Baicalin Inhibits Cell Proliferation and Inflammatory Cytokines Induced by Tumor Necrosis Factor α (TNF-α) in Human Immortalized Keratinocytes (HaCaT) Human Keratinocytes by Inhibiting the STAT3/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BACKGROUND Baicalin is a flavone isolated from the root of Scutellaria baicalensis and is used in traditional Chinese medicine. Psoriasis is a persistent and recurrent chronic inflammatory skin disease that is characterized by inflammation and increased proliferation of keratinocytes. This study aimed to investigate the effects of baicalin on HaCaT immortalized human keratinocytes in vitro and the molecular mechanisms involved. MATERIAL AND METHODS HaCaT keratinocytes were cultured in increasing concentrations of baicalin at 6.25 µM, 12.5 µM, and 25 µM. The in vitro model of psoriasis was established using HaCaT cells treated with tumor necrosis factor-alpha (TNF-alpha). The MTT assay was used to asses cell viability and apoptosis. Western blot was used to measure the expression of Bcl-2, Bax, pro-caspase-3, and cleaved caspase-3, and enzyme-linked immunosorbent assay (ELISA) was performed to detect inflammatory cytokines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of STAT3 and p65 mRNA. RESULTS Baicalin reduced cell viability and induced apoptosis of HaCaT human keratinocytes in a dose-dependent manner. Increased cell viability and the expression of inflammatory cytokines by HaCaT cells induced by TNF-alpha were significantly inhibited by baicalin. Baicalin significantly inhibited the activation of the STAT3/NF-kappaB pathway in HaCaT cells stimulated by TNF-alpha. CONCLUSIONS Baicalin inhibited the proliferation and expression of inflammatory cytokines in HaCaT immortalized human keratinocytes in vitro through the inhibition of the STAT3/NF-kappaB signaling pathway.

Dietary exposure assessment of a nursing mother-infant cohort to legacy and novel brominated flame retardants: Results of a 3-day duplicate diet study in Beijing, China.

In a 3-day duplicate diet study of a nursing mother-infant cohort (n = 20), the levels of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDD), and 5 novel brominated flame retardants (BFRs) were measured in 60 24-h duplicate diet samples and 20 breast milk samples provided by the mothers. The dietary BFR intake and related health risks of the mothers and their babies due to food consumption or human milk ingestion were subsequently assessed. At median concentrations of 284, 264 and 177 pg/g wet weight (ww) in the diet, decabrominated diphenyl ethers (BDE-209), decabromodiphenyl ethane (DBDPE) and HBCDD were predominant among the total BFRs. In human milk, HBCDD was the most abundant BFR, followed by BDE-209 and DBDPE, which indicates that BDE-209 and HBCDD have remained ubiquitous in the environment because of their continuous production and use in China. Meanwhile, concentrations of DBDPE were comparative to those of PBDEs and HBCDD in both diet and human milk, and DBDPE also had much higher concentrations than any other NBFRs, which indicates that the BFR consumption pattern in China is shifting from legacy BFRs to NBFRs. The median estimated dietary intakes (EDIs) of BDE-209, HBCDD and DBDPE for the mothers were 6.83, 3.73 and 5.44 ng/kg bw/day, respectively, and EDIs for their nursing babies were 24.7, 41.9 and 7.83 ng/kg bw/day, respectively. The nursing infants showed higher BFR body burden than the mothers. However, the EDIs obtained for both mothers and their babies discloses a low health risk to this mother-infant cohort.

Tetrabromobisphenol A, hexabromocyclododecane isomers and polybrominated diphenyl ethers in foodstuffs from Beijing, China: Contamination levels, dietary exposure and risk assessment.

Hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ether (PBDEs) are three legacy brominated flame retardants (BFRs); however, they are still produced and used in China. In this study, these three BFRs were measured in commonly consumed animal-based and plant-based foodstuffs from Beijing, China, and the dietary intakes of these BFRs by adults in Beijing were estimated to assess the related health concerns. The median levels of TBBPA in animal-based foodstuffs ranged from

Legacy and novel brominated flame retardants in indoor dust from Beijing, China: Occurrence, human exposure assessment and evidence for PBDEs replacement.

Levels of legacy brominated flame retardants (BFRs), including tetrabromobisphenol A (TBBPA), hexabromocyclododecane isomers (HBCDs) and polybrominated diphenyl ethers (PBDEs), and six currently used novel BFRs were determined in house dust and office dust collected from a community in Beijing, China. This is the first study where the three kinds of legacy BFRs and novel BFRs were all measured in dust samples from China. HPLC-MS/MS was used for the detection of TBBPA and HBCDs, and the other BFRs were tested on a GC-NCI/MS. Decabromodiphenyl ethane (DBDPE), PBDEs, HBCD and TBBPA were found to be the main BFRs in the dust samples, with median levels of 709, 241, 199 and 26.7ng/g dust, respectively. Due to the high density of electronic equipment used in offices, levels of BFRs in office dust were found to be higher than those in house dust. DBDPE, as a replacement of PBDEs, was the predominant BFR, and the median level of DBDPE was not only several orders of magnitude higher than that of other novel BFRs but also 3 to 27 times higher than that of the three legacy BFRs, indicating that the consumption pattern of BFRs in the Chinese market has shifted from PBDEs to PBDE alternatives. Median estimated daily intakes (EDIs) of BFRs through dust ingestion for adults (>20years) and toddlers (<2years) were in the range of 2.8×10-5-0.201ng/kg body weight (bw)/day and 5.7×10-4-2.52ng/kg bw/day, respectively. The body burden of BFRs for toddlers was far higher than that for adults; however, a comparison between EDIs and threshold values suggested that daily intakes of BFRs for both adults and toddlers were unlikely to raise significant health concerns.

New Insights into Mechanism of Molybdenum(VI)-Dioxo Complex Catalyzed Hydrosilylation of Carbonyls: An Alternative Model for Activating Si-H Bond.

Recently, a series of oxo/nitrido-Re(V)/Mo(VI)/Ru(VI)/Mn(V) complexes were demonstrated to be efficient catalysts in activating silanes and catalyzing hydrosilylations of unsaturated organic substrates. In the present study, the high-valent molybdenum(VI)-dioxo complex MoO2Cl2 catalyzed hydrosilylations of carbonyls was reinvestigated using density functional theory method. Previous experimental and theoretical investigations suggested a [2 + 2] addition pathway for MoO2Cl2 catalyzed hydrosilylations of ketones. In the present study, we propose an ionic outer-sphere mechanistic pathway to be the most favorable pathway. The key step in the ionic outer-sphere pathway is oxygen atom of C═O bonds nucleophilically attacking the silicon atom in an η(1)-silane molybdenum adduct. The Si-H bond is then cleaved heterolytically. This process features a novel SN2@Si transition state, which then generates a loosely bound ion pair: anionic molybdenum hydride paired with silylcarbenium ion ([MoO2Cl2H](-) [SiR3(OCR'R″)](+)) in solvent. The last step is silylcarbenium ion abstracting the hydride on molybdenum hydride to yield silyl ether. The calculated activation free energy barrier of the rate-determing step was 24.1 kcal/mol for diphenylketone (PhC═OPh) and silane of PhMe2SiH. Furthermore, the ionic outer-sphere pathway is calculated to be ∼10.0 kcal/mol lower than the previously proposed [2 + 2] addition pathway for a variety of silanes and aldehyde/ketone substrates. This preference arises from stronger electrophilicity of the high-valent molybdenum(VI) metal center toward a hydride. Here, we emphasize MoO2Cl2 behaves similar to Lewis acidic trispentafluorophenyl borane B(C6F5)3 in activating Si-H bond.

The unexpected mechanism underlying the high-valent mono-oxo-rhenium(V) hydride catalyzed hydrosilylation of C=N functionalities: insights from a DFT study.

In this study, we theoretically investigated the mechanism underlying the high-valent mono-oxo-rhenium(V) hydride Re(O)HCl2(PPh3)2 (1) catalyzed hydrosilylation of C=N functionalities. Our results suggest that an ionic S(N)2-Si outer-sphere pathway involving the heterolytic cleavage of the Si-H bond competes with the hydride pathway involving the C=N bond inserted into the Re-H bond for the rhenium hydride (1) catalyzed hydrosilylation of the less steric C=N functionalities (phenylmethanimine, PhCH=NH, and N-phenylbenzylideneimine, PhCH=NPh). The rate-determining free-energy barriers for the ionic outer-sphere pathway are calculated to be ∼28.1 and 27.6 kcal mol(-1), respectively. These values are slightly more favorable than those obtained for the hydride pathway (by ∼1-3 kcal mol(-1)), whereas for the large steric C=N functionality of N,1,1-tri(phenyl)methanimine (PhCPh=NPh), the ionic outer-sphere pathway (33.1 kcal mol(-1)) is more favorable than the hydride pathway by as much as 11.5 kcal mol(-1). Along the ionic outer-sphere pathway, neither the multiply bonded oxo ligand nor the inherent hydride moiety participate in the activation of the Si-H bond.

Concurrent extraction, clean-up, and analysis of polybrominated diphenyl ethers, hexabromocyclododecane isomers, and tetrabromobisphenol A in human milk and serum.

A method has been developed and validated for the concurrent extraction, clean-up, and analysis of polybrominated diphenyl ethers (PBDEs), α-, ß-, and γ-hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA) in human milk and serum. Milk and serum samples were extracted using accelerated solvent extraction with acetone/hexane 1:1, v/v and liquid-liquid extraction with methyl-tert-butyl ether/hexane 1:1, v/v, respectively. The removal of co-extracted biogenic materials was achieved by gel permeation chromatography followed by sulfuric acid treatment. The fractionation of the PBDEs and HBCD/TBBPA was performed using a Supelco LC-Si SPE cartridge. The detection of the PBDEs was then performed by GC-MS and that of the HBCDs and the TBBPA was performed using UPLC-MS/MS. The pretreatment procedure was optimized, and the characteristic ions and fragmentation of the analytes were studied by MS or MS/MS. A recovery test was performed using a matrix spiking test at concentrations of 0.05-10 ng/g. The recoveries ranged from 78.6-108.8% with RSDs equal to or lower than 14.04%. The LODs were 1.8-60 pg/g. The usefulness of the developed method was tested by the analysis of real human samples, and several brominated flame retardants in different samples were detected and analyzed.