Search

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.

Abstract 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.

Objective: Investigate the effects of Hexokinase-3 on the proliferation, cell cycle, migration and immunologic invasion of RKO and HCT116. Methods: The expression levels of HK3 in tumor and normal colon samples were analyzed by bioinformatics. RKO and HCT116 were transfected with the control group (si-NC) and interference group HK3(si-HK3#1, si-HK3#2). CCK-8, Flow cytometry, wound healing and Transwell were used to examine the effects of interference with HK3 on the proliferation, cell cycle and migration of RKO and HCT116 cells. The expression levels of vimentin and E-cadherin, which are related to epithelialmesenchymal transition(EMT), were detected by Western blot. Results: HK3 is associated with infiltration of multiple immune cells and co-expression with multiple immune checkpoints in colorectal cancer. Compared with the Control group (si-NC), the protein expression level of HK3 in interference group (si-HK3#1, si-HK3#2) was significantly decreased(P<0.05);the proliferation and migration of RKO and HCT116 cells were significantly inhibited(P<0.05);the cell cycle of RKO and HCT116 cells was arrested in S phase(P<0.05) and the expression of E-cadherin protein was increased, but the expression of vimentin protein was inhibited(P <0.05). Conclusion: HK3 affects the level of immunologic invasion of colon cancer. Interference with HK3 inhibits the proliferation, cell cycle and migration of colon cancer cells by inhibiting EMT behavior. [ABSTRACT FROM AUTHOR]