Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

Early-life exposure to PM2.5 leads to ASD-like phenotype in male offspring rats through activation of PI3K-AKT signaling pathway.

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms.

Bioinformatics analysis proposes a possible role for long noncoding RNA MIR17HG in retinoblastoma.

BACKGROUND: Retinoblastoma (RB) is the most common prevalent intraocular malignancy among infants and children, particularly in underdeveloped countries. With advancements in genomics and transcriptomics, noncoding RNAs have been increasingly utilized to investigate the molecular pathology of diverse diseases. AIMS: This study aims to establish the competing endogenous RNAs network associated with RB, analyse the function of mRNAs and lncRNAs, and finds the relevant regulatory network. METHODS AND RESULTS: This study establishes a network of competing endogenous RNAs by Spearman correlation analysis and prediction based on RB patients and healthy children. Enrichment analyzes based on Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes are conducted to analyze the potential biological functions of lncRNA and mRNA networks. Weighted gene co-expression network analysis (WGCNA) is employed to identify gene cluster modules exhibiting the strongest correlation with RB. The results indicate a significant correlation between the lncRNA MIR17HG (R = .73, p = .02) and the RB phenotype. ceRNA networks reveal downstream miRNAs (hsa-mir-425-5p and hsa-mir455-5p) and mRNAs (MDM2, IPO11, and ITGA1) associated with MIR17Hg. As an inhibitor of the p53 signaling pathway, MDM2 can suppress the development of RB. CONCLUSION: In conclusion, lncRNAs play a role in RB, and the MIR17HG/hsa-mir-425-5p/MDM2 pathway may contribute to RB development by inhibiting the p53 signaling pathway.

Integrative Bioinformatics Analysis of mRNA Expression Profiles of Mice to Explore the Key Genes Involved in Crim1 Mutation-Induced Congenital Cataracts.

Crim1 has been implicated in cataracts in mice and is of great importance in the development of the eye in both humans and mice. Therefore, we aimed to clarify how Crim1 mutations affect lens development and the molecular mechanism of cataracts in mice through comprehensive bioinformatics analysis. The microarray chip was downloaded from the GEO database to obtain the gene expression profile data set. Differentially expressed genes (DEGs) were screened using the limma package. GO and KEGG analyses of DEGs were performed using the DAVID database. Then, we established the protein-protein interaction (PPI) network in Cytoscape. Next, we used MCODE to analyze the data. We obtained 750 DEGs in total, including 407 upregulated DEGs and 343 downregulated DEGs. GO analysis showed that the DEGs were mainly related to biological processes, such as apoptosis, cell translation and the immune system. KEGG analysis showed that the enriched functions and pathways were related to the processing and presentation of ribosomes, lysosomes, and antigens. We identified 18 HUB genes, among which four core genes, C1qa, C1qb, C1qc, and Cd74, were closely related to congenital cataracts induced by Crim1 mutation. This study reveals the molecular pathogenesis of congenital cataracts induced by Crim1, and this information is expected to facilitate clinical genetic testing, molecular diagnosis, prognosis, and individualized chemotherapy for congenital cataracts (CC).

[Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats].

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

Exosomes in the pathogenesis and treatment of ocular diseases.

Exosomes have diverse functions and rich content and are involved in intercellular communication, immune regulation, viral infection, tissue regeneration, and the occurrence, development and metastasis of tumours. Notably, various stem cell-derived exosomes are expected to become new therapeutic approaches for inflammatory diseases and tumours and have good clinical application prospects. However, few studies have examined exosomes in ophthalmic diseases. Therefore, based on the functions of exosomes, this paper summarizes progress in the possible use of exosomes as treatment for specific ophthalmic diseases, aiming to determine the pathogenesis of exosomes to achieve more effective clinical diagnosis and treatment of these diseases.

Large reductions in pesticides made possible by use of an insect-trapping lamp: a case study in a winter wheat-summer maize rotation system.

BACKGROUND: Increasing attention is being paid to physical methods to control pests such as insect trapping. In order to examine how pesticides can reasonably be combined with the use of an insect-trapping lamp and by how much this can reduce the amount of pesticide used, five treatments were applied to a winter wheat-summer maize rotation system in eastern China: a treatment in which only pesticides were used; a treatment with only insect-trapping lamps; insect-trapping lamps plus one application of pesticides; insect-trapping lamps plus two applications of pesticides; insect-trapping lamps plus three applications of pesticides. RESULTS: The results showed that, when pesticides were reduced by 25-35%, the insect-trapping lamps controlled the insect population well and yields were not decreased but were actually increased, with pesticides being applied only at 2 days before winter wheat planting, at winter wheat flowering and at the big flare stage of summer maize. Reducing pesticides by 35-65% had no adverse effect on crop yields, and thus had the potential to reduce the costs of pest control and produce the greatest economic benefit. When no pesticides were used in the insect-trapping lamp control area, the annual yield was still >15 t hm-2 . CONCLUSION: If pesticides are used in a timely fashion and at the appropriate stage, their use may be greatly reduced with the help of an insect-trapping lamp. © 2018 Society of Chemical Industry.

[Progress in the studies on antitumor natural product ecteinascidin-743].

The alkaloid ecteinascidin-743, isolated from the marine tunicate Ecteinascidia turbinata, binds to DNA and induces cytotoxic effects in several tumors. The drug is being codeveloped by Pharma Mar and Ortho Biotech. In May 2001 and October 2003, it was granted orphan drug status by the European Commission for soft tissue sarcoma and ovarian cancer, respectively. This paper reviews its research progress, including chemical synthesis, in vitro studies and mechanism of action, antitumor activity in vivo, toxicity, pharmacokinetics, and clinical studies.

Cytotoxic alkaloids from the roots of Tylophora atrofolliculata.

Four new phenanthroindolizidine alkaloids, tylophoridicines C-F, together with three known ones, R-(+)-deoxytylophorinidine, tylophorinine and tylophorinidine, were isolated from the roots of Tylophora atrofolliculata. The structures were determined on the basis of spectral evidence. These alkaloids exhibited cytotoxic activity in vitro on HCT-8 cell (with IC50 values in the range 0.083 to 18.99 microM) and KB cell (in the range 3.56 to 18.22 microM) lines.

[Synthesis and drug resistant reversal activities of taxane-like multi-drug resistant reversal agents].

AIM: To design and synthesize a series of new taxoids with a 5-O-sidechain, and to test the multi-drug resistant reversal activity of these compound on KB/V200 cells which is 180 times more resistant to vincristine. METHODS: Using Sinenxan A as a common synthetic starting material, three different types of 5-O-sidechain molecules were synthesized through different route. For type I compounds, 14-acetoxy of Sinenxan A was selectively removed by hydrolysis, xanthation and reduction with tributyltin; A C-10-oxo group was introduced by PCC oxidation; 5-O-acetyl group was selectively removed by potassium tert-butoxide and finally the side chain was introduced by acylating with the corresponding acid. For type II compounds, 5-O-sidechain was introduced to the 5-deacetyl Sinenxan A which was obtained by selective hydrolysis with tBuOK. For type III compounds, 9-acetoxy group was introduced, then 5-OH was left free by thorough hydrolysis and reacetylation. Acylation at 5-position, the final product was obtained. Structure of the compounds have been confirmed by FABMS and 2DNMR. The activity of the compounds in vitro was tested on KB/V200 resistant cell line using MTT method. RESULTS: Nine compounds showed resistant reversal activity and enhancing the cytotoxicity of vicristine against KB/V200 cells. Compounds I2, I3, I4 restored the sensitivity of KB/V200 towards vicristine to a level of IC50 at 1 x 10(-8) mol.L-1 which is better than the positive control Verapamil. CONCLUSION: The drug resistant reversal activity of taxane derivatives can be affected by substitution at different positions and the length of side chains of Sinenxan A. It is worthy to be further studied.