No abstract

Background Realistic, portable, and scalable lectures, cadaveric models, 2D atlases and computer simulations are being combined more frequently for teaching anatomy, which result in major increases in user satisfaction. However, although digital simulations may be more portable, interesting, or motivating than traditional teaching tools, whether they are superior in terms of student learning remain unclear. This paper presents a study in which the educational effectiveness of a virtual reality (VR) skull model is compared with that of cadaveric skulls and atlases. The aim of this study was to compare the results of teaching with VR to results of teaching with traditional teaching methods by administering objective questionnaires and perception surveys. Methods A mixed-methods study with 73 medical students was conducted with three different groups, namely, the VR group (N = 25), cadaver group (N = 25) and atlas group (N = 23). Anatomical structures were taught through an introductory lecture and model-based learning. All students completed the pre- and post-intervention tests, which comprised a theory test and an identification test. The theory test consisted of 18 multiple-choice questions, and the identification test consisted of 25 fill-in-the-blank questions. Results The participants in all three groups had significantly higher total scores on the post-intervention test than on the pre-intervention test; the post-intervention test score in the VR group was not statistically significantly higher than the post-intervention test score of the other groups (VR: 30 [IQR: 22–33.5], cadaver: 26 [IQR: 20–31.5], atlas: 28[IQR: 20–33]; p > 0.05). The participants in the VR and cadaver groups provided more positive feedback on their learning models than the atlas group (VR: 26 [IQR: 19–30], cadaver: 25 [IQR: 19.5–29.5], atlas: 12 [IQR: 9–20]; p < 0.001). Conclusions The skull virtual learning resource (VLR) was equally efficient as the cadaver skull and atlas in teaching anatomy structures. Such a model can aid individuals in understanding complex anatomical structures with a higher level of motivation and tolerable adverse effects.

The atypical E3 ubiquitin ligase RNF31 is highly expressed in human breast cancer, the most frequent neoplastic lethality among women. Here, RNF31 depletion in breast cancer cells in combination with global gene expression profiling revealed p53 (TP53) signaling as a potential RNF31 target. Interestingly, RNF31 decreased p53 stability, whereas depletion of RNF31 in breast cancer cells caused cell cycle arrest and cisplatin-induced apoptosis in a p53-dependent manner. Furthermore, RNF31 associated with the p53/MDM2 complex and facilitated p53 polyubiquitination and degradation by stabilizing MDM2, suggesting a molecular mechanism by which RNF31 regulates cell death. Analysis of publically available clinical data sets displayed a negative correlation between RNF31 and p53 target genes, including IGFBP3 and BTG1, consistent with RNF31 regulating p53 function in vivo as well. Together, our findings suggest RNF31 as a potential therapeutic target to restore p53 function in breast cancer.

Pifithrin-α (PFT-α) is a small molecule which has been widely used as a specific inhibitor of p53 transcription activity. However, its molecular mechanism of action remains unclear. PFT-α has also been described to display potent p53-independent activity in cells. In this study, we addressed the mechanism of action of PFT-α. We found that PFT-α failed to prevent the effects of Mdm2 inhibitor Nutlin-3 on cell cycle and apoptosis in several cancer cell lines. However, PFT-α rescued normal primary fibroblasts from growth inhibition by Nutlin-3. PFT-α displayed a very limited effect on p53-dependent transcription upon its activation by Nutlin-3. Moreover, PFT-α inhibitory effect on transcription was highly dependent on the nature of the p53 target gene. PFT-α attenuated post-translational modifications of p53 without affecting total p53 protein level. Finally, we found that PFT-α can decrease the level of intracellular reactive oxygen species through activation of an aryl hydrocarbon receptor (AHR)-Nrf2 axis in a p53-independent manner. In conclusion, PFT-α inhibits only some aspects of p53 function, therefore it should be used with extreme caution to study p53-dependent processes.

T cells and T cell receptors (TCRs) play pivotal roles in adaptive immune responses against tumors. The development of next-generation sequencing technologies has enabled the analysis of the TCRβ repertoire usage. Given the scarce investigations on the TCR repertoire in lung cancer tissues, in this study, we analyzed TCRβ repertoires in lung cancer tissues and the matched distant non-tumor lung tissues (normal lung tissues) from 15 lung cancer patients. Based on our results, the general distribution of T cell clones was similar between cancer tissues and normal lung tissues; however, the proportion of highly expanded clones was significantly higher in normal lung tissues than in cancer tissues (0.021% ± 0.002% vs. 0.016% ± 0.001%, P = 0.0054, Wilcoxon signed rank test). In addition, a significantly higher TCR diversity was observed in cancer tissues than in normal lung tissues (431.37 ± 305.96 vs. 166.20 ± 101.58, P = 0.0075, Mann-Whitney U test). Moreover, younger patients had a significantly higher TCR diversity than older patients (640.7 ± 295.3 vs. 291.8 ± 233.6, P = 0.036, Mann-Whitney U test), and the higher TCR diversity in tumors was significantly associated with worse cancer outcomes. Thus, we provided a comprehensive comparison of the TCR repertoires between cancer tissues and matched normal lung tissues and demonstrated the presence of distinct T cell immune microenvironments in lung cancer patients.

The activation of group I metabotropic glutamate receptor (group I mGlus) has been shown to produce neuroprotective or neurotoxic effects. In this study, we investigated the effects of N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, on group I mGlus activation in apoptosis of glial C6 and MN9D cell lines, and a rat model of Parkinson's disease (PD). We demonstrated that NAC protected against apoptosis through modulation of group I mGlus activity. In glial C6 cells, NAC promoted phosphorylation of ERK induced by (s)-3,5- dihydroxy-phenylglycine (DHPG), an agonist of group I mGlus. NAC enhanced the group I mGlus-mediated protection from staurosporine (STS)-induced apoptosis following DHPG treatment. Moreover, in rotenone-treated MN9D cells and PD rat model, NAC protected against group I mGlus-induced toxicity by compromising the decrease in phosphorylation of ERK, phosphorylation or expression level of TH. Furthermore, the results showed that NAC prohibited the level of ROS and oxidation of cellular GSH/GSSG (Eh) accompanied by activated group I mGlus in the experimental models. Our results suggest that NAC might act as a regulator of group I mGlus-mediated activities in both neuroprotection and neurotoxicity via reducing the oxidative stress, eventually to protect cell survival. The study also suggests that NAC might be a potential therapeutics targeting for group I mGlus activation in the treatment of PD.

Colorectal cancer (CRC) is one of the major types of cancer and causes of mortality worldwide, and it remains the third most common cause of cancer‑associated mortality worldwide. MicroRNAs (miRNAs) are a class of small RNAs, which have been shown to be associated with CRC. In the present study, an MTT assay and proliferating cell nuclear antigen (PCNA) protein examination assay were performed to detect RKO cell viability. Hoechst staining, and caspase‑3 activity and BrdU incorporation assays were performed to detect RKO cell apoptosis, respectively. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses were used to analyze the expression of cyclooxygenase‑2 (COX‑2). Western blot analysis was also used to analyze the expression of vascular endothelial growth factor (VEGF) and mitogen‑activated protein kinase (MAPK) signal molecules, including extracellular signal‑regulated kinase (ERK), p38 and c‑Jun N‑terminal kinase (JNK). The target genes of miR-125 were predicted using a double luciferase reporter gene assay. The results of the MTT assay showed that RKO cell viability was decreased by an miRNA-125 mimic and increased by the miRNA-125 inhibitor. The RKO cell viability was significantly correlated with the expression of PCNA. The migration of RKO cells was significantly downregulated in the miR-125 mimics‑transfected cells and upregulated in the miRNA-125 inhibitor‑transfected cells. The results of Hoechst staining and the caspase‑3 activity and BrdU incorporation assays showed that RKO cell apoptosis was increased following miRNA-125 mimic transfection and decreased following miRNA-125 inhibitor transfection. The results of the RT‑qPCR and western blot analysis showed that the expression of COX‑2 was increased in the miR-125 mimic‑transfected cells and decreased in the miR-125 inhibitor‑transfected cells. Using an online miRNA target prediction database, the double luciferase reporter gene assay showed that miR‑125 targeted and inhibited the expression of VEGF through target sites located in the 3' untranslated region of VEGF mRNA. In conclusion, the abnormal expression of miR‑125 was found to be closely associated with CRC. Therefore, miR‑125 may be a novel therapeutic target for CRC.

Members of the Mi14-3-3 gene family interact with target proteins that are widely involved in plant hormone signal transduction and physiology-related metabolism and play important roles in plant growth, development and stress responses. In this study, 14-3-3s family members are identified by the bioinformatic analysis of the mango (Mangifera indica L.) genome. The gene structures, chromosomal distributions, genetic evolution, and expression patterns of these genes and the physical and chemical properties and conserved motifs of their proteins are analysed systematically. The results identified 16 members of the 14-3-3 genes family in the mango genome. The members were not evenly distributed across the chromosomes, and the gene structure analysis showed that the gene sequence length and intron number varied greatly among the different members. Protein sequence analysis showed that the Mi14-3-3 proteins had similar physical and chemical properties and secondary and tertiary structures, and protein subcellular localization showed that the Mi14-3-3 family proteins were localized to the nucleus. The sequence analysis of the Mi14-3-3s showed that all Mi14-3-3 proteins contain a typical conserved PFAM00244 domain, and promoter sequence analysis showed that the Mi14-3-3 promoters contain multiple hormone-, stress-, and light-responsive cis-regulatory elements. Expression analysis showed that the 14-3-3 genes were expressed in all tissues of mango, but that their expression patterns were different. Drought, salt and low temperature stresses affected the expression levels of 14-3-3 genes, and different 14-3-3 genes had different responses to these stresses. This study provides a reference for further studies on the function and regulation of Mi14-3-3 family members.