Epigenetic changes may account for the doubled risk to develop schizophrenia in individuals exposed to famine in utero. We therefore investigated DNA methylation in a unique sample of patients and healthy individuals conceived during the great famine in China. Subsequently, we examined two case-control samples without famine exposure in whole blood and brain tissue. To shed light on the causality of the relation between famine exposure and DNA methylation, we exposed human fibroblasts to nutritional deprivation. In the famine-exposed schizophrenia patients, we found significant hypermethylation of the dual specificity phosphatase 22 (DUSP22) gene promoter (Chr6:291687-293285) (N = 153, p = 0.01). In this sample, DUSP22 methylation was also significantly higher in patients independent of famine exposure (p = 0.025), suggesting that hypermethylation of DUSP22 is also more generally involved in schizophrenia risk. Similarly, DUSP22 methylation was also higher in two separate case-control samples not exposed to famine using DNA from whole blood (N = 64, p = 0.03) and postmortem brains (N = 214, p = 0.007). DUSP22 methylation showed strong genetic regulation across chromosomes by a region on chromosome 16 which was consistent with new 3D genome interaction data. The presence of a direct link between famine and DUSP22 transcription was supported by data from cultured human fibroblasts that showed increased methylation (p = 0.048) and expression (p = 0.019) in response to nutritional deprivation (N = 10). These results highlight an epigenetic locus that is genetically regulated across chromosomes and that is involved in the response to early-life exposure to famine and that is relevant for a major psychiatric disorder.
The paper proposes a method to measure the mean velocity of solid particles based on the spatial filtering effect of the electrostatic sensor. To determine the relationship between the spatial frequency characteristics of the sensor and solid particle velocity, a general formula is derived by analyzing quantitatively the spatial filtering characteristics of the electrostatic sensor along with the accepted assumptions. The effects of the geometric parameters of the sensor, particle velocity distribution, particle concentration distribution over the cross-section of a pneumatic pipeline, particle size, particle material type and frequency resolution on particle velocity measurement accuracy are also discussed in detail. Experiments are performed on a bench-scale gravity-fed particle flow experimental rig to test the performance of the velocity measurement system. The off-line experimental results show that the system repeatability is within ±5% over the velocity range of 2–6 m s−1 for concentrations of solid particles in the range of 0.5–6.0%.
The Chinese National Twin Registry (CNTR) currently includes data from 61 566 twin pair from 11 provinces or cities in China. Of these, 31 705, 15 060 and 13 531 pairs are monozygotic, same‐sex dizygotic and opposite‐sex dizygotic pairs, respectively, determined by opposite sex or intrapair similarity. Since its establishment in 2001, the CNTR has provided an important resource for analysing genetic and environmental influences on chronic diseases especially cardiovascular diseases. Recently, the CNTR has focused on collecting biologic specimens from disease‐concordant or disease‐discordant twin pairs or from twin pairs reared apart. More than 8000 pairs of these twins have been registered, and blood samples have been collected from more than 1500 pairs. In this review, we summarize the main findings from univariate and multivariate genetic effects analyses, gene–environment interaction studies, omics studies exploring DNA methylation and metabolomic markers associated with phenotypes. There remains further scope for CNTR research and data mining. The plan for future development of the CNTR is described. The CNTR welcomes worldwide collaboration.
Aim To investigate the effects of a bioactive glass with a high proportion of phosphorus (BG‐hP) on the repair and regeneration of dental pulps in rats under an inflammatory microenvironment. Methodology Human dental pulp cells (hDPCs) stimulated with 1 μg mL−1 lipopolysaccharide (LPS) were co‐cultured with 0.1 mg mL−1 BG‐hP. Cell proliferation was detected by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyltetrazolium bromide (MTT) assays. The expression of inflammation‐related genes and odontogenic differentiation‐related genes was determined by real‐time PCR. Alizarin red staining was used to detect the formation of mineralized nodules. Coronal pulp tissues of rat molars were stimulated with 10 mg mL−1 LPS and then treated with BG‐hP. The expression of inflammation‐related genes in pulp tissue was determined by real‐time PCR. Haematoxylin‐eosin staining and Masson staining were performed to observe the inflammatory response and mineralized matrix formation, after subcutaneous implantation in nude mice, at 3 days and 4 weeks, respectively. Analysis of variance was performed to measure statistical significance (P < 0.05). Results BG‐hP significantly reduced expression of interleukin‐6 (IL‐6) and IL‐8 and significantly upregulated the expression of IL‐10, IL‐4 and transforming growth factor‐β1 of the LPS‐stimulated hDPCs (P < 0.05). BG‐hP significantly inhibited the initial cell number (P < 0.05), but the hDPCs stimulated by LPS and co‐cultured with BG‐hP maintained the same proliferation rate as the untreated hDPCs. BG‐hP significantly promoted the expression of dentine matrix protein‐1 and dentine sialophosphoprotein and the mineralization capacity of the LPS‐stimulated hDPCs (P < 0.05). Furthermore, BG‐hP significantly downregulated the expression of Il‐6 and reduced the inflammatory response of the LPS‐stimulated pulp tissue 3 days after subcutaneous implantation (P < 0.05). Four weeks after subcutaneous implantation, BG‐hP induced the formation of a continuous layer of dentine‐like structure with dentinal tubules and polarizing odontoblast‐like cells aligned along it in the LPS‐stimulated pulp tissue. Conclusion The present preliminarily results demonstrated that the bioactive glass with a high proportion of phosphorus inhibited the inflammatory response and promoted the formation of a pulp‐dentine complex in a rat experimental model. This study provides a foundation for the construction of materials with the dual functions of exerting anti‐inflammatory effects and promoting tissue regeneration to meet the needs of dental pulp repair and regeneration.
Emerging evidence suggests that growth factors are crucial in regenerative endodontic therapy. To achieve the desired effects, the systematic administration of supraphysiologic concentrations of exogenous growth factors is commonly performed, but this is usually associated with high costs, technique, and safety issues. Here, we describe a novel biomaterial that can manipulate endogenous growth factors without the need for adding exogenous growth factors. Transforming growth factor β1 binding peptide (TGFp) was grafted onto the surface of a neutral pH phytic acid–derived bioactive glass (PSC) to synthesize modified bioactive glass (PSC-TGFp). Fourier transform infrared spectroscopy and thermogravimetric analysis results demonstrated that the TGFp was successfully grafted to the surface of the PSC. Scanning electron microscopy and x-ray diffraction showed that PSC-TGFp possessed good in vitro bioactivity. After soaking in simulated body fluid for 24 h, hydroxyapatite formed on the surface of PSC-TGFp. Enzyme-linked immunosorbent assay showed that PSC-TGFp could capture endogenous transforming growth factor β1 from dentin matrix–extracted proteins (DMEP) and release it slowly over 21 d. Cytologic experiments revealed that PSC-TGFp after adsorbing DMEP could enhance the adhesion, migration, viability, and odontogenic differentiation of stem cells from apical papilla. The results highlight that PSC-TGFp may be a promising biomaterial to manipulate endogenous growth factors for regenerative endodontic therapy in the future.
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