Sublethal toxicity of graphene oxide in Caenorhabditis elegans under multi-generational exposure.

Nanomaterials have received increasing attentions owing to their potential hazards to the environment and human health; however, the multi-generational toxicity of graphene oxide under consecutive multi-generational exposure scenario still remains unclear. In the present study, Caenorhabditis elegans as an in vivo model organism was employed to explore the multi-generational toxicity effects of graphene oxide and the underlying mechanisms. Endpoints including development and lifespan, locomotion behaviors, defecation cycle, brood sizes, and oxidative response were evaluated in the parental generation and subsequent five filial generations. After continuous exposure for several generations, worms grew smaller and lived shorter. The locomotion behaviors were reduced across the filial generations and these reduced trends were following the impairments of locomotion-related neurons. In addition, the extended defecation cycles from the third filial generation were in consistency with the relative size reduction of the defecation related neuron. Simultaneously, the fertility function of the nematode was impaired under consecutive exposure as reduced brood sizes and oocytes numbers, increased apoptosis of germline, and aberrant expression of reproductive related genes ced-3, ced-4, ced-9, egl-1 and ced-13 were detected in exposed worms. Furthermore, the antioxidant enzyme, SOD-3 was significantly increased in the parent and filial generations. Thus, continuous multi-generational exposure to graphene oxide caused damage to the neuron development and the reproductive system in nematodes. These toxic effects could be reflected by indicators such as growth inhibition, shortened lifespan, and locomotion behavior impairment and induced oxidative response.

Validation of Quality of Life Instruments for Cancer Patients - Colorectal Cancer (QLICP-CR) in patients with colorectal cancer in Northeast China.

BACKGROUND: Measuring quality of life is important for cancer patients, but there are regional differences in age-standardized colorectal cancer incidence and mortality rates which may affect measurement. This study aimed to evaluate the reliability, validity and responsiveness of Quality of Life Instruments for Cancer Patients - Colorectal Cancer (QLICP-CR) in colorectal cancer patients in Northeast China, and assess its usefulness for evaluation of quality of life in these patients. METHODS: From November 2016 to January 2017, 152 patients with colorectal cancer from Liaoning Cancer Hospital & Institute were surveyed three times using QLICP-CR and the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) to measure their quality of life (on admission, 2-3 days later and at discharge). Reliability was evaluated by internal consistency and test-retest reliability. Validity was examined by item-domain correlation, criterion-related validity and factor construct validity analysis. Responsiveness was assessed using paired Student's t tests and calculating standardized response mean. RESULTS: Cronbach's α coefficient for QLICP-CR ranged from 0.62 to 0.93. Pearson correlation and intra-class correlation coefficients for QLICP-GM, the five domains and the total scale of QLICP-CR ranged from 0.74 to 0.91 and 0.74 to 0.90. The item-domain correlation analysis showed good convergent validity and discriminant validity. Correlation analysis of domain scores between FACT-C and QLICP-CR showed good criterion-related validity. Exploratory factor analysis revealed that nine and three principal components were extracted from items in the two modules of QLICP-CR, and the contribution rate of cumulative variance was 70.21 and 72.26%. There were significant differences in quality of life between the first and the third measurements, with standardized response mean values ranging from 0.30 to 0.81. CONCLUSIONS: The QLICP-CR was a reliable, valid and sensitive instrument to measure quality of life in colorectal cancer patients in Northeast China.

HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1/CDK2 signaling.

It is well accepted that HBx plays the major role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. However, little was known about its role in regulating long noncoding RNAs (lncRNAs), a large group of transcripts regulating a variety of biological processes including carcinogenesis in mammalian cells. Here we report that HBx upregulates UCA1 genes and downregulates p27 genes in hepatic LO2 cells. Further studies show that the upregulated UCA1 promotes cell growth by facilitating G1/S transition through CDK2 in both hepatic and hepatoma cells. Knock down of UCA1 in HBx-expressing hepatic and hepatoma cells resulted in markedly increased apoptotic cells by elevating the cleaved caspase-3 and caspase-8. More importantly, UCA1 is found to be physically associated with enhancer of zeste homolog 2 (EZH2), which suppresses p27Kip1 through histone methylation (H3K27me3) on p27Kip1 promoter. We also show that knockdown of UCA1 in hepatoma cells inhibits tumorigenesis in nude mice. In a clinic study, UCA1 is found to be frequently up-regulated in HBx positive group tissues in comparison with the HBx negative group, and exhibits an inverse correlation between UCA1 and p27Kip1 levels. Our findings demonstrate an important mechanism of hepatocarcinogenesis through the signaling of HBx-UCA1/EZH2-p27Kip1 axis, and a potential target of HCC.

[Antibacterial mechanism of sulforaphane on Escherichia coli].

OBJECTIVE: To investigate the antibacterial mechanism of sulforaphaneon (SFN) on Escherichia coli. METHODS: To determine membrane penetrability, changes of SDS-PAGE protein spectra, soluble protein and alkaline phosphatase and reducing sugar were determined. Cellular nucleic acid synthesis was detected by 4, 6- diamidino-2-phenylindole (DAPI) staining assay. RESULTS: SFN affected the membrane permeability of Escherichia coli. Ions and small molecules could leak out of the cells. But it did not destroy the membrane integrity directly. After 16 hours of treatment with SFN, the total contents of intracellular and extracellular proteins decreased by 42.5% and 17.6%, respectively, while the quantity of DNA and RNA reduced by 34.8% and 48.5% respectively. CONCLUSION: SFN can affect cell membrane permeability, material and energy metabolism and inhibit the synthesis of nucleic acid and protein.