NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis.

OBJECTIVE: This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM). METHODS: Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1ß) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM. RESULTS: The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1ß in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1ß as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1ß rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1ß blockade using neutralizing IL-1ß monoclonal antibody or siRNA of IL-1ß suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1ß and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum. CONCLUSION: NLRP3/caspase-1/IL-1ß axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM.

Establishment of Detection Methods for Five Cannabinoids in Hemp Cosmetics Based on HPLC.

A simultaneously HPLC detection method for cannabidiolic acid (CBDA), cannabidiol (CBD), cannabinol (CBN), Δ9-tetrahydrocannabinol (THC), tetrahydro-cannabinolic acid (THCA) in 3 kinds of cosmetics matrix containing hemp leaf extract was developed. The extraction and HPLC conditions were optimized, and a methodological verification was also carried out. The results showed that this method had a good linear relationship in the range of 0.25 - 50 µg/mL with LOD values for 5 cannabinoids all between 0.10 - 0.25 µg/g. The recovery rates of 5 cannabinoids in 3 different cosmetics matrixes were between 90.1 - 108.5%, and the RSD values were all below 4.4%. These results indicated that this method had the advantages of simple operation, high sensitivity, and good accuracy. Through the testing of 6 kinds of hemp cosmetics, it was found that such cosmetics had uneven quality. The establishment of this method can lay a methodological foundation for establishing relevant testing method standards.

[Distribution Characteristics and Health Risk Assessment of Heavy Metals in a Soil-Rice System in an E-waste Dismantling Area].

This study selected Guiyu Town, Guangdong Province as the research area, the content of 15 kinds of metals (As, Be, Cd, Co, Cr, Cu, Hg, Li, Mn, Ni, Sb, Sn, Pb, V, and Zn) in the soil was determined, and the content of heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the rice of this research area was identified. Multivariate statistical analysis and a human health risk assessment model were used to investigate the distribution characteristics and health risk of heavy metals in a soil-rice system. The results showed that Hg, Sb, and Sn in the surface soil surrounding the electronic waste dismantling area have obvious accumulation effect. The average content of Cd and Hg exceeds the Ⅱ standard limit of the "Environmental Quality Standard for Soil" (GB 156182-1995), and that Guiyu Town is more seriously polluted than Chendian Town and Simapu Town. The multivariate statistical analysis showed that Cu, Sb, Ni, Zn, Sn, Pb, and Hg originated from the surrounding electronic waste dismantling activities, Cd and Be originated from other man-made sources of pollution, and V, Li, Cr, Co, As, and Mn originated from natural sources. Heavy metal evaluation concentration in the soil-rice system by heavy metal migration accumulated in rice are in compliance with national food hygiene standards, and the enrichment ability is Cd > Zn > Cu > Ni > As > Cr > Hg > Pb. Soil heavy metal health risk assessment results showed that children are more susceptible to heavy metal pollution, and handling-oral ingestion is the main way of soil exposure risk. The non-carcinogenic risk and carcinogenic risk of heavy metals in the soil of each town are acceptable. The health risk in Guiyu Town through ingestion of rice is mainly from the elements that include As, Cr, Cu, and Ni.

[Seasonal Characteristics and Ecological Risk Assessment of Heavy Metals in PM10 Around Electroplating Plants].

PM10 samples were collected from 45 sites around the electroplating factories in five towns in Dongguan at different times during all four seasons in 2015. The contents of 12 heavy metals (HMs) from the PM10 samples were analyzed by ICP-MS. The seasonal and spatial distribution characteristics and the ecological risk were analyzed to provide a scientific foundation for the relevant department to make decisions regarding the environmental hazard, risk assessment and, pollution control. The results showed that PM10 concentrations in the towns were lower than national standard level-Ⅱ, and the air pollution was heavier in winter than summer. The HM concentrations were higher in autumn and winter, and As, Cd, and Cr concentrations were higher than national standard (GB3095-2012). The concentrations of HMs in Humen, Shatian, and Dalingshan were much higher. The results for the enrichment factor and the geoaccumulation index indicated that Cd, Sb, Hg, and Co were in the extreme degree of pollution category, Pb and Zn were in the slight to extreme degree of pollution category, and Ni, Cr, Mn, and V were described as uncontaminated. The average potential ecological risk assessment (RI) of the HMs from the PM10 samples was more than 600, which suggested an extremely serious ecological risk in the study area.

[Distribution Characteristics and Health Risk Assessment of Metals in Drinking Water Sources from the Luhun Reservoir].

In order to investigate the distribution characteristics and the human health risks of 12 metals in drinking water sources from the Luhun Reservoir, Al, As, Cd, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, and Zn concentrations in 46 water samples collected from the reservoir in 2016 were measured and analyzed. The health risks caused by metals were assessed by using a human health risk assessment model. The results showed that the maximum concentration of Al (200.27 µg·L-1) and all concentrations of Mo (151.42-170.69 µg·L-1) in drinking water from the Luhun Reservoir exceeded the Environmental Quality Standards for Surface Water (GB 3838-2002) and Standards for Drinking Water Quality (GB 5749-2006) by 4.35% and 100%, respectively. A distinct spatial heterogeneity was found in the metal distribution, and the region with the highest metals concentrations was located southwest (upstream) and northeast (downstream) of the reservoir. The results of a health risk assessment indicated that children had greater health risks than adults. The health risks for metals through drinking were all higher than the values caused by dermal contact. Carcinogenic risks caused by Cr and As exceeded the maximum allowance levels (5×10-5 a-1) by 100% and 3.80%, respectively, and Cr accounted for 85% of the total carcinogenic risks. The non-carcinogenic risks of the metals (10-12-10-7 a-1) decreased in the order of Al > Mo > Cu > Pb > Ni > Hg > Fe > Zn > Mn, which had levels two to seven orders of magnitude lower than the maximum allowance levels.

[Distribution Characteristics and Health Risk Assessment of Heavy Metals in Surface Water Around Electroplating Factories].

To investigate the distribution characteristics and the human health risks of heavy metals in surface water samples, 30 samples were collected around electroplating factories of Machong, Shatian, Humen, Changan and Dalingshan towns in Dongguan city, 8 heavy metals(As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) contents were measured and analyzed by using multivariate statistical analysis method and human health risk assessment model. The results showed that the maximum concentrations of Cr, Pb and the average concentration of Hg exceeded Environmental Quality Standards for Surface Water(GB 3838-2002, Grade Ⅲ), the concentrations of Cr, Cu, Hg, Ni, Zn and Pb during rainy season were all higher than that those during dry season. Multivariate statistical analysis indicated that Cd, Cr, Cu, Ni and Zn mainly originated from the contaminated electroplating factories, Pb and Hg were mainly affected by the traffic sources, and As was significantly correlated with natural sources. Health risk assessment result of surface water indicated that heavy metal pollution would lead to high health risks especially for children, and the health risks of heavy metals through drinking pathway were 2-3 orders of magnitude higher than the values caused by dermal contact pathway. Moreover, carcinogenic risks caused by Cr and As were higher than the maximum allowance levels (5×10-5 a-1), and non-carcinogenic risks of the heavy metals (10-10-10-7 a-1) decreased in the order of Pb > Ni > Cu > Hg > Zn, which were 4-5 orders of magnitude lower than the maximum allowance levels.