NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of all-trans retinoic acid via targeting RDH16 in malignant glioma.

Polycomb group (PcG) proteins play an important role in development and stem cell maintenance, and their dysregulation have been closely linked to oncogenesis and cancer stem cell phenotypes. Here, we found that nervous system polycomb 1 (NSPc1) was highly expressed in stem cell-like glioma cells (SLCs). Knockdown of NSPc1 in SLCs resulted in impaired neurosphere formation and self-renewal abilities, down-regulated expression of stemness markers such as NESTIN, CD133 and SOX2, and decreased capacity to propagate subcutaneous xenografts. In contrast, glioma cells overexpressing NSPc1 exhibited a stem cell-like phenotype, up-regulated expression of stemness markers NESTIN, CD133 and SOX2, and an enhanced capacity to propagate subcutaneous xenografts. Furthermore, we identified that NSPc1 epigenetically repressed the expression of retinol dehydrogenase 16 (RDH16) by directly binding to a region upstream (-1073 to -823) of the RDH16 promoter. Next, we confirmed that RDH16 is a stemness suppressor that partially rescues SLCs from the NSPc1-induced increase in neurosphere formation. Finally, we showed that ATRA partly reversed the NSPc1-induced stemness enhancement in SLCs, through mechanisms correlated with an ATRA-dependent decrease in the expression of NSPc1. Thus, our results demonstrate that NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of ATRA via targeting RDH16 and may provide novel targets for glioma treatment in the future.

Synthesis of peptides of Carapax Trionycis and their inhibitory effects on TGF-ß1-induced hepatic stellate cells.

We previous identified the antifibrotic active ingredients from Carapax Trionycis as two peptides. Here, we synthesized these two peptides (peptide 1 and peptide 2) by a solid phase method and examined their effects on proliferation and activation of cultured hepatic stellate cells (HSC) which are the main ECM (extracellular matrix)-producing cells in fibrosis progression. We demonstrated that peptide 1 and peptide 2 significantly reduced HSC proliferation and activation in a dose dependent manner. Further, peptide 1 and peptide 2 could interfere with TGF-signaling by down-regulating Smad 3 phosphorylation. Thus, these synthetic peptides of Carapax Trionycis could inhibit proliferation and activation of HSC and might be used as a candidate for treatment of liver fibrosis.

Source seasonality of polycyclic aromatic hydrocarbons (PAHs) in a subtropical city, Guangzhou, South China.

Mega-cities are large sources of air pollution on a regional base. Differences in energy structures, geographical settings and regional climate features lead to a large variety of air pollution sources from place to place. To understand the seasonality of air pollution sources is critical to precise emission inventories and a sound protection of human health. Based on a year-round dataset, the sources of PAHs in the air of Guangzhou were drawn by principal factor analysis (PCA) in combination with diagnostic ratios, and the seasonality of these sources were analyzed by PCA/MLR (multiple linear regressions) and discussed. The average total gaseous and particulate PAHs concentrations were 313 and 23.7 ng m(-3), respectively, with a higher concentration of vapor PAHs in summer and particulate PAHs in winter. In addition to vehicle exhaust, which contributed 69% of the particulate PAHs, coal combustion was still an important source and contributed 31% of the particulate PAHs. Relatively constant contribution from coal combustion was found through the year, implying that coal combustion in power plants was not a seasonally dependent source. Evaporation from contaminated ground may be an important source of light PAHs in summer, providing an average contribution of 68% to the total PAHs in this study. By comparing the PAH concentrations and meteorological parameters, we found that higher concentrations of particulate PAHs in winter resulted from enhanced vehicle exhaust under low temperature and accumulation of pollutants under decreased boundary layer, slower wind speed, and long-term dryness conditions. It is suggested that the typical subtropical monsoon climate in South China, cool and dry in winter, hot and humid in summer, may play a key role in controlling the source seasonality (by enhancing vehicle exhaust in winter, ground evaporation in summer), and hence the ambient concentrations of PAHs in the air.

Sedimentary record of polycyclic aromatic hydrocarbons in a sediment core from the Pearl River Estuary, South China.

Owing to the hydrodynamic and sedimentation conditions, the western shoal of the Pearl River Estuary (PRE) is known to be an important sink of terrestrial substances including particle-associated pollutants from the Pearl River Delta (PRD) region. In this study, we report the sedimentary record of polycyclic aromatic hydrocarbons (PAHs) during the 20(th) century in a sediment core from the western shoal of the PRE. The summation PAH concentration ranged from 59 ng g(-1) to 330 ng g(-1) in the core with two distinct peaks. An initial increase of summation PAH concentration was found around the 1860s. The amounts of PAHs remained relatively constant for roughly 100 years, followed by the first peak in the 1950s. Then, there was a decrease in PAH concentration and flux in the 1960s and 1970s. A sharp increase of PAH concentration was observed in the early 1980s with a maximum concentration in the 1990s. The PAH diagnostic ratios indicated that the PAHs in the sediment core were mainly of pyrolytic origin, and that atmospheric deposition and land runoff may serve as the important pathways for PAHs input to the sediment. The Gross Domestic Product (GDP) was used as an index of socioeconomic development in the PRD region, which was correlated positively with the changes of PAH concentration and flux in the sediment core. The rapid increase in vehicle numbers and energy consumption in the region in the last two decades may have contributed to the rapid PAH increase since the early 1980s. The results clearly elucidated the impact of regional economic development on the estuarine environment.

[Bioinformatics analysis of autophagy 5 gene structure].

In order to study the relationship between autophagy and apoptosis, APG5 gene structure was revealed by bioinformatics analysis and meantime a new isoform resulted from alternative splicing of the hAPG5 gene was confirmed, which was hereby designated as human autophagy 5 beta (hAPG5 beta; LOCUS AF293841, GenBank). We cloned and sequenced the cDNAs from fetal brain and B cell cDNA libraries using the known hAPG5 cDNA open reading frame sequences as primers. The cDNA obtained from the human fetal brain cDNA library was identical to the known hAPG5 cDNA. However, the cDNA from adult brain cDNA library was 129 bp shorter in length, lacking the sequence corresponding to those from positions 434 to 563 of the hAPG5 cDNA. Through search in public database and sequence comparisons and assembly 4 related sequences, APG5 genomic sequence was obtained. We found that the hAPG5 gene had 8 exons, and those sequences missing in hAPG5 beta cDNA exactly corresponded to exon 3. By bioinformatics software, the structure of introns, exons, splicing sites, promoter and polyA were demonstrated. Moreover, we were able to express both hAGP5 and 5 beta cDNA clones in human hepatocytes and HeLa cells using pEGFP-C1 vector. In conclusion, our data indicate that a systematic bioinformatics method of finding protein diversity from alternative splicing is a good approach in post-genome biology.

[Activity of plasma dopamine-beta-hydroxylase and urine excretion of catecholamines in patients with deficiency-cold and deficiency-heat syndromes].

Spectrophotometric assay of plasma dopamine-beta-hydroxylase (D beta H) activity and fluorospectrophotometric assay of urine catecholamines (CA) were performed in 30 patients and 21 normal persons. According to TCM, the patients were divided into two groups, 16 cases of deficiency-cold syndrome (DCD), and 14 cases of deficiency-heat syndrome (DHD). The results showed that in the patients with DCD, the activity of D beta H and the levels of CA were lower than those of the normal, whereas the activity of D beta H and the levels of CA of the patients with DHD were higher than those of the normal (P less than 0.01, P less than 0.05). Variations of the involved visceral organs determined in the traditional way made no difference to the above-mentioned changes. D beta H and CA correlated significantly to each other. The authors also took the canonical correlation analysis to the cases, the result showed that the heat syndrome correlated with D beta H and CA positively. These results showed hyperfunctioning of the sympathetic-adrenomedullary system in DHD and hypofunctioning of this system in DCD.