Protection effect of sanguinarine on whole-body exposure of X radiation in BALB/c mice

To investigate the effects of sanguinarine (SAN) on acute radiation induced injury in mice, 45 mice were randomly divided into control, 10 Gy and SAN+10 Gy groups. Mice in the 10 Gy and SAN+10 Gy groups were exposed to single X-ray radiation with an accumulated dose of 10 Gy. Mice in the SAN+10 Gy group were administered intraperitoneally with 2.5 mg/kg body weight of SAN before radiation. Five days after radiation exposure, 5 mice from each group were sacrificed and samples of the small intestine, lung, spleen and liver were fixed for histopathological examinations. Compared with the 10 Gy group, radiation sickness was obviously delayed or attenuated in the SAN+10 Gy group. Survival analysis showed a significant difference between 2 radiation groups (PPara investigar os efeitos da sanguinarina (SAN) em lesões induzidas em ratos por radiação aguda, 45 ratos foram aleatoriamente divididos em grupo controle, grupo 10 Gy e grupo SAN+10 Gy. Os ratos dos grupos 10 Gy e SAN+10 Gy foram expostos à radiação de raio-X simples com uma dose acumulada de 10 Gy. Aos ratos do grupo SAN+10 Gy administraram-se, intraperitonealmente, 2.5 mg/kg de peso de SAN antes da radiação. Aos 5 dias de exposição à radiação, sacrificaram-se 5 ratos de cada grupo e retiraram-se amostras do intestino delgado, pulmões, baço e fígado para exames histopatológicos. Comparando com o grupo 10 Gy, a doença por radiação foi claramente atrasada e atenuada no grupo SAN+10 Gy. A análise de sobrevivência mostrou diferença significativa entre os dois grupos de radiação (

The Epigenetic Modifier PRDM5 Functions as a Tumor Suppressor through Modulating WNT/β-Catenin Signaling and Is Frequently Silenced in Multiple Tumors

BACKGROUND: PRDM (PRDI-BF1 and RIZ domain containing) proteins are zinc finger proteins involved in multiple cellular regulations by acting as epigenetic modifiers. We studied a recently identified PRDM member PRDM5 for its epigenetic abnormality and tumor suppressive functions in multiple tumorigeneses. METHODOLOGY/PRINCIPAL FINDINGS: Semi-quantitative RT-PCR showed that PRDM5 was broadly expressed in human normal tissues, but frequently silenced or downregulated in multiple carcinoma cell lines due to promoter CpG methylation, including 80% (4/5) nasopharyngeal, 44% (8/18) esophageal, 76% (13/17) gastric, 50% (2/4) cervical, and 25% (3/12) hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell lines. PRDM5 expression could be restored by 5-aza-2'-deoxycytidine demethylation treatment in silenced cell lines. PRDM5 methylation was frequently detected by methylation-specific PCR (MSP) in multiple primary tumors, including 93% (43/46) nasopharyngeal, 58% (25/43) esophageal, 88% (37/42) gastric and 63% (29/46) hepatocellular tumors. PRDM5 was further found a stress-responsive gene, but its response was impaired when the promoter was methylated. Ectopic PRDM5 expression significantly inhibited tumor cell clonogenicity, accompanied by the inhibition of TCF/β-catenin-dependent transcription and downregulation of CDK4, TWIST1 and MDM2 oncogenes, while knocking down of PRDM5 expression lead to increased cell proliferation. ChIP assay showed that PRDM5 bound to its target gene promoters and suppressed their transcription. An inverse correlation between the expression of PRDM5 and activated β-catenin was also observed in cell lines. CONCLUSIONS/SIGNIFICANCE: PRDM5 functions as a tumor suppressor at least partially through antagonizing aberrant WNT/β-catenin signaling and oncogene expression. Frequent epigenetic silencing of PRDM5 is involved in multiple tumorigeneses, which could serve as a tumor biomarker

Integration of Transcriptomics and Lipidomics Profiling to Reveal the Therapeutic Mechanism Underlying <i>Ramulus mori</i> (Sangzhi) Alkaloids for the Treatment of Liver Lipid Metabolic Disturbance in High-Fat-Diet/Streptozotocin-Induced Diabetic Mice

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder, with a global prevalence of 25%. Currently, there remains no approved therapy. Ramulus mori (Sangzhi) alkaloids (SZ-As), a novel natural medicine, have achieved comprehensive benefits in the treatment of type 2 diabetes; however, few studies have focused on its role in ameliorating hepatic lipid metabolic disturbance. Herein, the therapeutic effect and mechanism of SZ-As on a high-fat diet (HFD) combined with streptozotocin (STZ)-induced NAFLD mice were investigated via incorporating transcriptomics and lipidomics. SZ-As reduced body weight and hepatic lipid levels, restored pathological alternation and converted the blood biochemistry perturbations. SZ-A treatment also remarkedly inhibited lipogenesis and enhanced lipolysis, fatty acid oxidation and thermogenesis. Transcriptomics analysis confirmed that SZ-As mainly altered fatty acid oxidative metabolism and the TNF signaling pathway. SZ-As were further demonstrated to downregulate inflammatory factors and effectively ameliorate hepatic inflammation. Lipidomics analysis also suggested that SZ-As affected differential lipids including triglyceride (TG) and phosphatidylcholine (PC) expression, and the main metabolic pathways included glycerophospholipid, sphingomyelins and choline metabolism. Collectively, combined with transcriptomics and metabolomics data, it is suggested that SZ-As exert their therapeutic effect on NAFLD possibly through regulating lipid metabolism pathways (glycerophospholipid metabolism and choline metabolism) and increasing levels of PC and lysophosphatidylcholine (LPC) metabolites. This study provides the basis for more widespread clinical applications of SZ-As

Passenger Volume Prediction by a Combined Input-Output and Distributed Lag Model and Data Analytics of Industrial Investment

In order to sketch the transport infrastructure construction in an economy or a region, the government has to predict the passenger volume, under the local policy of industrial investment. In this paper, we propose a combined input-output and distributed lag prediction model of passenger volume in a province in P. R. China, under a certain policy of industrial investment called Silk Road Economic Belt. Specifically, the relationships between the passenger volume, GDP (gross domestic product), gross output, and transportation consumption are analyzed, and then the industrial development speed analysis and classification are used to calculate the average development speeds and the GDP contributions of 42 industries. Combining the input-output table, the provincial transportation consumption under the Silk Road Economic Belt policy is predicted, and the passenger volumes of the cities and the province in the future are predicted by the distributed lag models. Considering the uncertainty of the investment, the elastic ranges of the cities and the province’s passenger volumes are determined. The results show that the correlation between the passenger volume and transportation consumption is the highest, and it is equal to 0.975. In 2020, the passenger volume in Shaanxi is 1,641,305 thousands, and the error between the predicted value and the value obtained by summing the cities’ passenger volumes is smaller than 0.002%

Ergonomic Reliability Assessment for Passenger Car Interface Design Based on EWM-MADM and Human Cognitive Reliability Experiments

The ergonomic reliability assessment of interface design scheme for the passenger car is very practical to enhance driving safety performance. In addition, it can significantly reduce development costs and the development cycle of the new car. From the perspective of guiding the improvement of the central console interactive interface design of the passenger car, the most effective method to build the ergonomic reliability assessment method of the interactive interface is to evaluate and predict the human reliability objectively and subjectively and to design, feedback, and guide the design process of the ergonomic interface for the passenger car. Firstly, the questionnaire survey and the classification of ergonomic reliability analysis factors are analyzed to be put forward based on predecessors; the judgment layer factors and index layer factors of human-machine interaction interface in automobile central console are put forward. Secondly, entropy weight method (EWM) and multiple attribute decision-making (MADM) were used for objective evaluation and subjective evaluation, respectively. Thirdly, the interaction interfaces in central consoles of three different passenger cars are taken as examples; objective simulated experimental test based on entropy weight method and subjective scoring evaluation based on MADM were conducted, respectively. Besides, the objective evaluation and subjective evaluation are coupled by fuzzy comprehensive evaluation. Finally, to verify the effectiveness and rationality of the ergonomic reliability assessment method, human cognitive reliability experiments are made based on the data acquisition from the eye-tracking experiments