancer therapy.

Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate After Single-dose Administration in Healthy Korean Male Subjects.

PURPOSE: Tedizolid phosphate is a next-generation oxazolidinone prodrug that is transformed into the active moiety tedizolid. Its indication is acute bacterial skin and skin structure infections caused by gram-positive species, including methicillin-resistant Staphylococcus aureus. Although tedizolid phosphate has been marketed in Korea, no data on the pharmacokinetic (PK) properties or tolerability of tedizolid phosphate in Korean subjects are available. This study was designed to evaluate the PK properties, oral bioavailability, and tolerability with a single-dose oral and intravenous administration of tedizolid phosphate in healthy Korean male subjects. METHODS: A block-randomized, double-blind, placebo-controlled, single-dose study was conducted in 3 groups (200, 400, and 600 mg; 10 subjects in each group). In the second part of the study, subjects from the 200-mg group received administration orally and intravenously (1-hour infusion) via 2-way crossover for the evaluation of absolute bioavailability. There was a 7-day washout period between treatments in the absolute bioavailability part of the study. Serial blood samples for PK analysis were collected for up to 72 hours. Tolerability was assessed by analysis of adverse events. FINDINGS: Thirty healthy Korean subjects completed the study and were included in the PK and tolerability analyses. Tedizolid phosphate was rapidly converted into tedizolid. After a single oral dose, the Tmax of tedizolid was observed to be 1.5 to 2.5 hours, and the plasma concentration-time curve of tedizolid showed a 2-phase elimination pattern, with a half-life of ~11 hours. Dose-dependent increases were observed in the AUClast value (29,441-78,062 µg · h/L) and in the Cmax value (2679-6980 µg/L) with the administration of tedizolid phosphate 200 to 600 mg PO. The absolute bioavailability of tedizolid was 95.2% (90% CI, 92.7%-97.8%) in the 200-mg administration group. There were no serious adverse events or clinically significant changes in the tolerability assessment. IMPLICATIONS: Tedizolid phosphate at doses of up to 600 mg was well-tolerated in these healthy Korean male subjects. Tedizolid shows dose linearity with oral administration, and no dose adjustment of tedizolid phosphate 200 mg would be needed when switching administration routes. ClinicalTrials.gov identifier: NCT02097043.