Integrative transcriptome and single-cell sequencing technology analysis of the potential therapeutic benefits of oleanolic acid in liver injury and liver cancer.

BACKGROUND: Oleanolic acid has important hepatoprotective effects and inhibits liver tissue carcinogenesis. The aim of this study was to investigate the mechanism of action of oleanolic acid in inhibiting liver injury and liver cancer. METHOD: In this study, we applied differential gene analysis and gene enrichment analysis to identify the targets of oleanolic acid for the treatment of liver injury. And this study also applied Cibersort and GSVA methods to investigate the targets of oleanolic acid in liver injury. Based on oleanolic acid targets, we explored the major targets and further explored the role of the major targets in liver cancer. This study used the oncoPredict and the TIDE algorithm to predict the effect of oleanolic acid on drug resistance. Finally, the binding effect of oleanolic acid to relevant targets was explored using molecular docking techniques. RESULT: In this study, oleanolic acid was found to inhibit liver injury and promote liver regeneration mainly by promoting elevated expression of HMOX1. Oleanolic acid can inhibit oxidative stress and promotes Ferroptosis in liver injury. In liver cancer, we identified that the main target of oleanolic acid is HMOX1 and HDAC1. And we determined that HMOX1 promotes Ferroptosis in liver cancer. This reduced the sensitivity of liver cancer to targeted therapies and immunotherapy. Molecular docking showed high binding of oleanolic acid to HDAC1 and HMOX1. CONCLUSIONS: Oleanolic acid is an antioxidant by promoting high expression of HMOX1 and promotes the development of Ferroptosis in liver cancer and liver injury.

The use of a technology-assisted and teacher-supervised online discussion platform to promote academic progress in blended embryology courses.

BACKGROUND: Students' engagement with learning materials and discussions with teachers and peers before and after lectures are among the keys to the successful implementation of blended programs. Mixed results have been reported by previous studies on blended learning. This study evaluated the effectiveness of embedding a teacher-supervised online discussion platform in a blended embryology course in terms of its impact on students' capabilities to handle difficult and cognitively challenging tasks. METHODS: Two forms of blended learning were investigated and compared in this study. Students in the control group (n = 85) learned online materials before each class, followed by classroom instruction and activities in which face-to-face discussion and communication between students were encouraged. Students in the experimental group (n = 83) followed a similar procedure with an additional teacher-supervised online discussion platform to guide, supervise and evaluate their learning progress. All participants were first-year medical students in clinical medicine at Dalian Medical University who had enrolled in 2017. All participants took the final exam to test their learning outcomes. RESULTS: The embryology grades of students in the experimental group were significantly higher than those of students in the control group (p = 0.001). Additionally, the scores of students in the experimental group on questions with a high difficulty level (p = 0.003) and questions assessing high-order cognitive skills (p = 0.003) were higher than those of students in the control group; the effect size was moderate (η2 > 0.05). CONCLUSIONS: In blended embryology courses, compared with learner-led and face-to-face discussion, the teacher-supervised online discussion platform has great potential to enable students to achieve higher grades and solve difficult and cognitively challenging tasks.

Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma.

Background: Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoma of central nervous system, which is often found in immunocompromised patients. The common clinical treatment of PCNSL is methotrexate (MTX) and whole brain radiation therapy. With the development of tumour immunology research, the tumour microenvironment of PCNSL is characterised by abnormal expression of different immune signature molecules and patients with PCNSL may benefit from tumour immunotherapy. Methods: In our research, RNA-seq data from 82 PCNSL patients were collated by mining the microarray data from the GEO database. All samples were classified into three types related to tumour immune response by the Cibersort algorithm and consistent clustering. Differential analysis of genes was used to uncover 2 sets of differential genes associated with tumour immunity. The ICI scores of each sample were obtained by PCA algorithm, and the relationship between ICI scores and immune checkpoint expression, immunotherapy and drug sensitivity was investigated. Genes associated with ICI scores and their functional characteristics were investigated by WGCNA analysis and PPI analysis, based on the ICI scores of each sample. Results: The tumour microenvironment in PCNSL has a greater relationship with the tumour immune response. ICI scores obtained from 375 differential genes were associated with multiple immune responses in PCNSL. PCNSL patients with higher ICI scores had a better tumour microenvironment and were sensitive to immunotherapy and some small molecule drug. This study also identified 64 genes associated with ICI scores, which may serve as important therapeutic and prognostic targets for PCNSL. Conclusion: The presence of multiple immunosuppressive responses in the tumour microenvironment of PCNSL which suggested that improving the immune function of PCNSL patients through immunotherapy and targeted therapies can be an effective treatment for PCNSL. And the ICI score and associated genes may also provide a better predictor of the clinical use of immunotherapy.

Transcriptome analysis of adipocytokines and their-related LncRNAs in lung adenocarcinoma revealing the association with prognosis, immune infiltration, and metabolic characteristics.

Lung adenocarcinoma (LUAD) is amongst the major contributors to cancer-related deaths on a global scale. Adipocytokines and long non-coding RNAs (lncRNAs) are indispensable participants in cancer. We performed a pan-cancer analysis of the mRNA expression, single nucleotide variation, copy number variation, and prognostic value of adipocytokines. LUAD samples were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Simultaneously, train, internal and external cohorts were grouped. After a stepwise screening of optimized genes through least absolute shrinkage and selection operator regression analysis, random forest algorithm,, and Cox regression analysis, an adipocytokine-related prognostic signature (ARPS) with superior performance compared with four additional well-established signatures for survival prediction was constructed. After determination of risk levels, the discrepancy of immune microenvironment, immune checkpoint gene expression, immune subtypes, and immune response in low- and high-risk cohorts were explored through multiple bioinformatics methods. Abnormal pathways underlying high- and low-risk subgroups were identified through gene set enrichment analysis (GSEA). Immune-and metabolism-related pathways that were correlated with risk score were selected through single sample GSEA. Finally, a nomogram with satisfied predictive survival probability was plotted. In summary, this study offers meaningful information for clinical treatment and scientific investigation.