GCS overexpression is associated with multidrug resistance of human HCT-8 colon cancer cells

<p>Abstract</p> <p>Purpose</p> <p>Multidrug resistance is one of the main impediments to the successful treatment of colon cancer. Glucosylceramide synthase (GCS) which is related to multidrug resistance (MDR) can reduce the level of ceramide and can help cells escape from the ceramide-induced cell apoptosis. However, the underlying mechanism is still unclear.</p> <p>Methods</p> <p>The cell proliferation and cell toxicity were measured with Cell Counting Kit-8 (CCK-8). The mRNA levels of GCS and MDR1 were detected by semiquantitative reverse transcription-PCR amplification, the protein levels of GCS, caspase-3 and P-gp proteins were indicated by Western blotting. The apoptosis rates of cells were measured with flow cytometry.</p> <p>Results</p> <p>The relative mRNA levels of GCS in HCT-8, HCT-8/VCR, HCT-8/VCR- sh-mock and HCT-8/VCR-sh-GCS were 71.4 ± 1.1%, 95.1 ± 1.2%, 98.2 ± 1.5%, and 66.6 ± 2.1% respectively. The mRNA levels of MDR1 were respectively 61.3 ± 1.1%, 90.5 ± 1.4%, 97.6 ± 2.2% and 56.1 ± 1.2%. The IC50 of Cisplatin complexes were respectively 69.070 ± 0.253 μg/ml, 312.050 ± 1.46 μg/ml, 328.741 ± 5.648 μg/ml, 150.792 ± 0.967 μg/ml in HCT-8, HCT-8/VCR, HCT-8/VCR-sh-mock and HCT-8/VCR-sh-GCS. The protein levels of caspase-3 were 34.2 ± o.6%, 93.0 ± 0.7%, 109.09 ± 0.7%, 42.7 ± 1.3% respectively. The apoptosis rates of cells were 8.77 ± 0.14%, 12.75 ± 0.54%, 15.39 ± 0.41% and 8.49 ± 0.23% respectively.</p> <p>Conclusion</p> <p>In conclusion, our research indicated that suppression of GCS restores the sensitivity of multidrug resistance colon cancer cells to drug treatment.</p

Psychopathy and Decision-Making: Antisocial Factor Associated With Risky Decision-Making in Offenders

Psychopathy is a personality development disorder increasing the risk of antisocial behavior. Studies on the relationship between psychopathy and decision-making have received limited attention and the result of studies is mixed. A present study examines whether or not the different factors of psychopathy are related to decision-making under risk and ambiguity in offenders and how they are related. Also, the study investigates whether general intelligence is associated with decision-making or moderates the relationship between psychopathy and decision-making. The results showed that only antisocial factor of psychopathy significantly correlates with Game of Dice Task (GDT) risky selections, but there no general relation between psychopathy and Iowa Gambling Task (IGT) performance. Lastly, general intelligence neither is related to decision-making under risk and ambiguity nor moderates the relationship between decision-making and psychopathy. The study results show that antisocial factor of psychopathy was associated with decision-making under risk rather than ambiguity. Our results also suggest that the antisocial factor of psychopathy was more related to executive dysfunction in offenders

The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas

<p>Abstract</p> <p>Background</p> <p>14-3-3 sigma (σ) promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown.</p> <p>Methods</p> <p>We investigated the 14-3-3σ expression in a series of 302 vulvar squamous cell carcinomas using immunohistochemistry and its associations with clinicopathological factors and clinical outcome.</p> <p>Results</p> <p>In cytoplasm, nucleus and cytoplasm/nucleus of vulvar carcinomas high 14-3-3σ protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% and 25% of the cases, respectively. High level of 14-3-3σ in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (<it>p </it>= 0.001, <it>p </it>= 0.002 and <it>p </it>= 0.001, respectively) and deep invasion (<it>p </it>= 0.01, <it>p </it>= 0.001 and <it>p </it>= 0.007, respectively). Variations of 14-3-3σ protein expression were not associated to disease-specific survival.</p> <p>Conclusion</p> <p>Our results indicate that 14-3-3σ may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3σ protein. Neither cytoplasmic nor nuclear level of 14-3-3σ expression was associated with prognosis.</p

Decreased expression of GST pi is correlated with a poor prognosis in human esophageal squamous carcinoma

Background Glutathione S-transferase pi (GST pi) is a subgroup of GST family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Expression patterns of GST pi have been studied in several carcinomas and its down-regulation was implicated to be involved in malignant transformation in patients with Barrett's esophagus. However, neither the exact role of GST pi in the pathogenesis nor its prognostic impact in squamous esophageal carcinoma is fully characterized. Methods Immunohistochemistry was used to investigate GST pi expression on 153 archival squamous esophageal carcinoma specimens with a GST pi monoclonal antibody. Statistic analyses were performed to explore its association with clinicopathological factors and clinical outcome. Results The GST pi expression was greatly reduced in tissues of esophageal carcinomas compared to adjacent normal tissues and residual benign tissues. Absent of GST pi protein expression in cytoplasm, nuclear and cytoplasm/nucleus was found in 51%, 64.7% and 48% of all the carcinoma cases, respectively. GST pi deficiency in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to poor differentiation (p < 0.001, p < 0.001 and p < 0.001, respectively). UICC stage and T stage were found significantly correlated to negative expression of GST pi in cytoplasm (p < 0.001 and p = 0.004, respectively) and cytoplasm/nucleus (p = 0.017 and p = 0.031, respectively). In univariate analysis, absent of GST pi protein expression in cytoplasm, nucleus and cytoplasm/nucleus was significantly associated with a shorter overall survival (p < 0.001, p < 0.001 and p < 0.001, respectively), whereas only GST pi cytoplasmic staining retained an independent prognostic significance (p < 0.001) in multivariate analysis. Conclusions Our results show that GST pi expression is down regulated in the squamous esophageal carcinoma, and that the lack of GST pi expression is associated with poor prognosis. Therefore, deficiency of GST pi protein expression may be an important mechanism involved in the carcinogenesis and progression of the squamous esophageal carcinoma, and the underlying mechanisms leading to decreased GST pi expression deserve further investigation

Nurses’ job preferences on the internet plus nursing service program: a discrete choice experiment

Abstract Background The Internet Plus Nursing Service (IPNS) is being instigated in all provincial-level regions throughout China, in which registered nurses (with more than five years of experience from qualified medical institutions) will provide services to those in their communities or homes after receiving online applications. The growing shortage of human resources in nursing is a critical issue for this project, so effective policies for recruiting and retaining nurses are critical. Objective This study aims to pinpoint the significant job characteristics that play a crucial role in shaping the job decisions of sharing nurses in the IPNS program, and to estimate the strength of job attributes. Methods A discrete choice experiment (DCE) was used to assess job attributes influencing sharing nurses’ preferences. A qualitative design, including in-depth interview and focus interview methods, was conducted to determine the inclusion of attributes. The final included six attributes were: work modes, duration per visit, income per visit, personal safety, medical risk prevention, and refresher training. This study was conducted at 13 hospitals in Guangdong Province, China, from April to June 2022, and a total of 220 registered sharing nurses participated in the survey. The multinomial logit model explored attributes and relative valued utility. Preference heterogeneity is explored via latent class analysis (LCA) models. Results A total of 220 participants answered the questionnaire. Income was the most influential characteristic of a sharing nursing position, followed by personal safety management, duration per visit, medical risk prevention, and refresher training, and nurses’ preferences differed among different types of classes. Conclusions Sharing nurses place most value on income and personal safety with career-related decisions, which indicates an urgent need to develop complete security for personal safety. This study can be helpful to decision-makers in the Chinese government