SD0006 promotes nucleus pulposus cell proliferation via the p38MAPK/HDAC4 pathway.

OBJECTIVE: p38 mitogen-activated protein kinase (p38MAPK) is a critical negative regulator for nucleus pulposus (NP) cell metabolism contributing to intervertebral disc degeneration (IDD). Histone deacetylase 4 (HDAC4) has the ability to mediate cell proliferation and is affected by p38MAPK. It is unclear whether the p38 MAPK inhibitor SD0006 (SD) can regulate IDD. Our study aims to explore the effect of SD in the progression of IDD, as well as its potential mechanism. PATIENTS AND METHODS: NP cells isolating from mild degenerated NP tissues were cultured, and IL-1ß or Asiatic acid (AA) was used to activate p38MAPK and accelerate the NP cell degradation. Then, SD was used to reject the p38MAPK activation. After that, the levels of phosphorylated p38MAPK (p-p38), HDAC4, proliferating cell nuclear antigen (PCNA), inflammatory factor, proliferative cell rate, and cell cycle were determined by Western blot, RT-PCR, flow cytometry, and immunofluorescence, respectively. RESULTS: The results showed that the activation of p38MAPK by IL-1ß and AA decreased the HDAC4 expression, affected the collagen-Ⅱ expression, upregulated the TNF-α, IL-6, MMP-3, and ADAMTS mRNA levels, and prevent the NP cell proliferation by mediating cell cycles. However, the application of SD alleviated the negative effect of p-p38 by upregulating HDAC4, anti-inflammation, and promoting cell proliferation, while the blocking of HDAC4 expression partly abolished the effect of SD. CONCLUSIONS: SD can prevent NP cell degeneration by promoting cell proliferation and suppressing inflammation via p38MAPK/HDAC4 pathway.

[Predictive value of upright blood pressure change for long-term prognosis of children with postural tachycardia syndrome treated with midodrine hydrochloride].

OBJECTIVE: To explore the predictive value of upright blood pressure change for long-term prognosis of children with postural tachycardia syndrome (POTS) treated with midodrine hydrochloride. METHOD: A total of 90 children (male 41, female 49) were enrolled in this study. Their mean age was (11.8±2.7) years. They were diagnosed as POTS in Peking University First Hospital from 2005 to 2011. According to the upright change of blood pressure at the first visit, they were divided into two groups, effective group (n=55) and ineffective group(n=35). The follow-up time was 53-130 months. The orthostatic intolerance symptom score and symptom free survival rate were compared between the two groups. RESULT: The change of systolic blood pressure and of diastolic blood pressure was lower in effective group than those in ineffective group (0(-6, 0) mmHg (1 mmHg=0.133 kPa) vs. 9(6, 11) mmHg, Z=-8.303, P<0.01; 0(0, 5) mmHg vs. 11(10, 16) mmHg, Z=-7.058, P<0.01). Two groups had no significant difference in symptom scores before treatment((4.8±0.9) points vs. (5.0±0.8) points, t=-0.53, P=0.595), while symptom scores were lower in effective group than that in ineffective group((1.3±0.9) points vs. (4.7±0.9) points, t=-15.60, P<0.01 ). The symptom free survival rate was higher in effective group than that in ineffective group (48/55(87.3%) vs. 23/35(65.7%), χ(2)=5.969, P<0.01). CONCLUSION: The upright change of blood pressure has a good predictive value on the long-term survival of POTS children treated with midodrine hydrochloride.

Spatiotemporal distribution of carbonyl compounds in China.

A sampling campaign was carried out at nine Chinese cities in 2010/2011. Fifteen monocarbonyls (C# = 1-9) were quantified. Temperature is the rate-determining factor of the summertime carbonyl levels. The carbonyl emissions in winter are mainly driven by the primary anthropogenic sources like automobile. A molar ratio of propionaldehyde to nonaldehyde is a barometer of the impact of atmospheric vegetation emission which suggesting that strong vegetation emissions exist in summer and high propionaldehyde abundance is caused by fossil fuel combustion in winter. Potential health risk assessment of formaldehyde and acetaldehyde was conducted and the highest cumulative risks were observed at Chengdu in summer and Wuhan in winter. Because of the strong photochemical reaction and large amount of anthropogenic emissions, high concentrations of carbonyl compounds were observed in Chengdu. The use of ethanol-blended gasoline in Wuhan is the key reason of acetaldehyde emission and action should be taken to avoid potential health risks.

Seasonal variations of monocarbonyl and dicarbonyl in urban and sub-urban sites of Xi'an, China.

Seventeen airborne carbonyls including monocarbonyls and dicarbonyls were determined in urban and sub-urban sites of Xi'an, China in three seasons in 2010. In winter, acetone was the most abundant carbonyl in the urban site due to usage of organic solvents in constructions and laboratories and its slower atmospheric removal mechanisms by photolysis and reaction with hydroxyl radical than those of formaldehyde and acetaldehyde. In the sub-urban site, acetaldehyde was the most abundant carbonyl, followed by formaldehyde and acetone. During summer, however, formaldehyde was the most dominant carbonyl in both sites. The photooxidations of a wide range of volatile organic compounds (VOCs) yielded much more formaldehyde than other carbonyls under high solar radiation and temperature. In the urban site, the average concentrations of dicarbonyls (i.e., glyoxal and methyglyoxal) in spring and summer were higher than that in winter. Transformation of aromatic VOCs emitted from fuel evaporation leads to the formation of 1,2-dicarbonyls. A reverse trend was observed in sub-urban sites, as explained by the relatively low abundances and accumulations of VOC precursors in the rural atmosphere during warm seasons. Moreover, cumulative cancer risk based on measured outdoor carbonyls (formaldehyde and acetaldehyde) in Xi'an Jiaotong University and Heihe was estimated (8.82 × 10(-5) and 4.96 × 10(-5), respectively). This study provides a clear map on the abundances of carbonyls and their source interpretation in the largest and the most economic city in Northwestern China.

Paradoxical role of autophagy in the dysplastic and tumor-forming stages of hepatocarcinoma development in rats.

Many reports have shown that autophagy has a role as both a promoter and inhibitor in tumor development. However, the mechanism of this paradox is unknown. Tumor development is a multistep process. Therefore, we investigated whether the role of autophagy in hepatocarcinoma formation depended on the stage of tumor development. Based on our results, autophagy inhibition by chloroquine had a tumor-promotive effect in the rat model with N-diethylnitrosamine-induced hepatocarcinogenesis in its dysplastic stage (Ds) and a tumor-suppressive effect in its tumor-forming stage (Ts). In the Ds, autophagy inhibition enhanced cell proliferation, DNA damage and inflammatory cytokines expression in liver. These changes were dependent on the upregulation of reactive oxygen species (ROS) that was resulted from autophagy inhibition, and ultimately accelerated the process of hepatocarcinogenesis. However, in the Ts, autophagy inhibition restrained tumor formation by decreasing tumor cell survival and proliferation. In this stage, autophagy inhibition led to excessive ROS accumulation in the tumor, which promoted cell apoptosis, and prominently suppressed tumor cell metabolism. Taken together, our data suggested that autophagy suppressed hepatocarcinogenesis in the Ds by protecting normal cell stability and promoted hepatocarcinogenesis in the Ts by supporting tumor cells growth. Autophagy always had a role as a protector throughout the process of hepatocarcinoma development.

Distribution of PBDEs in air particles from an electronic waste recycling site compared with Guangzhou and Hong Kong, South China.

Air samples of total suspended particles (TSP, particles less than 30-60 microm), and particles with aerodynamic diameter smaller than 2.5 microm (PM(2.5)) were collected simultaneously at Guiyu (an electronic waste recycling site), three urban sites in Hong Kong and two urban sites in Guangzhou, South China from 16 August to 17 September 2004. Twenty-two PBDE congeners (BDE-3, -7, -15, -17, -28, -49, -71, -47, -66, -77, -100, -119, -99, -85, -126, -154, -153, -138, -156, -184, -183, -191) in TSP and PM(2.5) were measured. The results showed that the overall average concentrations of TSP and PM(2.5) collected at Guiyu were 124 and 62.1 microg m(-3), respectively. The monthly concentrations of the sum of 22 BDE congeners contained in TSP and PM(2.5) at Guiyu were 21.5 and 16.6 ng m(-3), with 74.5 and 84.3%, contributed by nine congeners (BDE-28, -47, -66, -100, -99, -154, -153, -183 and -191 respectively). This pattern was similar to Tsuen Wan site of Hong Kong. Two urban sites of Guangzhou had the same congener pattern, but were different from Yuen Long and Hok Tsui sites of Hong Kong. The results also showed that the amount of mono to penta brominated congeners, which are more toxic, accounted for 79.4-95.6% of Sigma(22)PBDEs from all sites. All congeners tested in Guiyu were up to 58-691 times higher than the other urban sites and more than 100 times higher than other studies reported elsewhere. The higher concentration in the air was due to heating or opening burning of electronic waste since PBDEs are formed when plastics containing brominated flame retardants are heated.

Export of toxic chemicals - a review of the case of uncontrolled electronic-waste recycling.

This paper reviews the concentrations of persistent organic pollutants such as flame retardants (PBDEs), dioxins/furans (PCDD/Fs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and heavy metals/metalloid concentrations of different environmental media at Guiyu, a traditional rice-growing village located in southeastern Guangdong Province (PR China), which has turned into an intensive electronic-waste (e-waste) recycling site. Incomplete combustion of e-waste in open air and dumping of processed materials are the major sources of various toxic chemicals. By comparing with existing data available in other areas and also guidelines adopted in different countries, it is obvious that the environment is highly contaminated by these toxic chemicals derived from the recycling processes. For example, the monthly concentration of the sum of 22 PBDE congeners contained in PM(2.5) (16.8ngm(-3)) of air samples at Guiyu was 100 times higher than published data. In order to safeguard the environment and human health, detailed investigations are urgently needed, especially on tracking the exposure pathways of different toxic chemicals which may affect the workers and local residents especially mothers, infants and children.