A Potential Immune-Related miRNAs Regulatory Network and Corresponding Diagnostic Efficacy in Schizophrenia.

PURPOSE: Immune-related pathways actively participate in the progression of schizophrenia (SCZ), however, roles of immune-related miRNAs in SCZ are still unclear. METHODS: A microarray expression study was conducted to explored roles of immune-related genes in SCZ. Functional enrichment analysis by using "clusterProfiler" was used to identify molecular alterations of SCZ. Protein-protein interaction (PPI) network was constructed and helped core molecular factors identification. Based on The Cancer Genome Atlas (TCGA) database, clinical significances of hub immune-related genes in cancers were also been explored. Then, correlation analyses were used to determine immune-related miRNAs. We further validated that hsa-miR-1299 could be an effective diagnostic biomarker for SCZ via analyzing multi-cohorts' data and quantitative real-time PCR (qRT-PCR). RESULTS: A total of 455 mRNAs and 70 miRNAs that were differentially expressed between SCZ and control samples. Functional enrichment analysis based on differentially expressed genes (DEGs) hinted that immune-related pathways were significantly correlated with SCZ. Furthermore, a total of 35 immune-related genes that involved in disease onset and showed significant co-expressed relationships. Hub immune-related gene CCL4 and CCL22 are valuable in tumor diagnosis and survival prediction. Furthermore, we also identified 22 immune-related miRNAs that play important roles in this disease. An immune-related miRNAs-mRNAs regulatory network was constructed to provide miRNAs regulatory roles in SCZ. Core miRNAs expression status of hsa-miR-1299 were also validated in another cohort, which suggested its diagnostic performance for SCZ. CONCLUSIONS: Our study reports the downregulation of some miRNAs in the process of SCZ are important. Shared genomics characteristics between SCZ and cancers also provide novel insights for cancers. A significant alteration of hsa-miR-1299 expression is effective as biomarker for the diagnosis of SCZ, suggesting that this miRNA could be a specific biomarker.

Healthy sleep pattern reduce the risk of cardiovascular disease: A 10-year prospective cohort study.

OBJECTIVE: To identify the association between quantified sleep factors and the incidence of cardiovascular disease (CVD) through a 10-year prospective cohort study. METHODS: A total of 45,919 individuals were recruited in this population-based prospective study. The healthy sleep score was constructed by four sleep measures (sleep duration, insomnia symptoms, snoring and daytime sleepiness), which were collected by questionnaire. The hazard ratio (HR) and 95% confidence intervals (CIs) were calculated by the multivariate-adjusted Cox proportional hazards model. Restricted cubic spline analysis was used to examine the dose‒response relationships between healthy sleep scores and outcomes. RESULTS: During a median follow-up of 10.73 years (interquartile range: 10.08-11.72 years), 10,523 cases of total CVD incidence, 3766 cases of CHD, and 3967 cases of stroke incidence were documented. Our results found that participants who maintained four healthy sleep measures (including no insomnia, snoring, or frequent daytime sleepiness and sleeping 7-8 h/d) had a 12% (HR: 0.88, 95% CI: 0.84-0.93) and 16% (HR: 0.84, 95% CI: 0.78-0.92) lower risk of developing CVD and CHD, respectively, but not stroke. There was a dose‒response relationship between sleep scores and the risk of cardiovascular events. With an increasing healthy sleep score, the risk of cardiovascular events decreases. Compared to those with a sleep score of 0-1, participants with a score of 4 had 27% (HR: 0.73, 95% CI: 0.67-0.79), 25% (HR: 0.75, 95% CI: 0.65-0.87), and 24% (HR: 0.76, 95% CI: 0.66-0.86) reduced risks of CVD, CHD, and stroke, respectively. CONCLUSIONS: In this large prospective cohort study, a healthy sleep pattern effectively reduced the risk of CVD, CHD, and stroke.

CircFOXP1 alleviates brain injury after acute ischemic stroke by regulating STAT3/apoptotic signaling.

According to previous studies, circular RNAs (circRNAs) are involved in multiple pathological processes of acute ischemic stroke (AIS). However, the relationship between circFOXP1 and IS has not yet been reported. Here, we found that circFOXP1 expression was significantly decreased in the peripheral blood of AIS patients compared to controls and was associated with the severity and prognosis of AIS. Functionally, knockdown and overexpression of circFOXP1 promoted and inhibited apoptotic signaling, respectively, following oxygen-glucose deprivation/reperfusion (OGD/R) treatment in vitro. Adeno-associated virus (AAV)-mediated circFOXP1 overexpression attenuated neurological deficits and improved functional recovery after transient middle cerebral artery occlusion (tMCAO) treatment in vivo. Mechanistically, decreased QKI expression inhibited circFOXP1 biogenesis under hypoxic conditions. Decreased circFOXP1 expression accelerated signal transducer and activator of transcription 3 (STAT3) protein degradation by binding to and increasing STAT3 protein ubiquitination, ultimately aggravating brain injury after cerebral ischemia by activating apoptotic signaling. In summary, our study is the first to reveal that circFOXP1 alleviates brain injury after cerebral ischemia by regulating STAT3/apoptotic signaling, which provides a potentially novel therapeutic target for AIS.

Effects of PM2.5 pollution and single nucleotide polymorphisms of neurotrophin signaling pathway genes acting together on schizophrenia relapse.

PURPOSE: The objective of this study was to investigate the co-effect of long-term exposure to atmospheric particulate matter PM2.5 and single nucleotide polymorphisms on schizophrenia relapse. METHODS: A total of 332 patients with schizophrenia were recruited. Genotyping of eight SNPs for five genes along the neurotrophin signaling pathway was performed by the Sequenom Massarray technology platform. Based on the data from the monitoring stations, the PM2.5 level of each patient's residence was assessed by the inverse distance weighting method using Arc GIS software. Cox regression analysis was used to determine independent risk factors. The relationship between PM2.5 levels and the risk of schizophrenia relapse was evaluated using the restricted cubic spline (RCS) method. RESULTS: In this study, a total of 191 of 332 patients with schizophrenia relapsed with hospitalization. The risk of schizophrenia relapse was 13.62 (95% CI 8.29 to 22.37) in areas with PM2.5 concentrations of 48.43 to 75.35 µg/m3. The risk of schizophrenia relapse was 5.81 (95% CI 3.58-9.42, p < 0.001) and 13.62 (95% CI 8.29-22.37, p < 0.001) in the exposure categories Q3 and Q4, respectively, compared with Q1, and non-linear relationship between cumulative PM2.5 exposure and risk of schizophrenia relapse. A greater association was observed in the YWHAB gene polymorphic locus rs6031849 genotype TG (Hazard ratio 16.62, 95% CI 5.73 to 48.24). CONCLUSIONS: PM2.5 levels, YWHAB gene polymorphism locus rs6031849, and gender jointly influenced schizophrenia relapse, with long-term exposure to high levels of PM2.5 having the greatest effect on schizophrenia relapse.

Evaluation of Traditional Culture Teaching Efficiency by Course Ideological and Political Integration Lightweight Deep Learning.

With the development of society, China pays more and more attention to cultural education. The teaching method of introducing ideological and political content into cultural teaching plays an important role in improving the overall teaching quality. However, the traditional methods used to evaluate the quality of culture teaching, curriculum ideological, and political teaching have some problems, such as strong subjectivity and unrepresentative results. Firstly, this work analyzes the connotation of curriculum thought and politics. Secondly, a teaching quality evaluation model based on an improved lightweight convolutional neural network (CNN) is proposed, which mainly judges the students' recognition of teachers' content and teaching methods by identifying the students' expressions in the classroom. Finally, the students of a senior high school in Shanghai are selected as the survey object, and the current situation of ideological and political education (IPE) in the school curriculum is preliminarily understood by issuing a questionnaire; experiments are designed to test the performance of the model. The results show that most of the students in the school do not understand the connotation of IPE, and the teachers cannot accurately and deeply teach the relevant ideological and political knowledge to the students. About 73% and 82% of students prefer that teachers can mention life experience and social skills in class. More than 50% of the students are more willing to accept the course ideological and political activities in the form of lectures and competitions. This indirectly shows that the school lacks the above contents in the current course ideological and political teaching, the teaching method is relatively single, and cannot fully mobilize the enthusiasm of students. Further improvement is needed for these problems in the follow-up. The accuracy of expression recognition of this model is more than 2.9% higher than other algorithms, and the improvement effect of the model is remarkable. To sum up, this work fully understands the current teaching situation of the surveyed schools through questionnaire survey, and puts forward corresponding improvement suggestions. The effectiveness of this model is verified by designing experiments, which proves that it is suitable for the research of teaching quality evaluation.

Whole Transcriptome Sequencing Identified CircRNA Profiles and the Related Networks in Schizophrenia.

Schizophrenia (SCZ) is a complex psychiatric syndrome with uncertain etiology. This study aimed to uncover the expression profiles and related regulatory networks of circular RNA (circRNA) in SCZ. Whole transcriptome sequencing was performed to assess the expression profiles of circRNAs and microRNAs (miRNAs) in the peripheral blood of three patients with SCZ and three healthy controls. Five circRNAs were validated by quantitative real-time PCR (RT-qPCR). TargetScan, RNAhybrid, and miRanda were performed to predict the target miRNAs of the top 10 dysregulated circRNAs. MiRTarBase was applied to predict the target mRNAs of miRNAs to construct circRNA-miRNA-mRNA (ceRNA) networks. CatRAPID and StarBase were used to predict the target RNA-binding proteins (RBPs) of circRNAs to construct circRNA-RBP networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the potential functions of the maternal genes of circRNAs and target mRNAs. In total, 450 circRNAs and 160 miRNAs were found to be significantly differentially expressed, with hsa_circ_0003999 and hsa_circ_0030042 being significantly different between patients with SCZ and healthy controls (P < 0.05). The PI3K-AKT, MAPK, and cell cycle pathways were predicted to be associated with SCZ. GO analysis showed that focal adhesion was related to SCZ. The ceRNA networks, especially hsa_circ_0006151/hsa-miR-4685-3p/ZBTB16, hsa_circ_0000008/hsa-miR-1976/ZBTB16, and the hsa_circ_0007963/hsa-miR-3127-3p/UBE2K axes have the greatest probability of being involved in the pathophysiology of SCZ. The RBP networks, FXR1, FXR2, DGCR8, XRN2, FMR1, and QKI were the RBPs associated with SCZ. In conclusion, the circRNAs, ceRNAs, and RBP network expression patterns and related pathways indicate the potential role of circRNAs in the pathogenesis and development of SCZ.

Antiproliferative activities of Garcinia bracteata extract and its active ingredient, isobractatin, against human tumor cell lines.

In our cell based screening of antitumor ingredients from plants, the EtOH extract of Garcinia bracteata displayed antiproliferative effect against human lung adenocarcinoma A549 cells, human breast cancer MCF-7 cells, and human prostate cancer PC3 cells. Phytochemical investigation of this active extract produced nine ingredients, and their structures were established by analysis of MS and NMR spectra. Antiproliferative evaluation of isolated ingredients on A549, MCF-7 and PC3 cells indicated that a xanthone named isobractatin (1) exhibited potent antiproliferative activity against the above three human cancer cell lines with IC50 values ranging from 2.90 to 4.15 µM. Treatment of PC3 cells with 1 led to an enhancement of the cell apoptosis, and arrested cell cycle in the G0/G1 phase. The G0/G1 phase cycle-related proteins analysis showed that the expressions of cyclins D1 and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activations of Bax, caspases 3 and 9, and by inhibition of Bcl-2. Our combined data illustrated that isobractatin (1) was the antiproliferative ingredient of G. bracteata against three human cancer cell lines, which exerted its antiproliferatrive effect via cell cycle arrest and induction of apoptosis.

[Antiproliferative effect of cycloartane-type triterpenoid from myrrh against human prostate cancer cells].

OBJECTIVE: To investigate the antiproliferative effect of cycloartan-24-ene-1alpha, 2alpha, 3beta-triol from Myrrh against human prostate cancer cells. METHODS: Morphological changes of compound-treated human prostate PC3 cells were determined by staining cells with Hoechst. The cell cycle progression and apoptosis were evaluated using flow cytometry assay. Apoptosis related protein levels were analyzed using Western blotting. RESULTS: Treatment of PC3 cells with cycloartan-24-ene-1alpha,2alpha,3beta-triol caused an increase ratio of apoptotic cells, which was verified by flow cytometry. It was also found that cycloartan-24-ene-1alpha,2alpha, 3beta-triol arrested cell cycle at the G0/G1 phase. Apoptosis related proteins, such as BCL-2, BAX, Caspase-3 and Caspase-9 were changed. CONCLUSION: These observes data indicate that cycloartan-24-ene-1alpha,2alpha,3beta-triol inhibit the proliferation of PC3 cells via induction of apoptosis and cell cycle arrest.

[Biotransformation of cycloartane-type triterpenoid from myrrh].

OBJECTIVE: To study the biotransformation of cycloartan-24-ene-1alpha,2alpha, 3beta-triol isolated from myrrh and find new antitumor bioactive cycloartane-type derivatives. METHODS: Fourteen microbial strains were cultured in potato medium at 27.8 degrees C for 7 days. The strain of Penicillium janthinellum was selected for preparative transform assay, and cultured in potato medium at 27.8 degrees C for 10 days. The medium was extracted by EtOAc, and then EtOAc layer was purified by the silica gel column chromatography. The product was structurally elucidated by MS and NMR spectra, and their anti-proliferative effects against human prostate cancer PC3 and DU145 cells were evaluated using MTT assay. RESULTS: The substrate was transformed to two new hydroxyl substituted triterpenoids, with a yield of 21.15%; The products displayed anti-proliferative effect against PC3 and DU145 cells with IC50 values of 14.5 micromol/L and 27.8 micromol/L, respectively. CONCLUSION: Cycloartane-type triterpenoid can be bio-transformed by Penicillium janthinellum, and leading to the isolation of two new hydroxyl substituted derivatives.